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Sample records for leptin insulin glucose

  1. Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose

    Directory of Open Access Journals (Sweden)

    Tomomi Tsubai

    2016-11-01

    Conclusion: Insulin alone stimulates leptin secretion and elevates leptin mRNA levels via cAMP under the lack of glucose metabolism, while glucose is a significant and ambivalent effector on the insulin effects of leptin.

  2. Clinical significance of determination of serum leptin, insulin levels and blood sugar in pregnant women with glucose metabolism disturbances

    International Nuclear Information System (INIS)

    Yu Suqing; Li Yusheng; Wang Lin; Chu Kaiqiu

    2006-01-01

    Objective: To investigate the changes of serum leptin, insulin levels and blood sugar contents in pregnant women with gestational glucose metabolism disturbances. Methods: Fasting and 3h after oral 50g glucose serum levels of leptin were measured with RIA in 36 pregnant women with glucose metabolism disturbances (gestational diabetes mellitus or gestational impaired glucose tolerance) and 34 controls. Also, fasting serum insulin levels (with CLIA) and blood sugar contents 1h after oral 50 glucose (with glucose oxidase method) were determined in all these subjects. Results: 1. Serum levels of leptin in pregnant women with glucose metabolism disturbances were 14.9 ± 4.3 μg/L (vs controls 9.8 ± 1.7 μg/L, P<0.01). 2. The serum levels of insulin and 1 h post - 50g glucose blood sugar contents in pregnant women with glucose metabolism disturbances were 12.9±4.3mU/L and 11.0±1.4mmol/L respectively, which were both significantly positively correlated with the serum leptin levels (r=0.835, r=0.758 respectively) (vs levels in controls: 8.45±3.0mU/L and 7.84±1.3mmol/L). Conclusion: Elevation of fasting serum levels of leptin was demonstrated in pregnant women with glucose metabolism disturbances and the level of leptin was positively correlated with that of insulin and blood sugar. (authors)

  3. Pivotal role of leptin in insulin effects

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    R.B. Ceddia

    1998-06-01

    Full Text Available The OB protein, also known as leptin, is secreted by adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks regulating ingestive behavior and energy balance. The two forms of leptin receptors (long and short forms have been identified in various peripheral tissues, a fact that makes them possible target sites for a direct action of leptin. It has been shown that the OB protein interferes with insulin secretion from pancreatic islets, reduces insulin-stimulated glucose transport in adipocytes, and increases glucose transport, glycogen synthesis and fatty acid oxidation in skeletal muscle. Under normoglycemic and normoinsulinemic conditions, leptin seems to shift the flux of metabolites from adipose tissue to skeletal muscle. This may function as a peripheral mechanism that helps control body weight and prevents obesity. Data that substantiate this hypothesis are presented in this review.

  4. Serum leptin and insulin tests in obesity

    International Nuclear Information System (INIS)

    Yang Yin; Jiang Xiaojin; Leng Xiumei

    2001-01-01

    Objective: To study the clinical significance and the relations of leptin and insulin on obesity group. Methods: Leptin and insulin were tested with radioimmunoassay (RIA) in pre-obesity group and obesity group respectively. Results: Serum leptin and insulin levels were significantly elevated in obesity group compare with the controls (P<0.01). Conclusion: Changing with insulin, the elevation of leptin in obesity group has been identified as an important agent of diabetes mellitus (DM)

  5. Leptin responses to bovine interferon- α and insulin in cattle

    African Journals Online (AJOL)

    Egyptian Journal of Biochemistry and Molecular Biology ... IFN- α injection produced a rapid increase in glucose and insulin levels but leptin levels did not show any alteration after the injection. ... Insulin levels rapidly increased in the blood and consequently a significant decrease in blood glucose level was recorded.

  6. Metabolic health assessment of zoo elephants: Management factors predicting leptin levels and the glucose-to-insulin ratio and their associations with health parameters.

    Directory of Open Access Journals (Sweden)

    Kari A Morfeld

    Full Text Available Screening for metabolic-related health problems can enhance animal welfare, so the purpose of this study was to conduct the first metabolic health assessment of zoo elephants and use epidemiological methods to determine how factors in the captive environment were associated with metabolic hormone concentrations. In addition, we examined relationships between metabolic status and several fitness parameters: foot health, musculoskeletal health, reproductive cyclicity, and body condition. Two blood samples were collected 2 weeks apart from 87 Asian (Elephas maximus and 105 African (Loxodonta africana elephants managed by zoos accredited by the Association of Zoos and Aquariums for analysis of serum leptin, insulin, glucose and the glucose-to-insulin ratio (G:I. In females, mean (± SD leptin concentrations and the G:I were lower (P0.05. As mean leptin concentration increased there was an increase in the odds of a female being non-cycling (P = 0.0083. The G:I was associated inversely with body condition (P = 0.0002; as the G:I increased there was a decreased risk of BCS = 4 or 5 as compared to the ideal, or BCS = 3. Neither leptin nor G:I were predictive of foot or musculoskeletal health scores. Factors related to walking and feeding practices were most influential in predicting metabolic status, whereas social and housing factors showed smaller, but significant effects. The metabolic health benefits of walking were detected if the time spent in staff-directed walking was 7 hours or more per week. The most protective feeding practices included implementing a random rather than predictable feeding schedule and limiting the number of methods presentation methods. Results indicate that leptin levels and G:I can be used as predictors of both ovarian cycle function and body condition, and are affected by zoo management in elephants.

  7. Relationship of insulin, glucose, leptin, IL-6 and TNF-α in human breast-milk with infant growth and body composition

    OpenAIRE

    Fields, David A; Demerath, Ellen W.

    2012-01-01

    Numerous appetite, growth, obesity-related hormones and inflammatory factors are found in human breast-milk, but there is little evidence on their relationship with infant body composition. The purpose of the present cross-sectional pilot study was to assess the cross-sectional associations of appetite-regulating hormones and growth factors (leptin, insulin, glucose) and inflammatory factors (IL-6 and TNF-α) in human breast-milk with infant size, adiposity, and lean tissue at 1-month of age i...

  8. Metabolic health assessment of zoo elephants: Management factors predicting leptin levels and the glucose-to-insulin ratio and their associations with health parameters.

    Science.gov (United States)

    Morfeld, Kari A; Brown, Janine L

    2017-01-01

    Screening for metabolic-related health problems can enhance animal welfare, so the purpose of this study was to conduct the first metabolic health assessment of zoo elephants and use epidemiological methods to determine how factors in the captive environment were associated with metabolic hormone concentrations. In addition, we examined relationships between metabolic status and several fitness parameters: foot health, musculoskeletal health, reproductive cyclicity, and body condition. Two blood samples were collected 2 weeks apart from 87 Asian (Elephas maximus) and 105 African (Loxodonta africana) elephants managed by zoos accredited by the Association of Zoos and Aquariums for analysis of serum leptin, insulin, glucose and the glucose-to-insulin ratio (G:I). In females, mean (± SD) leptin concentrations and the G:I were lower (Pelephants, respectively. For males, mean leptin and the G:I were 4.99 ± 3.61 ng/ml and 253 ± 181 units for Asian, and 3.72 ± 2.00 ng/ml and 326 ± 231 units for African elephants, respectively, with no differences between species (P>0.05). As mean leptin concentration increased there was an increase in the odds of a female being non-cycling (P = 0.0083). The G:I was associated inversely with body condition (P = 0.0002); as the G:I increased there was a decreased risk of BCS = 4 or 5 as compared to the ideal, or BCS = 3. Neither leptin nor G:I were predictive of foot or musculoskeletal health scores. Factors related to walking and feeding practices were most influential in predicting metabolic status, whereas social and housing factors showed smaller, but significant effects. The metabolic health benefits of walking were detected if the time spent in staff-directed walking was 7 hours or more per week. The most protective feeding practices included implementing a random rather than predictable feeding schedule and limiting the number of methods presentation methods. Results indicate that leptin levels and G:I can be used as predictors

  9. Relationship of insulin, glucose, leptin, IL-6 and TNF-α in human breast milk with infant growth and body composition.

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    Fields, D A; Demerath, E W

    2012-08-01

    Numerous appetite, growth, obesity-related hormones and inflammatory factors are found in human breast-milk, but there is little evidence on their relationship with infant body composition. OBJECTVIE: The purpose of the present cross-sectional pilot study was to assess the cross-sectional associations of appetite-regulating hormones and growth factors (leptin, insulin and glucose) and inflammatory factors (interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) in human breast-milk with infant size, adiposity, and lean tissue at 1-month of age in healthy term infants. Human breast-milk was collected from nineteen exclusively breast-feeding mothers using one full breast expression between 8:00 and 10:00 a.m. The milk was then mixed, aliquoted, stored at -80°C and then centrifuged to remove the milk fat, prior to analyses using commercially available immunoassay kits; milk analytes were natural log transformed prior to analysis. Infant body composition was assessed using a Lunar iDXA v11-30.062 scanner (Infant whole body analysis enCore 2007 software, GE, Fairfield, CT). Maternal pre-pregnancy BMI was positively associated with milk leptin concentration (P = 0.0027), and so maternal-BMI-adjusted Spearman correlations were examined between breast-milk analytes and infant growth and body composition variables. As previously reported, greater milk leptin was associated with lower BMIZ (BMI-for-age z-score based on WHO 2006 growth charts; r = -0.54, P = 0.03). Glucose was positively associated with relative weight (r = 0.6, P = 0.01), and both fat and lean mass (0.43-0.44, P milk insulin were associated with lower infant weight, relative weight, and lean mass (r = -0.49-0.58, P milk IL-6 was associated with lower relative weight, weight gain, percent fat, and fat mass (r = -0.55-0.70, P milk concentrations of insulin, glucose, IL-6 and TNF-α, in addition to leptin, may be bioactive and differentially influence the accrual of fat and lean body mass. © 2012

  10. Relationship of insulin, glucose, leptin, IL-6 and TNF-α in human breast-milk with infant growth and body composition

    Science.gov (United States)

    Fields, David A; Demerath, Ellen W.

    2012-01-01

    Numerous appetite, growth, obesity-related hormones and inflammatory factors are found in human breast-milk, but there is little evidence on their relationship with infant body composition. The purpose of the present cross-sectional pilot study was to assess the cross-sectional associations of appetite-regulating hormones and growth factors (leptin, insulin, glucose) and inflammatory factors (IL-6 and TNF-α) in human breast-milk with infant size, adiposity, and lean tissue at 1-month of age in healthy term infants. Human breast-milk was collected from nineteen exclusively breast-feeding mothers using one full breast expression between 8:00 and 10:00 am. The milk was then mixed, aliquoted, stored at −80°C and then centrifuged to remove the milk fat, prior to analyses using commercially available immunoassay kits; milk analytes were natural log transformed prior to analysis. Infant body composition was assessed using a Lunar iDXA v11-30.062 scanner (Infant whole body analysis enCore 2007 software, GE, Fairfield, CT). Maternal pre-pregnancy BMI was positively associated with milk leptin concentration (p=0.0027), and so maternal-BMI-adjusted Spearman correlations were examined between breast-milk analytes and infant growth and body composition variables. As previously reported, greater milk leptin was associated with lower BMIZ (r= −0.54, p=0.03). Glucose was positively associated with relateive weight (r = 0.6, p=0.01), and both fat and lean mass (0.43 – 0.44, pmilk insulin were associated with lower infant weight, relative weight, and lean mass (r = −0.49 – 0.58, pmilk IL-6 was associated with lower relative weight, weight gain, percent fat, and fat mass (r = −0.55 – 0.70, pmilk concentrations of insulin, glucose, IL-6 and TNF-α, in addition to leptin, may be bioactive and differentially influence the accrual of fat and lean body mass. PMID:22577092

  11. INFLUENCE OF DIETARY FAT ON LEPTIN AND INSULIN IN MALE ALBINO RATS

    International Nuclear Information System (INIS)

    KASSAB, F.M.A.; ABDEL-KHALEK, L.G.; KAMAL, A.M.

    2008-01-01

    Sixty male albino rats were arranged into 5 equal groups which were used in this study to investigate the relation between leptin and insulin hormones under high fat intake and to assess the role of fresh vegetable intake on minimizing dyslipidemia.The results denoted that dietary fat caused significant increase in the levels of blood glucose and leptin hormone with significant decrease in insulin concentration and with prolonged high fat intake, insulin level was increased. However, the increased leptin and glucose indicated that prolonged fatty diet may cause insulin resistance. Addition of green vegetables to the diet normalized to a great extent the level of cholesterol, triglycerides, VLDL, glucose and insulin

  12. Leptin, adiponectin, leptin to adiponectin ratio and insulin resistance in depressive women.

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    Zeman, Miroslav; Jirak, Roman; Jachymova, Marie; Vecka, Marek; Tvrzicka, Eva; Zak, Ales

    2009-01-01

    Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested, that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistence (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated fasting glycaemia, could stand behind the connection. Recent findings have shown, that adipocytokines leptin and adiponectin might play a role in both depression and MetS. The aim of this pilot study was to observe the plasma concentrations of leptin, adiponectin, leptin-to-adiponectin ratio and indices of IR in women with depressive disorder. The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in a group of 38 women with DD. The results were compared with those of 38 healthy women of the control group, matched for age. Depressive women differed significantly from the controls in higher concentrations of plasma leptin (p DM2 or CVD.

  13. Effect of vanadium on insulin and leptin in Zucker diabetic fatty rats.

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    Wang, J; Yuen, V G; McNeill, J H

    2001-02-01

    Vanadium exhibits a variety of insulin-mimetic actions in vitro and in vivo. The mechanism(s) of the effect of vanadium on leptin in Zucker diabetic fatty (ZDF) rats, a model of Type 2 diabetes, is unclear. Since insulin is a stimulator of leptin production and secretion and vanadium is an insulin-mimetic or insulin-enhancing agent, we studied how vanadium affected plasma leptin levels in vivo and the relationship between plasma insulin, leptin and body fat in ZDF rats. Zucker lean and ZDF rats at 9-week old were chronically treated with bis(ethylmaltolato)oxovanadium(IV) (BEOV), an organic vanadium compound, by oral gavage daily for 3 weeks. At termination, the total body fat was weighed and blood was collected for insulin, leptin and glucose assay. BEOV treatment (0.1 mmol/kg/day) significantly decreased plasma glucose levels in ZDF rats and did not change food intake and body fat content either in lean or ZDF rats. Following 3-week treatment, plasma insulin and leptin levels in BEOV treated ZDF rats were significantly higher, 1.5 and 0.5 fold than untreated rats, respectively. The correlation coefficients in ZDF rats showed that plasma leptin levels were correlated to plasma insulin levels, but not to body fat. These data indicate that plasma leptin levels parallel plasma insulin levels, and the effects of vanadium on leptin appear to be mediated by insulin in ZDF rats.

  14. Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance

    NARCIS (Netherlands)

    Connelly, Margery A.; Wolak-Dinsmore, Justyna; Dullaart, Robin P. F.

    Background: Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the

  15. Leptin and insulin signaling in dopaminergic neurons: relationship between energy balance and reward system.

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    Khanh, Doan V; Choi, Yun-Hee; Moh, Sang Hyun; Kinyua, Ann W; Kim, Ki Woo

    2014-01-01

    The central actions of leptin and insulin are essential for the regulation of energy and glucose homeostasis. In addition to the crucial effects on the hypothalamus, emerging evidence suggests that the leptin and insulin signaling can act on other brain regions to mediate the reward value of nutrients. Recent studies have indicated the midbrain dopaminergic neurons as a potential site for leptin' and insulin's actions on mediating the feeding behaviors and therefore affecting the energy balance. Although molecular details about the integrative roles of leptin and insulin in this subset of neurons remain to be investigated, substantial body of evidence by far imply that the signaling pathways regulated by leptin and insulin may play an essential role in the regulation of energy balance through the control of food-associated reward. This review therefore describes the convergence of energy regulation and reward system, particularly focusing on leptin and insulin signaling in the midbrain dopaminergic neurons.

  16. Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study

    DEFF Research Database (Denmark)

    Donahue, R P; Prineas, R J; Donahue, R D

    1999-01-01

    Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic m...

  17. Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study

    DEFF Research Database (Denmark)

    Donahue, R P; Prineas, R J; Donahue, R D

    1999-01-01

    Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic men...

  18. Comparative acute effects of leptin and insulin on gluconeogenesis and ketogenesis in perfused rat liver.

    Science.gov (United States)

    Borba-Murad, Glaucia Regina; Mario, Erica Guilhen; Bassoli, Bruna Kempfer; Bazotte, Roberto Barbosa; de Souza, Helenir Medri

    2005-01-01

    The acute effects of physiological levels of leptin (10 ng ml(-1)) and insulin (20 microU ml(-1)) on hepatic gluconeogenesis and ketogenesis were compared. Leptin or insulin alone decreased (p<0.05) the activation of hepatic glucose, L-lactate and urea production from L-alanine. However, the hepatic glucose production was not modified if leptin was combined with insulin. These results indicated that both, i.e. leptin and insulin, could promote a non-additive reduction in the rate of catabolism of L-alanine. However, in contrast with insulin (p<0.05), leptin did not inhibit the activation of hepatic glucose production from pyruvate or glycerol. On the other hand, activation of hepatic production of acetoacetate and beta-hydroxybutyrate from octanoate was not affected by leptin or insulin. Thus, our data demonstrate that the acute effect of leptin on hepatic metabolism was partially similar to insulin (activation of glucose production from L-alanine and activation of acetoacetate or beta-hydroxybutyrate production from octanoate) and partially different from insulin (activation of glucose production from pyruvate or glycerol). Copyright (c) 2004 John Wiley & Sons, Ltd.

  19. Leptin recruits Creb-regulated transcriptional coactivator 1 to improve hyperglycemia in insulin-deficient diabetes

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    Geun Hyang Kim

    2015-03-01

    Conclusions: Our study reveals that Crtc1 functions as a conduit for leptin's glucoregulatory actions in insulin-dependent diabetes. This study also highlights a new role for Crtc1 in modulating peripheral glucose metabolism.

  20. Some metabolic and anthropometric variables in obes children by measuring serum insulin, and leptin

    International Nuclear Information System (INIS)

    Nour Eldin, A.M.

    2004-01-01

    The present study aimed to assess serum leptin level in obese children to study its correlation with some metabolic variables as serum insulin and serum glucose. The study was conducted on 30 obese children of age from 9-14 years with body mass index (BMI) > 27.8 Kg/m 2 . All children were subjected to history taking, clinical examination, anthropometric measurements and laboratory investigations including fasting serum leptin, insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml) compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric measurements and laboratory investigations including fasting serum insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml)compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric variables was positively correlated with BMI r s = 0.68, (p s = 0.59.(p<0.01). It is concluded that serum leptin is increased in obesity and its concentration effects the size of the body. Moreover, the relation of leptin and insulin suggests a positive role of leptin in insulin resistance, which are common metabolic disorders associated with obesity

  1. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study.

    Science.gov (United States)

    Zimmet, P; Hodge, A; Nicolson, M; Staten, M; de Courten, M; Moore, J; Morawiecki, A; Lubina, J; Collier, G; Alberti, G; Dowse, G

    1996-10-19

    To measure serum leptin concentrations in the Polynesian population of Western Samoa and to examine epidemiological associations of leptin with anthropometric, demographic, behavioural, and metabolic factors in this population with a high prevalence of obesity and non-insulin dependent diabetes mellitus. Cross sectional study, leptin concentration being measured in a subgroup of a population based sample. 240 Polynesian men and women aged 28-74 years were selected to cover the full range of age, body mass index, and glucose tolerance. Serum leptin, insulin, and glucose concentrations; anthropometric measures; physical activity; and area of residence. Leptin concentrations were correlated with body mass index (r = 0.80 in men, 0.79 in women) and waist circumference (r = 0.82 in men, 0.78 in women) but less so with waist to hip ratio. At any body mass index, leptin concentration was higher in women than men (geometric mean adjusted for body mass index 15.3 v 3.6 pg/l, P < 0.001). Leptin concentration also correlated with fasting insulin concentration (r = 0.63 in men, 0.64 in women) and insulin concentration 2 hours after a glucose load (r = 0.58 in men, 0.52 in women). These associations remained significant after controlling for body mass index; effects of physical activity and of rural or urban living on leptin concentration were eliminated after adjusting for obesity, except values remained high in urban men. 78% of variance in leptin was explained by a model including fasting insulin concentration, sex, body mass index, and a body mass index by sex interaction term. Similar results were obtained if waist circumference replaced body mass index. The strong relation of leptin with obesity is consistent with leptin production being proportional of mass to adipose tissue. The relation with insulin independent of body mass index suggests a possible role for leptin in insulin resistance or hyperinsulinaemia.

  2. Increased plasma leptin through l-carnitine supplementation is associated with an enhanced glucose tolerance in healthy ponies.

    Science.gov (United States)

    Van Weyenberg, S; Buyse, J; Janssens, G P J

    2009-04-01

    In this study 0 or 4 g of l-carnitine was supplemented for 7 days in a cross-over design of six healthy ponies to modulate glucose metabolism and leptin production. At the end of each period, serial blood samples were taken to measure glucose and insulin response, leptin, triglyceride (TG), non-esterified fatty acids (NEFA) and creatine phosphokinase. l-carnitine supplementation was associated with a decrease in postprandial plasma glucose and insulin concentration, indicating an enhanced glucose tolerance. In contrast, postprandial plasma leptin concentration was increased when l-carnitine was supplemented. Yet, this increase in leptin concentration was not preceded by an increase in insulin concentration, suggesting that other factors apart from plasma insulin concentration could influence plasma leptin concentration. Although NEFA and TG were not significantly influenced by l-carnitine supplementation under these experimental conditions, further research must clarify whether net TG synthesis might be responsible for this increase in leptin.

  3. A ketogenic diet impairs energy and glucose homeostasis by the attenuation of hypothalamic leptin signaling and hepatic insulin signaling in a rat model of non-obese type 2 diabetes.

    Science.gov (United States)

    Park, Sunmin; Kim, Da Sol; Kang, Sunna; Daily, James W

    2011-02-01

    Ketogenic diets (KTD) are reported to have beneficial effects on the regulation of energy and glucose homeostasis, but remain controversial. We investigated the effects of KTD and ketones on insulin resistance and secretion in non-obese type 2 diabetic rats and their mechanism. KTD (82% energy as fat), intraperitoneal injection of β-hydroxybutyrate (IHB; 150 mg/kg bw/12 h) with a control diet (COD; 20% energy as fat) or saline injection with COD was given to 90% pancreatectomized (Px) diabetic rats for five weeks. KTD increased epididymal fat pads and serum leptin levels without increasing energy intake, but IHB decreased them. KTD, but not IHB, attenuated hypothalamic signal transducer and activator of transcription 3 and 5'-adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in KTD. Serum glucagon levels were markedly higher in the KTD group than in other groups. During an oral glucose tolerance test, serum glucose levels slowly increased until 80 min in the KTD group and then decreased very slowly. Insulin secretion capacity during a hyperglycemic clamp was significantly lower in the IHB group than in other groups. However, a euglycemic hyperinsulinemic clamp revealed that KTD decreased glucose infusion rates and increased hepatic glucose output in hyperinsulinemic states while IHB had opposite effects to KTD. The increased hepatic glucose output in KTD was associated with increased hepatic phosphoenolpyruvate carboxykinase expression through attenuated tyrosine phosphorylation of IRS2 and phosphorylation of Akt(Ser473). Hepatic AMPK(Thr172) phosphorylation was reduced in KTD. In conclusion, KTD impairs energy and glucose homeostasis by exacerbating insulin resistance and attenuating hypothalamic leptin signaling in non-obese type 2 diabetic rats. These changes are not associated with increased serum ketone levels.

  4. Mechanism for leptin's acute insulin-independent effect to reverse diabetic ketoacidosis.

    Science.gov (United States)

    Perry, Rachel J; Peng, Liang; Abulizi, Abudukadier; Kennedy, Lynn; Cline, Gary W; Shulman, Gerald I

    2017-02-01

    The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown. We examined the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced rat model of DKA. Leptin infusion reduced rates of lipolysis, hepatic glucose production (HGP), and hepatic ketogenesis by 50% within 6 hours and were independent of any changes in plasma glucagon concentrations; these effects were abrogated by coinfusion of corticosterone. Treating leptin- and corticosterone-infused rats with an adipose triglyceride lipase inhibitor blocked corticosterone-induced increases in plasma glucose concentrations and rates of HGP and ketogenesis. Similarly, adrenalectomized type 1 diabetic (T1D) rats exhibited decreased rates of lipolysis, HGP, and ketogenesis; these effects were reversed by corticosterone infusion. Leptin-induced decreases in lipolysis, HGP, and ketogenesis in DKA were also nullified by relatively small increases (15 to 70 pM) in plasma insulin concentrations. In contrast, the chronic glucose-lowering effect of leptin in a STZ-induced mouse model of poorly controlled T1D was associated with decreased food intake, reduced plasma glucagon and corticosterone concentrations, and decreased ectopic lipid (triacylglycerol/diacylglycerol) content in liver and muscle. Collectively, these studies demonstrate marked differences in the acute insulin-independent effects by which leptin reverses fasting hyperglycemia and ketoacidosis in a rodent model of DKA versus the chronic pleotropic effects by which leptin reverses hyperglycemia in a non-DKA rodent model of T1D.

  5. Insulin and Leptin Signaling Interact in the Mouse Kiss1 Neuron during the Peripubertal Period.

    Directory of Open Access Journals (Sweden)

    Xiaoliang Qiu

    Full Text Available Reproduction requires adequate energy stores for parents and offspring to survive. Kiss1 neurons, which are essential for fertility, have the potential to serve as the central sensors of metabolic factors that signal to the reproductive axis the presence of stored calories. Paradoxically, obesity is often accompanied by infertility. Despite excess circulating levels of insulin and leptin, obese individuals exhibit resistance to both metabolic factors in many neuron types. Thus, resistance to insulin or leptin in Kiss1 neurons could lead to infertility. Single deletion of the receptors for either insulin or the adipokine leptin from Kiss1 neurons does not impair adult reproductive dysfunction. However, insulin and leptin signaling pathways may interact in such a way as to obscure their individual functions. We hypothesized that in the presence of genetic or obesity-induced concurrent insulin and leptin resistance, Kiss1 neurons would be unable to maintain reproductive function. We therefore induced a chronic hyperinsulinemic and hyperleptinemic state in mice lacking insulin receptors in Kiss1 neurons through high fat feeding and examined the impact on fertility. In an additional, genetic model, we ablated both leptin and insulin signaling in Kiss1 neurons (IR/LepRKiss mice. Counter to our hypothesis, we found that the addition of leptin insensitivity did not alter the reproductive phenotype of IRKiss mice. We also found that weight gain, body composition, glucose and insulin tolerance were normal in mice of both genders. Nonetheless, leptin and insulin receptor deletion altered pubertal timing as well as LH and FSH levels in mid-puberty in a reciprocal manner. Our results confirm that Kiss1 neurons do not directly mediate the critical role that insulin and leptin play in reproduction. However, during puberty kisspeptin neurons may experience a critical window of susceptibility to the influence of metabolic factors that can modify the onset of

  6. Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice.

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    Mokadem, Mohamad; Zechner, Juliet F; Uchida, Aki; Aguirre, Vincent

    2015-01-01

    Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB) induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB. To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet. RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.

  7. Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice.

    Directory of Open Access Journals (Sweden)

    Mohamad Mokadem

    Full Text Available Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB.To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet.RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.

  8. Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort.

    Science.gov (United States)

    Leisegang, Kristian; Bouic, Patrick J D; Menkveld, Roelof; Henkel, Ralf R

    2014-05-07

    Obesity appears to be associated with male reproductive dysfunction and infertility, although this has been inconsistent and inconclusive. Insulin and leptin are known mediators and modulators of the hypothalamus-pituitary-testes axis, contributing to the regulation of male reproductive potential and overall wellbeing. These hormones are also present in semen influencing sperm functions. Although abdominal obesity is closely associated with insulin resistance (hyperinsulinaemia), hyperleptinaemia and glucose dysfunction, changes in seminal plasma concentrations of insulin, leptin and glucose in obese males has not previously been investigated. This small case controlled study assessed serum and seminal concentrations of insulin, leptin and glucose in obese (BMI > =30; n = 23) and non-obese (BMI Obesity was associated with increased serum and seminal insulin and leptin, with no significant difference in seminal glucose. Serum and seminal concentrations of insulin and leptin were positively correlated. Furthermore, obesity was associated with decreased sperm concentration, sperm vitality and increased MMP and DF, with a non-significant impact on motility and morphology. Hyperinsulinaemia and hyperleptinaemia are associated with increased seminal insulin and leptin concentrations, which may negatively impact male reproductive function in obesity. Insulin was also found to be highly concentrated in the seminal plasma of both groups. This data will contribute to the contradictive information available in the literature on the impact of obesity and male reproduction.

  9. Leptin-induced basal Akt phosphorylation and its implication in exercise-mediated improvement of insulin sensitivity.

    Science.gov (United States)

    Zheng, Xianjie; Niu, Sen

    2018-01-29

    Physical exercise is an efficient therapeutical tool in the management of insulin resistance (IR) and related metabolic diseases. Leptin, the well-known obesity hormone and the absence of which leads to IR, showed controversial effects on IR as research continues. Thus, in this study, a detailed investigation of the effect of leptin on exercise-mediated improvement of insulin sensitivity and its underlying mechanism was carried out. Using a rat model of chronic or acute swimming exercise training, we found that serum leptin increased 1 h after either acute exercise or the last session of chronic exercise, when impaired insulin action was observed in previous reports. However, chronic exercise reducd basal serum leptin levels and promoted insulin sensitivity compared with sedentary controls or rats subjected to one bout of aerobic exercise. Our animal results indicated the potential linkage between leptin and insulin sensitivity, which is further investigated in the skeletal muscle L6 cells. Leptin treatment in L6 cells promoted the basal levels of insulin signaling as well as glucose uptake, while blocking JAK2 signaling with either pharmacological intervention (JAK2 inhibitor AG490) or genetic manipulation (siRNA knockdown) decreased the basal levels of insulin signaling. Furthermore, leptin treatment inhibited insulin-stimulated insulin signaling and glucose uptake, while blocking JAK2 signaling restored leptin-attenuated insulin sensitivity. Taken together, our results demonstrated that reduced serum leptin, at least in part, contributes to exercise-mediated improvement of insulin sensitivity, indicating JAK2 as a potent therapeutical target of insulin resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Should leptin replace insulin as a lifetime monotherapy for diabetes type 1 and 2?

    Directory of Open Access Journals (Sweden)

    Satya P Kalra

    2013-01-01

    Full Text Available Evidence accumulated during the last decade has affirmed that adipocyte leptin insufficiency in the hypothalamus is the primary etiological factor in the pathogenesis of diabetes type 1 and 2 and related metabolic morbidities. Leptin insufficiency disrupts the relay of hypothalamic regulatory information along three descending pathways to the organs in the periphery that normally participate in maintenance of glucose homeostasis on a minute-to-minute basis throughout lifetime. Reinstatement of leptin sufficiency in the hypothalamus by either systemic or central injections, or its provision selectively in the hypothalamus with the aid of gene therapy extinguished hyperglycemia and normalized blood glucose stably during the entire course of treatment in a variety of animal models of diabetes type 1 and 2. In follow-up clinical trials, twice daily leptin treatment in leptinopenic and insulinopenic type 1 diabetics and leptinopenic and hyperinsulinemic type 2 diabetics with congenital lipodystrophy or acquired lipoatrophy normalized blood glucose without any discernible adverse effects during the extended course of treatment. Taken together, these findings have amply endorsed the efficacy of leptin therapy to restore glucose homeostasis in insulin-deficient as well as hyperinsulinemic diabetic patients. Consequently, restoration of optimal hypothalmic signaling to reinstate glucose homeostasis with leptin is a highly suitable new therapeutic strategy to ameliorate diabetes type 1 and 2 for the lifetime and to replace the currently in vogue insulin monotherapy. In view of the relentless challenges posed by the worldwide epidemic of diabetes and soaring treatment costs, taken together with the well-known shortcomings of therapies based on restoring insulin signaling, it is highly critical and timely to undertake new clinical trials that ascertain appropriate dosage and route of leptin delivery to the hypothalamus capable of safely sustaining stable

  11. Association of leptin and insulin resistance in PCOS: A case-controlled study.

    Science.gov (United States)

    Namavar Jahromi, Bahia; Dabaghmanesh, Mohammad Hassan; Parsanezhad, Mohammad Ebrahim; Fatehpoor, Faranak

    2017-07-01

    Endocrine abnormalities related to polycystic ovary Syndrome (PCOS) are important problems. To compare serum leptin levels between infertile women with and without PCOS. To rank sensitivity of six indirect methods for detection of insulin resistance (IR) and to evaluate the association between leptin and IR in PCOS group. This Case-controlled study performed on 189 infertile women referred to Shiraz Mother and Child Hospital during 2012-2015. Ninety-nine PCOS cases according to Rotterdam criteria were compared to 90 cases without PCOS. Serum leptin, body mass index (BMI), several hormones, and their correlation coefficients with leptin were compared. IR in PCOS women was measured by indirect methods, including fasting blood sugar (FBS), fasting insulin (FI), glucose/insulin, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and MacAuley index. Association between IR and leptin was evaluated. Independent sample t-test and Pearson's test were used. Infertile women with PCOS had higher BMI (26.47±3.62 vs. 24.82±5.18 kg/m 2 ) and serum leptin levels (41.79±187.89 vs. 19.38±12.57 ng/mL). Leptin showed significant association with weight and BMI in both groups (pPCOS group. HOMA-IR showed the highest rate of IR followed by FI and QUICKI methods. The mean leptin levels had positive association with IR assessed by HOMA-IR (pPCOS infertile women. HOMA-IR followed by FI and QUICKI is the most sensitive test for detection of IR.

  12. Higher insulin and higher body fat via leptin are associated with disadvantageous decisions in the Iowa gambling task.

    Science.gov (United States)

    Chang, Douglas C; Piaggi, Paolo; Burkholder, Joushua E; Votruba, Susanne B; Krakoff, Jonathan; Gluck, Marci E

    2016-12-01

    Elevated body mass index and post-prandial state are associated with disadvantageous choices on the Iowa Gambling Task (IGT). Whether physiological factors including percent body fat, and peripheral glucose, insulin, and leptin concentrations, are associated with IGT performance is unknown. In196 healthy adults without diabetes, we measured body fat by DXA scan, glucose, insulin and leptin (n=138) concentrations during an oral glucose tolerance test and IGT performance after a standardized meal. Glucose was not associated with IGT performance. Disadvantageous IGT performance was associated with higher percent body fat (r=-0.16, p=0.03), 30-min insulin concentrations (insulin 30 , r=-0.27, presponsible for the percent body fat effect on IGT performance. Even adjusted for age, sex, race, and education, insulin 30 (b=-46.5, p=0.03) and leptin 30 (b=-50.9, p=0.03) concentrations remained independently associated with IGT performance and interacted together such that higher leptin 30 blunted effects of higher insulin 30 (b=23.8, p=0.048). These findings may indicate an internal metabolic signature of energy availability (higher body fat, insulin, and leptin levels) associated with disadvantageous IGT performance. Published by Elsevier Inc.

  13. [Leptin].

    Science.gov (United States)

    Nedvídková, J

    1997-12-01

    Leptin (ob-protein), a previously unknown protein signal, is secreted from adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks, that regulate weight and energy homeostasis. Leptin provides a communication link between fat tissue and the brain. Ob protein appears to play a major role in the control of body fat stores through coordinated regulation of feeding behavior, metabolism, autonomic nervous system and body energy balance in rodents, primates and humans. Leptin levels have pulsative and diurnal character. In lean subjects with relatively low adipose tissue, the majority of circulating leptin is in the bound form. On other hand, in obese individuals the majority of leptin circulates in free form presumably bioactive protein, and thus obese subjects are resistant to free leptin. Leptin's resistance is often coupled with insuline resistance postreceptor type. Leptin receptor is product of db genes. Ob-protein receptor belongs to the cytokine superfamily of receptors and has several variants. Leptin-receptor gene is expressed in abundant degree in ovary, uterus, testes, less in hypothalamus, hypophysis, and little in kidney. Leptin stimulates the reproductive endocrine system and may serve as a permissive signal to the reproductive system of normal animals. Ob-gene product, leptin is regulated by feedings patterns and hormones, such as insulin and glucocorticoids. There is assumed that neuropeptide Y (NPY) and melanocyte-stimulating hormone (MSH) and its receptor (MCR) are a critical components of the biological response to leptin levels. MCR in contrast to leptin receptors are coupled with G-transduction system.

  14. The Effects of Reduction Mammaplasty on Serum Leptin Levels and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hakan Uzun

    2015-01-01

    Full Text Available Background. The reduction mammaplasty has been a well-executed and known procedure in which considerable amount of fatty tissue is removed from the body. The authors aimed to show the effects of the reduction mammaplasty on serum leptin levels and insulin resistance. Methods. 42 obese female patients who had gigantomastia were operated on. We recorded patients’ demographic and preoperative data, including age, weight, height, and body mass index. Fasting serum leptin, glucose, and insulin levels were noted. Homeostasis model assessment scores were calculated. At the postoperative 8th week, patients were reevaluated in terms of above parameters assessing the presence of any difference. Results. Serum leptin levels were decreased postoperatively and the decrease was statistically significant. We were able to show a decrease in homeostasis model assessment score, which indicated an increase in insulin sensitivity, and this change was statistically significant. A significant correlation between body mass index and leptin change was found postoperatively. Conclusion. Reduction mammaplasty is not solely an aesthetic procedure but it decreases serum leptin levels and increases insulin sensitivity, which may help obese women to reduce their cardiovascular risk.

  15. Insulin and leptin levels in overweight and normal-weight Iranian adolescents: The CASPIAN-III study

    Directory of Open Access Journals (Sweden)

    Ehsan Bahrami

    2014-01-01

    Full Text Available Background: In this study, we aim to compare insulin and leptin levels in adolescents with or without excess weight and in those with or without abdominal obesity. Materials and Methods : This case-control study was conducted among 486 samples. We randomly selected 243 overweight and an equal number of normal-weight adolescents from among participants of the third survey of a national surveillance program entitled "Childhood and Adolescence Surveillance and PreventIon of Adult Non-communicable diseases study." Serum insulin and leptin were compared between two groups and their correlation was determined with other variables. Results: The mean age and body mass index (BMI of participants were 14.10 ± 2.82 years and 22.12 ± 6.49 kg/m 2 , respectively. Leptin and insulin levels were higher in overweight than in normal-weight adolescents (P < 0.05. Leptin level was higher in children with abdominal obesity than in their other counterparts (P < 0.001. Leptin level was correlated with age, fasting blood glucose, BMI, and insulin level. Conclusion: Insulin and leptin levels were higher among overweight and obese children, which may reflect insulin and leptin-resistance. Given the complications of excess weight from early life, prevention and controlling childhood obesity should be considered as a health priority.

  16. [The role of alterations in the brain signaling systems regulated by insulin, IGF-1 and leptin in the transition of impaired glucose tolerance to overt type 2 diabetes mellitus].

    Science.gov (United States)

    Shpakov, A O

    2014-01-01

    One of the crucial factors leading to the development of pre-diabetes and type 2 diabetes mellitus (DM2) are the disturbances in the brain hormonal signaling systems regulated by insulin, insulin-like growth factor-1 (IGF-1) and leptin. The causes of these disturbances are the changes in the redox balance and lipid metabolism leading to lipotoxicity and endoplasmic reticulum stress in neuronal cells, as well as the dysfunctions in neurotransmitter systems of the brain that are functionally associated with insulin, IGF-1 and leptin signaling systems. The identification of molecular disturbances in insulin, IGF-1 and leptin systems of the brain in pre-diabetes and DM2 can be used for early diagnostics of these diseases, and to develop new strategies for preventive treatment of DM2 at the pre-diabetic stage. In the review, the literature data and the results of own investigations concerning the changes in the insulin, IGF-1 and leptin systems of the brain in pre-diabetes and DM2 and their role in the etiology and pathogenesis of DM2 are analyzed, and the approaches to restore the functional activity of these systems are discussed.

  17. The Role of Leptin in Maintaining Plasma Glucose During Starvation.

    Science.gov (United States)

    Perry, Rachel J; Shulman, Gerald I

    2018-03-01

    For 20 years it has been known that concentrations of leptin, a hormone produced by the white adipose tissue (WAT) largely in proportion to body fat, drops precipitously with starvation, particularly in lean humans and animals. The role of leptin to suppress the thyroid and reproductive axes during a prolonged fast has been well defined; however, the impact of leptin on metabolic regulation has been incompletely understood. However emerging evidence suggests that, in starvation, hypoleptinemia increases activity of the hypothalamic-pituitary-adrenal axis, promoting WAT lipolysis, increasing hepatic acetyl-CoA concentrations, and maintaining euglycemia. In addition, leptin may be largely responsible for mediating a shift from a reliance upon glucose metabolism (absorption and glycogenolysis) to fat metabolism (lipolysis increasing gluconeogenesis) which preserves substrates for the brain, heart, and other critical organs. In this way a leptin-mediated glucose-fatty acid cycle appears to maintain glycemia and permit survival in starvation.

  18. Correlation Between Insulin, Leptin and Polycystic Ovary Syndrome ...

    African Journals Online (AJOL)

    Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of fertile age. Insulin can stimulate ovarian androgen production in normal women and in women with PCOS. Leptin levels were reduced among women with PCOS treated with insulin sensitizers. Aim: This study aims to ...

  19. Correlation Between Insulin, Leptin and Polycystic Ovary Syndrome

    African Journals Online (AJOL)

    Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of fertile age. Insulin can stimulate ovarian androgen production in normal women and in women with PCOS. Leptin levels were reduced among women with PCOS treated with insulin sensitizers. Aim: This study aims to ...

  20. Plasma resistin, adiponectin and leptin levels in relation to insulin resistance

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.E.T.

    2010-01-01

    Adipose tissue regulates insulin sensitivity via the circulating adipo cytokines, adiponectin, resistin and leptin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. We examined plasma levels of resistin, adiponectin and leptin in 20 lean subjects with mean body mass index (BMI) of 24, and, 36 nondiabetic obese individuals with mean BMI 34. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 30.4±6.5 vs. 14.4±2.9 mg/l, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P < 0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly reduced in obese compared with lean subjects, P < 0.005 and higher in women, P< 0.001. Adiponectin levels showed significant correlation with HOMA-R and this correlation remained significant after adjustment for gender and BMI. Leptin levels were significantly higher in obese subjects and women and correlated with resistin, but, didn't correlate with HOMA-R. In this small group of patients we demonstrated that insulin resistance correlated most strongly and reciprocally with adiponectin levels. Significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for leptin, the correlation with insulin resistance did not achieve statistical significance

  1. Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation.

    Science.gov (United States)

    Angle, Brittany M; Do, Rylee Phuong; Ponzi, Davide; Stahlhut, Richard W; Drury, Bertram E; Nagel, Susan C; Welshons, Wade V; Besch-Williford, Cynthia L; Palanza, Paola; Parmigiani, Stefano; vom Saal, Frederick S; Taylor, Julia A

    2013-12-01

    Exposure to bisphenol A (BPA) is implicated in many aspects of metabolic disease in humans and experimental animals. We fed pregnant CD-1 mice BPA at doses ranging from 5 to 50,000μg/kg/day, spanning 10-fold below the reference dose to 10-fold above the currently predicted no adverse effect level (NOAEL). At BPA doses below the NOAEL that resulted in average unconjugated BPA between 2 and 200pg/ml in fetal serum (AUC0-24h), we observed significant effects in adult male offspring: an age-related change in food intake, an increase in body weight and liver weight, abdominal adipocyte mass, number and volume, and in serum leptin and insulin, but a decrease in serum adiponectin and in glucose tolerance. For most of these outcomes non-monotonic dose-response relationships were observed; the highest BPA dose did not produce a significant effect for any outcome. A 0.1-μg/kg/day dose of DES resulted in some but not all low-dose BPA outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Impact of risperidone on leptin and insulin in children and adolescents with autistic spectrum disorders.

    Science.gov (United States)

    Srisawasdi, Pornpen; Vanwong, Natchaya; Hongkaew, Yaowaluck; Puangpetch, Apichaya; Vanavanan, Somlak; Intachak, Boontarika; Ngamsamut, Nattawat; Limsila, Penkhae; Sukasem, Chonlaphat; Kroll, Martin H

    2017-08-01

    To evaluate the influence of dose and duration of risperidone treatment on cardiovascular and diabetes risk biomarkers in children and adolescents with autistic spectrum disorders (ASDs). In this cross-sectional analysis, a total of 168 ASDs patients (89% male) treated with a risperidone-based regimen for ≥12months were included. Blood samples were analyzed for glucose and lipid metabolic markers, adiponectin, leptin, prolactin, cortisol and high sensitive C-reactive protein. The mean concentrations of glucose, insulin, prolactin and leptin and HOMA-IR significantly rose with risperidone dosage (all PRisperidone treatment disturbed glucose homeostasis and endocrine regulation (particularly leptin) in children and adolescents with ASDs, in a dose- and duration-dependent manner, being suggestive of leptin and insulin resistance mechanisms. Metabolic adverse effects, especially development of type 2 diabetes mellitus should be closely monitored, particularly in individuals receiving high doses and/or long-term risperidone treatment. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  3. The Relationship among Smoking, Plasma Adiponectin, Leptin, Inflammatory Markers and Insulin Resistance

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.Et.

    2011-01-01

    The study aimed to investigate how smoking influences the relationship between fat mass, soluble tumor necrosis factor-α , (TNFα ) receptors 1 and 2 (sTNFR1 and sTNFR2), highly sensitive C-reactive protein (hs-CRP), adiponectin, leptin and insulin resistance. A total of 60 healthy men (age: 27-53 years, body mass index (BMI): 20-35 kg/m2), 30 of whom were never-smokers and 30 smokers, matched for age, BMI and waist-to-hip ratio were included in this study. Those were subdivided into insulin resistant (IR) and insulin sensitive (IS) subgroups. Measures included circulating soluble fractions of the tumor necrosis factor α (TNFα ) receptors (sTNFR1 and sTNFR2) and their relationship to fat mass, fasting plasma adiponectin, leptin, hs-CRP and insulin sensitivity index. Smokers had significantly lower fat mass, lower fasting glucose, insulin and leptin concentrations than nonsmokers. Despite lower fat mass, insulin and leptin, smokers showed significantly increased circulating sTNFR2 levels (3.7±0.8 vs. 2.9±0.8 ng/ml, P=0.03). Being either a smoker or having insulin resistance was independently associated with lower adiponectin concentrations (P = 0.046 and 0.001, respectively). No difference was detected in average hs- CRP concentrations between smokers and nonsmokers (P = 0.18) and between IR and IS subjects (P = 0.13).Both fat mass and smoking are related to increased activity of the TNFα axis. Plasma adiponectin concentrations are lower in smokers and IR subjects. These two mechanisms could be associated with increased cardiovascular risk in smokers

  4. The Relationship among Smoking, Plasma Adiponectin, Leptin, Inflammatory Markers and Insulin Resistance

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.Et

    2012-01-01

    We aimed to study how smoking influences the relationship between fat mass ,soluble tumor necrosis factor-α, (TNF?) receptors 1 and 2 (sTNFR1 and sTNFR2),highly sensitive C-reactive protein(hs-CRP), adiponectin, leptin and insulin resistance.A total of 60 healthy men (age: 27-53 years, body mass index (BMI): 20-35 kg/m 2 ), 30 of whom were never-smokers and 30 smokers, matched for age, BMI and waist-to-hip ratio were included in this study. Those were subdivided into insulin resistant (IR) and insulin sensitive (IS) subgroups. Measures included circulating soluble fractions of the tumor necrosis factor α (TNF α) receptors (sTNFR1 and sTNFR2) and their relationship to fat mass, fasting plasma adiponectin, leptin, hs- CRP and insulin sensitivity index.Smokers had significantly lower fat mass, lower fasting glucose, insulin and leptin concentrations than nonsmokers. Despite lower fat mass, insulin and leptin, smokers showed significantly increased circulating sTNFR2 levels (3.7±0.8 vs. 2.9 ±0.8 ng/ml, π=0.03). Being either a smoker or having insulin resistance was independently associated with lower adiponectin concentrations (π = 0.046 and 0.001, respectively). No difference was detected in average hs- CRP concentrations between smokers and nonsmokers (π = 0.18) and between IR and IS subjects (π = 0.13).Both fat mass and smoking are related to increased activity of the TNFα axis. Plasma adiponectin concentrations are lower in smokers and IR subjects. These two mechanisms could be associated with increased cardiovascular risk in smokers

  5. Turmeric Supplementation Improves Serum Glucose Indices and Leptin Levels in Patients with Nonalcoholic Fatty Liver Diseases.

    Science.gov (United States)

    Navekar, Roya; Rafraf, Maryam; Ghaffari, Aida; Asghari-Jafarabadi, Mohammad; Khoshbaten, Manouchehr

    2017-01-01

    Insulin and leptin resistance are important risk factors for non-alcoholic fatty liver disease (NAFLD). There is limited evidence regarding the effects of turmeric on NAFLD. The aim of this study was to investigate the effects of turmeric supplementation on glycemic status and serum leptin levels in patients with NAFLD. This double-blind randomized controlled clinical trial was conducted on 46 patients with NAFLD (21males and 25 females) aged 20-60 years old and body mass index (BMI) between 24.9 and 40 kg/m2. The turmeric group (n = 23) was given six turmeric capsules daily for 12 weeks. Each capsule contained 500 mg turmeric powder (6×500 mg). The placebo group (n = 23) was given six placebo capsules daily for the same period. Fasting blood samples, anthropometric measurements, and physical activity levels were collected at the baseline and at the end of the study. Daily dietary intakes also were obtained throughout the study. Data were analyzed by independent t test, paired t test and analysis of covariance. Turmeric consumption decreased serum levels of glucose, insulin, HOMA-IR and leptin (by 1.22, 17.69, 19.48 and 21.33% respectively, p Turmeric supplementation improved glucose indexes and serum leptin levels and may be useful in the control of NAFLD complications.

  6. The Effect of Eight Weeks Resistance Training on Leptin and Insulin Resistance in Obese Female

    Directory of Open Access Journals (Sweden)

    S. Khalili

    2013-04-01

    Full Text Available Introduction & Objective: Leptin , the main peptide secreted by adipose tissue, is considered an alarming factor in the regulation of body fat content . With regard to the physiological effect of exercise as one of the potential regulators of leptin secretion from adipose tissue , this study was performed to examine the effects of resistance exercise on leptin. Materials & Methods: Twenty inactive and obese female students (10 controls and 10 experi-mentals participated in this study. The subjects in the experimental group performed an 8 week resistance training program (chest press, leg press, lat pull down, leg curl, bicep curl, leg extension with 60 - 70 percent of 1RM. ELISA was used to measure leptin. Results: The results of this study showed that 8 weeks of resistance training significantly decreased BMI (31.32 kg/m2 versus 29.73 kg/m2 , P=0.0001, weight body (80.5kg versus 76.25kg, P=0.0001, WHR (0.93 ver-sus0.89, P=0.0001 and body fat percent (27.48 versus 24.85, P=0.0001 in EG. Statistically significant differ-ences were not seen in leptin (P=0.939, insulin (P=0.336, glucose (P=0.264 and insulin resistance (P=0.306 between CG and EG. Conclusion: The results of this study showed that , there was no significant difference in leptin levels and insulin resistance between the control and experimental groups, after 8 weeks of resistance training. (Sci J Hamadan Univ Med Sci 2013; 20 (1:59-65

  7. Fasting and postprandial levels of ghrelin, leptin and insulin in lean, obese and anorexic subjects

    Science.gov (United States)

    Krauss, Hanna; Gibas-Dorna, Magdalena; Kupsz, Justyna; Piątek, Małgorzata; Piątek, Jacek

    2013-01-01

    Introduction Ghrelin, leptin and insulin are involved in neurohormonal regulation of energetic homeostasis. Aim We investigated the correlation between nutritional status and plasma levels of leptin, ghrelin and insulin in lean, obese and anorexic subjects. Material and methods Nineteen obese and 18 anorexic adults were enrolled in the study. Seventeen adults with normal body mass index (BMI) served as controls. Blood samples were taken twice: before breakfast and 2 h after breakfast. Fasting and postprandial ghrelin, leptin and insulin were examined. The following correlations were estimated: between BMI and basal level of tested hormones, between insulin and ghrelin, and between insulin and leptin. The threshold level of significance was p ≤ 0.05 for all calculations. Results Basal insulin level was lowest in anorexic patients and greatest in obese subjects. Fasting plasma ghrelin was lower in obesity and higher in anorexia as compared with the controls. Comparing with controls, fasting leptin levels were higher in obese and lower in anorexic subjects. There was positive correlation between BMI and basal leptin level in obesity. A significant postprandial increase was noted for insulin in all studied groups. Increased leptin and decreased ghrelin levels were detected 2 h after a meal in the control group. In obese patients, postprandial leptin was lower than before food intake, and fasting leptin showed positive correlation with basal insulin level. Conclusions Basal plasma ghrelin, leptin and insulin levels differ according to nutritional status. Impaired ghrelin and leptin secretion and insulin sensitivity may be involved in the pathogenesis of eating disorders. PMID:24868288

  8. Clinical significance of changes of serum leptin and insulin levels in patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Chen Zhaojun; Zhang Lahong; Gao Ying; Ren Xiaohua

    2007-01-01

    Objective: To explore the relationship between the serum leptin, insulin levels and development of polycystic ovary syndrome (PCOS). Methods: Serum leptin and insulin levels (with RIA) were determined in 34 patients with PCOS and 30 controls. Results: The serum leptin and insulin levels in the 34 PCOS patients were significantly higher than those in controls (P<0. 01), and those in obese patients (n=22) were significantly higher than those in non-obese ones (n=12) too(P<0.01). Conclusion: Changes of serum leptin and insulin levels were closely related to the development of PCOS and leptin might be used as a diagnostic indicator for PCOS. (authors)

  9. Correlation of insulin resistance with serum C-reactive protein, adiponectin and leptin levels in patients with type 2 diabetes

    International Nuclear Information System (INIS)

    Duan Yangqiang; Wang Zuobing; Yu Hui

    2012-01-01

    Objective: To explore the relationship between serum C-reactive protein (CRP), adiponectin (APN), leptin (Leptin) levels, insulin resistance index (HOMA-IR) and type 2 diabetes mellitus (T2DM) disease susceptibility. Methods: The plasma leptin and insulin (FINS) levels in the DM patients were determined by RIA, and the serum ANP levels were determined by ELSIA. The CRP, conventional serum fasting plasma glucose (FPG) levels were determine by automatic biochemistry analyzer. The insulin resistance index (HOMA-IR, FPG x FINS/22.5) was calculated. The result was analyzed with normal healthy control group. Results: The serum CRP and leptin, HOMA-IR levels in T2DM group were significantly higher than that of in control group (P< 0.01), and the serum ANP was significantly lower than in control group (P<0.01). The HOMA-IR in T2DM was positively correlated with serum CRP (r= 0.36, P<0.05) and leptin(r= 0.39, P<0.05), and was negatively correlated with serum APN (r=0.32, P<0.05). Conclusion: The high serum CRP and leptin and low APN levels hyperlipidaemia might be factors for diabetes, and their metabolic disorders may be closely related with insulin resistance in patients with type 2 diabetes. (authors)

  10. Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanisms.

    Science.gov (United States)

    Schwartz, M W; Prigeon, R L; Kahn, S E; Nicolson, M; Moore, J; Morawiecki, A; Boyko, E J; Porte, D

    1997-09-01

    Like insulin, the adipocyte hormone, leptin, circulates at levels proportionate to body adiposity. Because insulin may regulate leptin secretion, we sought to determine if plasma leptin levels are coupled to body adiposity via changes in circulating insulin levels or insulin sensitivity and whether leptin secretion from adipocytes is impaired in subjects with NIDDM. We used multiple linear regression to analyze relationships between BMI (a measure of body adiposity) and fasting plasma levels of leptin and insulin in 98 nondiabetic human subjects (68 men/30 women) and 38 subjects with NIDDM (27 men/11 women). The insulin sensitivity index (Si) was also determined in a subset of nondiabetic subjects (n = 38). Fasting plasma leptin concentrations were correlated to both BMI (r = 0.66, P = 0.0001) and fasting plasma insulin levels (r = 0.65, P = 0.0001) in nondiabetic men and women (r = 0.58, P = 0.0009 for BMI; r = 0.47, P = 0.01 for insulin). While the plasma leptin level was also inversely related to Si (r = -0.35; P = 0.03), this association was dependent on BMI, whereas the association between insulin and Si was not. Conversely, the relationship between plasma leptin and BMI was independent of Si, whereas that between insulin and BMI was dependent on Si. The relationship between plasma leptin levels and BMI did not differ significantly among NIDDM subjects from that observed in nondiabetic subjects. We conclude that 1) body adiposity, sex, and the fasting insulin level are independently associated with plasma leptin level; 2) because NIDDM does not influence leptin levels, obesity associated with NIDDM is unlikely to result from impaired leptin secretion; and 3) insulin sensitivity contributes to the association between body adiposity and plasma levels of insulin, but not leptin. The mechanisms underlying the association between body adiposity and circulating levels of these two hormones, therefore, appear to be different.

  11. Comparative Study of Serum Leptin and Insulin Resistance Levels Between Korean Postmenopausal Vegetarian and Non-vegetarian Women.

    Science.gov (United States)

    Kim, Mi-Hyun; Bae, Yun-Jung

    2015-07-01

    The present study was conducted to compare serum leptin and insulin resistance levels between Korean postmenopausal long-term semi-vegetarians and non-vegetarians. Subjects of this study belonged to either a group of postmenopausal vegetarian women (n = 54), who maintained a semi-vegetarian diet for over 20 years or a group of non-vegetarian controls. Anthropometric characteristics, serum leptin, serum glucose, serum insulin, insulin resistance (HOMA-IR; Homeostasis Model Assessment of Insulin Resistance), and nutrient intake were compared between the two groups. The vegetarians showed significantly lower body weight (p vegetarians. The HOMA-IR of the vegetarians was significantly lower than that of the non-vegetarians (p vegetarian diet might be related to lower insulin resistance independent of the % of body fat in postmenopausal women.

  12. Strength and independence of associations between ghrelin, leptin, adiponectin and insulin in stimulating basic functions to energy metabolism

    Directory of Open Access Journals (Sweden)

    Hoda A. Nour

    2014-03-01

    Methods: The present study was conducted on 40 male albino rats that were divided into 4 groups (n = 10: (I: fed ad/libitum, (II: fasted group, refed group allowed for 20 min refeeding with food stuffs divided into two groups, (III: carbohydrate meal, (IV: fat meal. The present study suggests a physiological interaction of ghrelin and leptin in the periphery. Elevated fasting ghrelin appears to modulate other hormonal systems that participate in the regulation of food intake. Ghrelin inhibition after feeding is related to different nutrients satiating capacity. In addition to feeding, several hormonal states have also been involved in the suppression of postprandial ghrelin production. Meal and insulin were found to acutely affect leptin concentration. Inverse change in ghrelin and leptin between fasting and refeeding state may indicate a role of gastric leptin in regulating ghrelin secretion. Positive correlation between adiponectin and insulin with both macronutrients suggests a role of adiponectin in enhancing insulin action. The fact that gastric leptin is stimulated by diet and ghrelin responses could be due to direct effects of multiple hormonal signals which require postgastric feed back on the stomach among the latters (glucose and insulin.

  13. Vitamin C inhibits leptin secretion and some glucose/lipid metabolic pathways in primary rat adipocytes.

    Science.gov (United States)

    Garcia-Diaz, D F; Campion, J; Milagro, F I; Boque, N; Moreno-Aliaga, M J; Martinez, J A

    2010-07-01

    Antioxidant-based treatments are emerging as an interesting approach to possibly counteract obesity fat accumulation complications, since this is accompanied by an increased systemic oxidative stress. The aim of this study was to analyze specific metabolic effects of vitamin C (VC) on epididymal primary rat adipocytes. Cells were isolated and incubated for 72 h in culture medium, in the absence or presence of 1.6 nM insulin, within a range of VC concentrations (5-1000 microM). Glucose- and lipid-related variables as well as the secretion/expression patterns of several obesity-related genes were assessed. It was observed that VC dose dependently inhibited glucose uptake and lactate production, and also reduced glycerol release in both control and insulin-treated cells. Also, VC caused a dramatic concentration-dependent fall in leptin secretion especially in insulin-stimulated cells. In addition, VC (200 microM) induced Cdkn1a and Casp8, partially inhibited Irs3, and together with insulin drastically reduced Gpdh (listed as Gpd1 in the MGI database) gene expressions. Finally, VC and insulin down-regulatory effects were observed on extracellular and intracellular reactive oxygen species production respectively. In summary, this experimental assay describes a specific effect of VC in isolated rat adipocytes on glucose and fat metabolism, and on the secretion/expression of important obesity-related proteins.

  14. Changes of serum leptin and their relationships with insulin resistance in patients with simple obesity and patients with type 2 diabetes mellitus complicated with obesity

    International Nuclear Information System (INIS)

    Zhang Lei; Changzhou Wujin People's Hospital of Jiangsu Province, Changzhou; Shi Linlin; Lu Dan; Zhang Lei; Wang Qing; Yao Wenhua

    2005-01-01

    Objective: To study the changes of serum leptin in patients with simple obesity and patients with type 2 diabetes mellitus complicated with obesity in order to explore the relationship of leptin and insulin resistance and the role of leptin in the occurrence of type 2 diabetes mellitus. Methods: 60 cases of simple obesity, 60 cases of type 2 diabetes mellitus and 30 cases of normal control were included according to the diagnostic criteria of obesity and type 2 diabetes mellitus. the levels of fasting serum leptin, fasting serum insulin, fasting glucose, fasting blood lipid were measured in all cases. The body mass index (BMI) and insulin action index were calculated. Results: The level of BMI, serum leptin, serum insulin, blood lipid were significantly higher in patients with simple obesity and with type 2 diabetes mellitus complicated with obesity than in normal control cases, while (IAI) was significantly lower. The levels of free serum leptin, serum insulin, free glucose, and blood lipid were significantly higher in patients with type 2 diabetes mellitus complicated with obesity than in patients with simple obesity, while IAI was significantly lower. The level of serum leptin was positively correlated with BMI (r=0.48, P<0.55) and fasting serum leptin (r=0.55, P<0.05) and negatively correlated with IAI (r=-0.47, P<0.05) in patients with type 2 diabetes complicated with obesity. Conclusion: The overexpression of serum leptin may play an important role in the occurrence of the insulin resistance and type 2 diabetes mellitus in obesity patients. (authors)

  15. Leptin reverses hyperglycemia and hyperphagia in insulin deficient diabetic rats by pituitary-independent central nervous system actions.

    Directory of Open Access Journals (Sweden)

    Alexandre A da Silva

    Full Text Available The hypothalamic-pituitary-adrenal (HPA axis has been postulated to play a major role in mediating the antidiabetic effects of leptin. We tested if the pituitary is essential for the chronic central nervous system mediated actions of leptin on metabolic and cardiovascular function in insulin-dependent diabetic and non-diabetic rats. Male 12-week-old hypophysectomized Sprague-Dawley rats (Hypo, n = 5 were instrumented with telemetry probes for determination of mean arterial pressure (MAP and heart rate (HR 24-hrs/day and an intracerebroventricular (ICV cannula was placed into the brain lateral ventricle for continuous leptin infusion. In additional groups of Hypo and control rats (n = 5/group, diabetes was induced by single injection of streptozotocin (50 mg/kg, IP. Hypo rats were lighter, had lower MAP and HR (83±4 and 317±2 vs 105±4 mmHg and 339±4 bpm, with similar caloric intake per kilogram of body weight and fasting plasma glucose levels (84±4 vs 80±4 mg/dl compared to controls. Chronic ICV leptin infusion (7 days, 0.62 μg/hr in non-diabetic rats reduced caloric intake and body weight (-10% in Hypo and control rats and markedly increased HR in control rats (~25 bpm while causing only modest HR increases in Hypo rats (8 bpm. In diabetic Hypo and control rats, leptin infusion reduced caloric intake, body weight and glucose levels (323±74 to 99±20 and 374±27 to 108±10 mg/dl, respectively; however, the effects of leptin on HR were abolished in Hypo rats. These results indicate that hypophysectomy attenuates leptin's effect on HR regulation without altering leptin's ability to suppress appetite or normalize glucose levels in diabetes.

  16. Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity.

    Science.gov (United States)

    Vettor, R; De Pergola, G; Pagano, C; Englaro, P; Laudadio, E; Giorgino, F; Blum, W F; Giorgino, R; Federspil, G

    1997-12-01

    Testosterone levels are decreased in obese men but increased in obese women. The interplay between gonadal steroids and leptin is, at present, far from being elucidated. This study was carried out to investigate the relationship between serum leptin, plasma insulin, insulin sensitivity and free testosterone in 46 men (29 obese and 17 lean) and 65 premenopausal women (42 obese and 23 lean). In all subjects, anthropometric parameters and serum levels of insulin, leptin, free testosterone (T), dehydroepiandrosterone sulphate and sex hormone-binding globulin were measured. An oral glucose tolerance test (OGTT) and an insulin tolerance test were also performed to determine the insulin sensitivity index. Our results show a significant difference in serum leptin between lean and obese men (3.19 +/- 0.71 vs. 20.28 +/- 0.26 ng mL-1; P < 0.0005) as well as between lean and obese women (10.78 +/- 2.14 vs. 34.79 +/- 2.26 ng mL-1; P < 0.00001). Basal T concentration in the obese men was significantly lower than in the control group (18.6 +/- 1.3 vs. 23.3 +/- 1.4 ng L-1; P < 0.01), whereas in the obese women it was significantly higher than in the control group (2.0 +/- 0.2 vs. 1.3 +/- 0.1 ng L-1; P < 0.05). When multiple linear regression was performed without body mass index (BMI) in the statistical model, leptin was correlated with basal insulin (P < 0.0001), insulin sensitivity (P < 0.0001) and T (P < 0.0001) in both men and women. When BMI was included in the model as an independent variable, leptin was significantly correlated only with BMI (P < 0.0001), the degree of insulin resistance (P < 0.05) and T (only in men, P < 0.05). This study confirms that serum leptin is strongly correlated with the degree of obesity and female sex. The negative correlation between leptin and T in men, independent of BMI, is consistent with the hypothesis that T may possess an inhibitory effect on adipocyte ob gene transcription.

  17. Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis

    DEFF Research Database (Denmark)

    Perry, Rachel J; Petersen, Kitt Falk; Shulman, Gerald I.

    2016-01-01

    In this review we discuss the mechanisms for the pleotropic effects of leptin replacement therapy to reverse liver and muscle insulin resistance in lipodystrophic individuals, as well as insulin-independent effects of leptin replacement therapy to suppress white adipose tissue lipolysis, hepatic ...

  18. Obese Neuronal PPARγ Knockout Mice Are Leptin Sensitive but Show Impaired Glucose Tolerance and Fertility.

    Science.gov (United States)

    Fernandez, Marina O; Sharma, Shweta; Kim, Sun; Rickert, Emily; Hsueh, Katherine; Hwang, Vicky; Olefsky, Jerrold M; Webster, Nicholas J G

    2017-01-01

    The peroxisome-proliferator activated receptor γ (PPARγ) is expressed in the hypothalamus in areas involved in energy homeostasis and glucose metabolism. In this study, we created a deletion of PPARγ brain-knockout (BKO) in mature neurons in female mice to investigate its involvement in metabolism and reproduction. We observed that there was no difference in age at puberty onset between female BKOs and littermate controls, but the BKOs gave smaller litters when mated and fewer oocytes when ovulated. The female BKO mice had regular cycles but showed an increase in the number of cycles with prolonged estrus. The mice also had increased luteinizing hormone (LH) levels during the LH surge and histological examination showed hemorrhagic corpora lutea. The mice were challenged with a 60% high-fat diet (HFD). Metabolically, the female BKO mice showed normal body weight, glucose and insulin tolerance, and leptin levels but were protected from obesity-induced leptin resistance. The neuronal knockout also prevented the reduction in estrous cycles due to the HFD. Examination of ovarian histology showed a decrease in the number of primary and secondary follicles in both genotypes due to the HFD, but the BKO ovaries showed an increase in the number of hemorrhagic follicles. In summary, our results show that neuronal PPARγ is required for optimal female fertility but is also involved in the adverse effects of diet-induced obesity by creating leptin resistance potentially through induction of the repressor Socs3. Copyright © 2017 by the Endocrine Society.

  19. Dietary fat and insulin resistance: a connection through leptin and PPARγ activation

    Directory of Open Access Journals (Sweden)

    Doaa Nader Al-Jada

    2016-06-01

    Full Text Available Insulin resistance refers to reduced insulin action in peripheral tissues and impaired suppression of endogenous glucose production, a state which is critical for maintaining normal glucose homeostasis. Insulin resistance is partly explained by genetic factors and is strongly influenced by the individual's habitual lifestyle. Investigating factors that may influence the development of insulin resistance and their mechanisms of action is highly significant; one of these factors include dietary fat. Both quantitative and qualitative terms of dietary fat have been known to play an important role in the development of insulin resistance, although the mechanism underlying this effect is not fully understood. In this regard, the classical view has been that dietary fat quality mainly affects cell membrane fatty acid composition and consequently the membrane function. Recently, the relationship between dietary fat and insulin resistance has entered an advanced level due to the discovery that different fatty acids can regulate gene expression, transcriptional activity and adipocytokines secretion. In essence, this provides new mechanisms by which fatty acids exert their cellular effects. The present review critically assesses the effect of dietary fat quality on the development of insulin resistance in relation to the adipocytokine, leptin and the activation of the transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ. It is evident that fat quality influences the development of insulin resistance and has a more important role than quantity. Leptin and PPARγ prove to be potential candidates linking dietary fat with insulin resistance. However, the exact role or mechanism of action of various types of dietary fat in the development of insulin resistance is still uncertain. Further well-controlled studies in humans are necessary to establish better evidence-based dietary fat recommendations for diabetes prevention and its

  20. Central infusion of ketone bodies modulates body weight and hepatic insulin sensitivity by modifying hypothalamic leptin and insulin signaling pathways in type 2 diabetic rats.

    Science.gov (United States)

    Park, Sunmin; Kim, Da Sol; Daily, James W

    2011-07-15

    Although the effects of ketogenic diets on energy and glucose homeostasis have been controversial, elevation of serum ketone levels by subcutaneous injection of β-hydroxybutyrate (BHB) can improve glucose homeostasis. Ketones may work through the brain; therefore, we evaluated whether the intracerebroventricular (ICV) infusion of β-hydroxybutyrates would also modulate peripheral energy and glucose homeostasis, and through what mechanisms, in diabetic rats fed a high fat diet in short- and long-term studies. Short-term (3h) central injection of BHB (50 μg/h) improved serum glucose levels and peripheral insulin sensitivity compared to the artificial cerebrospinal fluid (CSF) group among 90% pancreatectomized (Px) diabetic rats, but not in non-diabetic Sham rats. In addition to short-term infusion, long-term (28 days) central infusion of BHB (12 μg/h) elevated serum BHB levels. Long-term infusion of BHB potentiated leptin and insulin signaling in the hypothalamus to slightly decrease body weight in Px rats. Central BHB infusion had a greater effect on peripheral glucose metabolism than overall energy metabolism. Hepatic insulin signaling (tyrosine phosphorylation of IRS2→serine phosphorylation of Akt→reduced expression of PEPCK) was potentiated and hepatic glucose production in the hyperinsulinemic state was suppressed in the diabetic rats. In addition, glucose tolerance was improved by central BHB infusion through enhanced whole body glucose disposal rates, but insulin secretion was not affected in the diabetic rats. In conclusion, mild ketosis by central infusion of ketones improves energy and glucose metabolism through the potentiation of leptin and insulin signaling in the hypothalamus of diabetic rats. Copyright © 2011. Published by Elsevier B.V.

  1. Insulin downregulates the expression of the Ca2+-activated nonselective cation channel TRPM5 in pancreatic islets from leptin-deficient mouse models.

    Science.gov (United States)

    Colsoul, Barbara; Jacobs, Griet; Philippaert, Koenraad; Owsianik, Grzegorz; Segal, Andrei; Nilius, Bernd; Voets, Thomas; Schuit, Frans; Vennekens, Rudi

    2014-03-01

    We recently proposed that the transient receptor potential melastatin 5 (TRPM5) cation channel contributes to glucose-induced electrical activity of the β cell and positively influences glucose-induced insulin release and glucose homeostasis. In this study, we investigated Trpm5 expression and function in pancreatic islets from mouse models of type II diabetes. Gene expression analysis revealed a strong reduction of Trpm5 mRNA levels in pancreatic islets of db/db and ob/ob mice. The glucose-induced Ca(2+) oscillation pattern in db/db and ob/ob islets mimicked those of Trpm5 (-/-) islets. Leptin treatment of ob/ob mice not only reversed the diabetic phenotype seen in these mice but also upregulated Trpm5 expression. Leptin treatment had no additional effect on Trpm5 expression levels when plasma insulin levels were comparable to those of the vehicle-injected control group. In murine β cell line, MIN6, insulin downregulated TRPM5 expression in a dose-dependent manner, unlike glucose or leptin. In conclusion, our data show that increased plasma insulin levels downregulate TRPM5 expression in pancreatic islets from leptin-deficient mouse models of type 2 diabetes.

  2. CORRELATION BETWEEN GUT MICROBIOTA AND DEVELOPMENT OF GLUCOSE INTOLERANCE IN B6.V-Lepob/J LEPTIN DEFICIENT MICE

    DEFF Research Database (Denmark)

    Ellekilde, Merete; Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris

    -Lepob/J leptin deficient mouse, a model of severe obesity and type 2 diabetes, was correlated with development of glucose intolerance. GM composition was analyzed by means of denaturing gradient gel electrophoresis (DGGE), a culture independent approach, separating PCR-derived DNA amplicons of bacterial 16S r......RNA. Disease development was monitored by weekly weight and blood glucose measurements supplemented with measurements of oral glucose tolerance, HbA1c%, plasma insulin and plasma cytokines. A significant correlation was demonstrated between GM composition and glucose intolerance. Also, a significant...... correlation was found between blood glucose, HbA1c% and glucose intolerance and the pro-inflammatory cytokine IL-12, supporting the correlation found between gut and disease, as IL-12 is secreted after microbial stimulation of immunological cells – e.g. In the gut. Further investigations concerning...

  3. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study.

    OpenAIRE

    Zimmet, P.; Hodge, A.; Nicolson, M.; Staten, M.; de Courten, M.; Moore, J.; Morawiecki, A.; Lubina, J.; Collier, G.; Alberti, G.; Dowse, G.

    1996-01-01

    OBJECTIVE: To measure serum leptin concentrations in the Polynesian population of Western Samoa and to examine epidemiological associations of leptin with anthropometric, demographic, behavioural, and metabolic factors in this population with a high prevalence of obesity and non-insulin dependent diabetes mellitus. DESIGN: Cross sectional study, leptin concentration being measured in a subgroup of a population based sample. SUBJECTS: 240 Polynesian men and women aged 28-74 years were selected...

  4. Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study. The Hoorn Study

    NARCIS (Netherlands)

    Ruige, J B; Dekker, J M; Blum, W F; Stehouwer, C D; Nijpels, G; Mooy, J; Kostense, P J; Bouter, L M; Heine, R J

    OBJECTIVE: Leptin is thought to play a key role in the control of body weight. There is a complex interrelationship between leptin and insulin or insulin resistance, but it is unknown how leptin is regulated. We therefore explored, in a large population-based study of 2,484 Caucasian subjects aged

  5. Comparison of the effects of endurance, resistance and concurrent training on insulin resistance and adiponectin-leptin ratio in diabetic rat

    Directory of Open Access Journals (Sweden)

    A. Saremi

    2017-08-01

    Full Text Available Background: The obesity-related hormones leptin and adiponectin are independently and oppositely associated with insulin resistance. Objective: The aim of the present study was to investigate the effect of endurance, resistance and concurrent training on insulin resistance and adiponectin-leptin ratio in diabetic rats. Methods: Ten out of 50 male Wistar rats were separated as healthy subjects. Then diabetes was induced in the remaining rats by the injection of streptozotocin. Diabetic rats divided into 4 groups: Control, resistance training (5 sessions/week, 4 reps/3 sets, endurance training (5 sets per week of treadmill running and concurrent training. The resistance training protocol consisted of ten weeks climbing up the ladder, while endurance training performed on treadmill for ten weeks. Concurrent training group completed a combination of both resistances and endurance treadmill training. Blood samples were taken to assess leptin, adiponectin and insulin resistance. Findings: Endurance, resistance and concurrent training significantly decreased insulin resistance and glucose (P0.05. On the one hand, adiponctin level and adiponctin-leptin ratio significantly increased in all of training groups (P<0.05. Conclusion: Exercise training, as defined in this study, leads to improvements in adiponectin-leptin ratio and concurrent training has more impact on insulin resistance index in diabetic rats.

  6. Leptin responses to bovine interferon- α and insulin in cattle

    African Journals Online (AJOL)

    Leptin is a protein synthesized and secreted mainly by adipose tissue. Peripheral administration of different inflammatory cytokines increases both leptin protein and mRNA expression in rodents. We previously showed that injection of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-α) did not affect leptin ...

  7. Plasma levels of leptin, omentin, collagenous repeat-containing sequence of 26-kDa protein (CORS-26 and adiponectin before and after oral glucose uptake in slim adults

    Directory of Open Access Journals (Sweden)

    Schäffler Andreas

    2007-02-01

    Full Text Available Abstract Background Adipose tissue secreted proteins are collectively named adipocytokines and include leptin, adiponectin, resistin, collagenous repeat-containing sequence of 26-kDa protein (CORS-26 and omentin. Several of these adipocytokines influence insulin sensitivity and glucose metabolism and therefore systemic levels may be affected by oral glucose uptake. Whereas contradictory results have been published for leptin and adiponectin, resistin has not been extensively investigated and no reports on omentin and CORS-26 do exist. Methods Therefore the plasma levels of these proteins before and 120 min after an oral glucose load were analyzed in 20 highly-insulin sensitive, young adults by ELISA or immunoblot. Results Circulating leptin was reduced 2 h after glucose uptake whereas adiponectin and resistin levels are not changed. Distribution of adiponectin and CORS-26 isoforms were similar before and after glucose ingestion. Omentin is highly abundant in plasma and immunoblot analysis revealed no alterations when plasma levels before and 2 h after glucose intake were compared. Conclusion Taken together our data indicate that only leptin is reduced by glucose uptake in insulin-sensitive probands whereas adiponectin and resistin are not altered. CORS-26 was demonstrated for the first time to circulate as high molecular weight form in plasma and like omentin was not influenced by oral glucose load. Omentin was shown to enhance insulin-stimulated glucose uptake but systemic levels are not correlated to postprandial blood glucose.

  8. Changes of serum leptin, adiponection and insulin levels in females with simple obesity

    International Nuclear Information System (INIS)

    Wei Tao; Duan Wennuo; Ma Yongxiu; Chen Yanping

    2004-01-01

    Objective: To study the changes of serum leptin, insulin and adiponectin levels and their relationship with BMI in females with simple obesity. Methods: Serum leptin, adiponectin and insulin levels were measured with RIA in 48 pre-obese females (BMI=23-24.9 kg/m 2 ), 40 females with simple obesity, (BMI≥25 kg/m 2 ) and 42 female controls (BMI 18-22.9 kg/m 2 ). Correlations among these variables were studied. Results: Serum leptin, insulin levels were significantly higher and serum adiponectin levels were significantly lower in both the pre-obese and obese females than those in controls. Serum leptin, insulin levels were positively correlated to BMI; Serum adiponectin levels were negatively correlated to BMI. Conclusion: Within normal range of BMI, the leptin-insulin feedback mechanism provided satisfactory self-regulation. However, with excessive BMI, this dynamic equilibrium would be disrupted. The defective equilibrium, together with the abnormal low adiponectin level, would predispose to the development of diabetes mellitus. (authors)

  9. Living without insulin: the role of leptin signaling in the hypothalamus

    OpenAIRE

    Fujikawa Teppei; Coppari Roberto

    2015-01-01

    Since its discovery in 1922, insulin has been thought to be required for normal metabolic homeostasis and survival. However, this view would need to be revised as recent results from different laboratories have convincingly indicated that life without insulin is possible in rodent models. These data indicate that particular neuronal circuitries, which include hypothalamic leptin-responsive neurons, are empowered with the capability of permitting life in complete absence of insulin. Here, we r...

  10. Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

    Directory of Open Access Journals (Sweden)

    Maristella A. Landgraf

    2014-03-01

    Full Text Available Background/Aims: We investigated the effects of leptin in the development of lipopolysaccharide (LPS-induced acute lung inflammation (ALI in lean mice. Methods: Mice were administered leptin (1.0µg/g or leptin (1.0µg/g followed by LPS (1.5µg/g intranasally. Additionally, some animals were given LPS (1.5µg/g or saline intranasally alone, as a control. Tissue samples and fluids were collected six hours after instillation. Results: We demonstrated that leptin alone did not induce any injury. Local LPS exposure resulted in significant acute lung inflammation, characterized by a substantial increase in total cells, mainly neutrophils, in bronchoalveolar lavages (BAL. We also observed a significant lymphocyte influx into the lungs associated with enhanced lung expression of chemokines and cytokines (KC, RANTES, TNF-α, IFN-γ, GM-CSF and VEGF. LPS-induced ALI was characterized by the enhanced expression of ICAM-1 and iNOS in the lungs. Mice that received LPS showed an increase in insulin levels. Leptin, when administered prior to LPS instillation, abolished all of these effects. LPS induced an increase in corticosterone levels, and leptin potentiated this event. Conclusion: These data suggest that exogenous leptin may promote protection during sepsis, and downregulation of the insulin levels and upregulation of corticosterone may be important mechanisms in the amelioration of LPS-induced ALI.

  11. Relationships between changes in leptin and insulin resistance levels in obese individuals following weight loss

    Directory of Open Access Journals (Sweden)

    Tsu-Nai Wang

    2013-08-01

    Full Text Available Obesity can augment insulin resistance (IR, leading to increased risk of diabetes and heart disease. Leptin, ghrelin, and various fatty acids present in the cell membrane may modulate IR. In this study, we aimed to investigate the impact of weight loss on IR, serum leptin/ghrelin levels, and erythrocyte fatty acids, and studied the associations between changes in these variables. A total of 35 obese (body mass index ≥ 27 adults participated in a weight loss program for 3 months. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR. The obese participants had a mean weight loss of 5.6 ± 3.8 kg followed by a 16.7% and 23.3% reduction in HOMA-IR and leptin (p  0.05 levels. After adjusting for age, gender, changes in ghrelin, and body fat, we found a significant correlation between decreases in leptin and less risk of no improvement in HOMA-IR levels [odds ratio (OR = 0.69, p = 0.039]. In conclusion, a moderate weight reduction in obese participants over a short period significantly improved IR. This weight reduction concomitantly decreased serum leptin, increased ghrelin, and elevated some erythrocyte unsaturates. Only leptin correlated independently with IR improvement upon multivariable logistic regression analysis, which indicates that leptin may play a role in the modulation of IR following weight loss.

  12. Common genetic variation in the SERPINF1 locus determines overall adiposity, obesity-related insulin resistance, and circulating leptin levels.

    Directory of Open Access Journals (Sweden)

    Anja Böhm

    Full Text Available OBJECTIVE: Pigment epithelium-derived factor (PEDF belongs to the serpin family of peptidase inhibitors (serpin F1 and is among the most abundant glycoproteins secreted by adipocytes. In vitro and mouse in vivo data revealed PEDF as a candidate mediator of obesity-induced insulin resistance. Therefore, we assessed whether common genetic variation within the SERPINF1 locus contributes to adipose tissue-related prediabetic phenotypes in humans. SUBJECTS/METHODS: A population of 1,974 White European individuals at increased risk for type 2 diabetes was characterized by an oral glucose tolerance test with glucose and insulin measurements (1,409 leptin measurements and genotyped for five tagging SNPs covering 100% of common genetic variation (minor allele frequency ≥ 0.05 in the SERPINF1 locus. In addition, a subgroup of 486 subjects underwent a hyperinsulinaemic-euglycaemic clamp and a subgroup of 340 magnetic resonance imaging (MRI and spectroscopy (MRS. RESULTS: After adjustment for gender and age and Bonferroni correction for the number of SNPs tested, SNP rs12603825 revealed significant association with MRI-derived total adipose tissue mass (p = 0.0094 and fasting leptin concentrations (p = 0.0035 as well as nominal associations with bioelectrical impedance-derived percentage of body fat (p = 0.0182 and clamp-derived insulin sensitivity (p = 0.0251. The association with insulin sensitivity was completely abolished by additional adjustment for body fat (p = 0.8. Moreover, the fat mass-increasing allele of SNP rs12603825 was significantly associated with elevated fasting PEDF concentrations (p = 0.0436, and the PEDF levels were robustly and positively associated with all body fat parameters measured and with fasting leptin concentrations (p<0.0001, all. CONCLUSION: In humans at increased risk for type 2 diabetes, a functional common genetic variant in the gene locus encoding PEDF contributes to overall body adiposity

  13. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability

    NARCIS (Netherlands)

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W.; Pfluger, Paul T.; Fernandez, Ana M.; Luquet, Serge; Woods, Stephen C.; Torres-Alemán, Ignacio; Kahn, C. Ronald; Götz, Magdalena; Horvath, Tamas L.; Tschöp, Matthias H.

    2016-01-01

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and

  14. Coffee Consumption Attenuates Insulin Resistance and Glucose ...

    African Journals Online (AJOL)

    Coffee Consumption Attenuates Insulin Resistance and Glucose Intolerance in Rats fed on High-Sucrose Diet. ... Summary: Several epidemiological evidences indicate that consumption of coffee is associated with a lower risk of type 2 diabetes mellitus (T2DM) however; there is dearth of experimental data to support these ...

  15. Glucose control: Non-insulin therapies

    African Journals Online (AJOL)

    Volume 56 No 1. S Afr Fam Pract 2014. Glucose control: Non-insulin therapies. This article is a direct extraction from Chapter 9 of The 2012 SEMDSA Guidelines for the Management of Type 2 Diabetes and should be read in conjunction with the SEMDSA 2012 Treatment Algorithm. The full guideline and poster summary is ...

  16. Coffee Consumption Attenuates Insulin Resistance and Glucose ...

    African Journals Online (AJOL)

    olayemitoyin

    J. Physiol. Sci. 28(December 2013) 179–185 www.njps.com.ng. Coffee Consumption Attenuates Insulin Resistance and Glucose. Intolerance in Rats fed on High-Sucrose Diet. Morakinyo AO*, Adekunbi DA, Dada KA and Adegoke OA. Department of Physiology, College of Medicine of the University of Lagos, Lagos. Nigeria.

  17. Blood glucose lowering effect of ophiopogonis tuber extract and mechanism of anti-insulin-resistance

    Directory of Open Access Journals (Sweden)

    Meng NING

    2013-01-01

    Full Text Available Objective  To study the hypoglycemic effect and insulin sensitization mechanism of ophiopogonis tuber extracts on the 3T3-L1-induced adipocytes, and also in rats with reproduction of type 2 diabetes mellitus (T2DM. Methods  3T3-L1 cells were induced and differentiated into adipocytes. After the intervention with ophiopogonpolysaccharide (OPSR and ophiopogonin (OPG, glucose consuming rate was detected for screening the extracts which may have effective hypoglycemic effects. The insulin resistance (IR adipocyte model was established by dexamethasone induction, and then it was treated with OPSR. The protein expression levels of leptin, adiponectin and resistin were detected by Western blotting. The T2DM rat model was reproduced and then treated with OPSR for 4 weeks. Body weight (BW, triglyeride (TG, fasting blood glucose (FBG and fasting insulin (FINs of the rats were measured respectively. Results  OPSR in dosage of 0.5-50mg/L promoted glucose consumption of adipocytes in a dose-dependent manner, the glucose consumption ratios were 32.27%, 75.14% and 90.47% respectively. OPG of 50mg/L showed very weak activity with glucose consumption ratio of only 8.49%. OPSR could significantly promote the protein expression of leptin and adiponectin, and showed an inhibitory effect on the protein expression of resistin (P<0.05. After treatment with OPSR for 4 weeks, the BW of rats increased obviously, while TG, FBG and HOMA-IR decreased significantly (P<0.05 or P<0.01. Conclusions  OPSR may promote glucose transport and utilization of adipocytes, decrease the level of FBG and TG, and improve the condition of IR in T2DM rats. The mechanism of blood glucose lowering effect may be attributed to secretion of adipokines, such as leptin, adiponectin and resistin by IR adipocytes.

  18. Relation of Absolute or Relative Adiposity to Insulin Resistance, Retinol Binding Protein-4, Leptin, and Adiponectin in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    You Lim Kim

    2012-12-01

    Full Text Available BackgroundCentral fat mass (CFM correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications; however, peripheral fat mass (PFM is associated with insulin sensitivity. The aim of this study was to investigate the relation of absolute and relative regional adiposity to insulin resistance index and adipokines in type 2 diabetes.MethodsTotal of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma glucose disappearance (KITT and serum adipokines, such as retinol binding protein-4 (RBP4, leptin, and adiponectin, were measured. Using dual X-ray absorptiometry, trunk fat mass (in kilograms was defined as CFM, sum of fat mass on the lower extremities (in kilograms as PFM, and sum of CFM and PFM as total fat mass (TFM. PFM/TFM ratio, CFM/TFM ratio, and PFM/CFM ratio were defined as relative adiposity.ResultsMedian age was 55.9 years, mean body mass index 27.2 kg/m2, and mean HbA1c level 7.12±0.84%. KITT was positively associated with PMF/TFM ratio, PMF/CFM ratio, and negatively with CFM/TFM ratio, but was not associated with TFM, PFM, or CFM. RBP4 levels also had a significant relationship with PMF/TFM ratio and PMF/CFM ratio. Adiponectin, leptin, and apolipoprotein A levels were related to absolute adiposity, while only adiponectin to relative adiposity. In correlation analysis, KITT in type 2 diabetes was positively related with HbA1c, fasting glucose, RBP4, and free fatty acid.ConclusionThese results suggest that increased relative amount of peripheral fat mass may aggravate insulin resistance in type 2 diabetes.

  19. Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

  20. The roles of the insulin-like growth factor system and leptin as ...

    African Journals Online (AJOL)

    The roles of the insulin-like growth factor system and leptin as possible mediators of the effects of nutritional restriction on age at puberty and compensatory growth in ... and IGFBP-3 are affected by nutritional restriction and repletion, and may contribute in some measure to the endocrine regulation of compensatory growth.

  1. Leptin, insulin like growth factor-1 and thyroid profile in a studied ...

    African Journals Online (AJOL)

    Howida Hosny El Gebali

    2014-02-26

    Feb 26, 2014 ... Leptin, insulin like growth factor-1 and thyroid profile in a studied sample of Egyptian children with Down syndrome. Howida Hosny El Gebali a. , Eman Ahmed ... Subjects and methods: A prospective case control study was conducted on 80 children, classified ...... syndrome and Prader–Willi syndrome.

  2. Leptin, insulin like growth factor-1 and thyroid profile in a studied ...

    African Journals Online (AJOL)

    Background: Several mechanisms have been suggested for obesity in Down syndrome. Aim of the study: Assessment of serum levels of leptin, insulin like growth factor-I (IGF-I), thyroid stimulating hormone (TSH) and free thyroxin (FT4) in a prepubertal Egyptian sample of children with DS compared to their age and sex ...

  3. Serum bile acids and leptin interact with glucose metabolism in patients with liver cirrhosis

    NARCIS (Netherlands)

    Valentini, Luzia; Glaeser, Silja; Schuetz, Tatjana; Omar, Ajmal; Kasim, Esmatollah; Kroencke, Thomas; Tietge, Uwe J. F.; Lochs, Herbert; Schulzke, Joerg-Dieter; Brabant, Georg; Ockenga, Johann

    Background & aims: We investigated possible involvements of bile acids (BA) and leptin in hepatogenous insulin resistance being present in up to 90% of cirrhotic patients. Methods: Blood was analysed in 10 cirrhotic patients (8m/2f, 48 +/- 10.4 yrs) and 10 controls (8m/2f, 43 +/- 9.3 yrs) after oral

  4. The Glucose-Insulin Control System

    DEFF Research Database (Denmark)

    Hallgreen, Christine Erikstrup; Korsgaard, Thomas Vagn; Hansen, RenéNormann N.

    2008-01-01

    are divided into smaller pieces and analyzed via several small biosimulation models that describe events in beta cells, liver, muscle and adipose tissue etc. In the glucose-sensing part, the beta cell are shown to have some characteristics of a classic PID controller, but with nonlinear properties....... Furthermore, the body has also glucose sensors in the intestine, the brain, the portal vein, and to some extent the liver, and they sense very different glucose concentrations. All sensors are incorporated in a dynamic network that is interconnected by both hormones and the nervous system. Regarding glucose...... is influenced by insulin. Another facet is that the control system has to cope with the complex traffic of metabolites inside cells and between organs on time-scales from minutes to months or more. The analysis is evaluated using setups called "virtual experiments", i.e. biosimulation models describing common...

  5. Leptin, visfatin, insulin resistance, and body composition change in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Eker, Suzan; Ayaz, Lokman; Tamer, Lulufer; Ulubas, Bahar

    2010-02-01

    The aim of the study was to compare endocrine parameters such as leptin, visfatin, insulin resistance, exercise capacity and body composition change, the pulmonary functions test (PFT) and arterial blood gases (ABG) parameters of chronic obstructive pulmonary disease (COPD) patients and in healthy controls. Fifty-five patients with COPD and without malnutrition and 25 healthy controls were included in our study. The serum leptin, visfatin, tumor necrosis factor alpha (TNF-alpha) and insulin resistance, body fat-free mass (FFM) and fat mass (FM) were measured in the groups. Additionally, body mass index (BMI) was calculated and the 6-minute walk test (6MWT), PFT and ABG analyses were performed in all of the cases. No difference in BMI between the COPD group and controls was determined. Serum leptin and visfatin levels, FFM and 6MWT distance were significantly lower in the patients with COPD (p leptin levels and BMI (r = 0.333, p = 0.027), and with FM (r = 0.365, p = 0.029). Serum visfatin level was correlated with the percentage of forced expiratory volume in the first second in the patients with COPD (r = 0.371, p = 0.013). HOMA-IR (Homeostasis model assessment of insulin resistance) and serum TNF-alpha levels in the patients with COPD were found to be significantly higher than controls (p = 0.001, p COPD. Evaluating the patients not only with the pulmonary function and also systemically, contributes to minimizing the mortality and morbidity.

  6. Relationship and significance of serum leptin with blood insulin and lipid in 6-13 years old obese children

    International Nuclear Information System (INIS)

    Sheng Chunyong; Wang Chunlan; Zhang Linong

    2005-01-01

    To explore relationship and significance of Serum Leptin with BMI, Insulin, triglyceride (TG) and total cholesterol (TC) in obese children aged 6-13 years. Serum Leptin of school-age children 118 (64 male, 54 female; normal non-obese 56 and obese 62) were deter- mined and compared with BMI, Insulin, TG and TC. The results showed that: (1) Each index of obese children was remarkably higher than that of non-obese children (P 0.05). (3) Leptin was poritinely corelation with BMI, insulin, TG and TC(P=0.001). Leptin level in serum may varied according to sex, BMI or blood lipid level. It is of great significance in prevention and treatment of obesity to use drug which may improve Leptin receptor effect. (authors)

  7. [The investigation of the relationship between Leptin-insulin resistance and pulmonary function in patients with chronic obstructive pulmonary disease with acute exacerbation].

    Science.gov (United States)

    Pan, Hai-Yan; Lu, Xiao-Zhuo; Wang, De-Xi; Zeng, Yu; Zhong, Hai-Bo

    2007-09-01

    To investigate the relationship between Leptin-insulin resistance and pulmonary function in patients with chronic obstructive pulmonary disease (COPD) with acute exacerbation. Fifty-six patients with COPD with acute exacerbation were divided into two groups according to the fasting plasma glucose level [the hyperglycemia group: fasting blood glucose (FBG)> or =6.2 mmol/L, n=42. the hypoglycemia group: FBG 3.1-6.2 mmol/L, n=14], and 20 normal healthy controls [the control group, FBG (5.49+/-1.06) mmol/L)] were also included in the study. All patients had complete data of FBG, C-reactive protein (CRP), albumin (ALB), Leptin, fasting serum insulin (FISN), counting insulin sensitivity index (ISI), and pulmonary function tests [forced expiratory volume in one second (FEV1), FEV1 in percentage of forced vital capacity (FEV1/FVC), peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), total respiratory impedance (Zrs), airway resistance at 5, 20 Hz (R5, R20), airway resistance of capacitance and inertance at 5, 20 Hz (X5, X20), core resistance (Rc), periphery resistance (Rp), frequency resonant (Fres)]. The FBG, FISN, CRP were significantly higher and body mass index (BMI), ALB, ISI were significantly lower in the hyperglycemia group compared with control group (all PLeptin level (P>0.05). However, BMI, ALB, Leptin, ISI were significantly decreased and CRP, FISN were significantly increased in hypoglycemia group compared with the control group (PLeptin, CRP were significantly higher and ISI was significantly lower in hyperglycemia group compared with the hypoglycemia group (all P0.05). The serum levels of Leptin was significantly positively correlated with Zrs, R5, R20, Rc, BMI (all P0.05). ISI had significant positive correlations with FEV1/FVC, FEV1, PEF, MMEF (PLeptin-insulin resistance may aggravate the impairment of pulmonary function, prolong the length of hospital stay in the patient with COPD.

  8. The changes of serum leptin and insulin contents in elderly male patients with obesity-related hypertension

    International Nuclear Information System (INIS)

    Zhan Hao; Huang Daijuan; Yuan Bin; He Yong; Zhang Yongxue

    2004-01-01

    To study the contents of serum leptin and insulin in elderly male patients with obesity-related hypertension, the levels of serum leptin and insulin in 21 normotensive cases and 41 hypertensive cases of them were determined by RIA. The results showed that the levels of serum leptin and insulin between hypertensives and normotensives in the non-obese groups were not significantly different (P>0.05). Compared with normotensives, the levels of serum leptin and insulin of hypertensives in the obese groups remarkably increased 1.8μg/L and 2.7 mIU/L respectively (P<0.01). The levels of serum leptin and insulin in the patients with obesity - related hypertension were markedly higher than those in the patients with non-obesity-related hypertension and elevated 2.7μg/L and 4.7mIU/L (P<0.01) respectively. Insulin-sensitivity index (ISI) successively decreased in the groups of HBPOb, NBPOb, HBPNOb and NBPNOb (relative ISI 0.50, 0.68, 0.92, 1 respectively). It is concluded that leptin-resistance and insulin-resistance exist in male elderly patients with obesity-related hypertension

  9. Leptin and Fasting Regulate Rat Gastric Glucose-Regulated Protein 58

    Directory of Open Access Journals (Sweden)

    Susana B. Bravo

    2011-01-01

    Full Text Available The stomach secretes a wide range of peptides with essential metabolic functions, and thereby plays an important role in the regulation of energy homeostasis. Disulfide isomerase glucose-regulated protein 58 (GRp58 is a molecular chaperone member of the endoplasmic reticulum (ER stress signaling pathway, which is a marker for human gastric cancer. Since GRp58 seems to be regulated by a phosphorylation/dephosphorylation pattern shift, we used the 2DE gel methodology and peptide mass fingerprinting-protein identification by means of MALDI-TOF mass spectrometry. We show that gastric mucosa GRp58 is dephosphorylated by fasting, and this effect is blunted when fasted rats are treated with leptin. Furthermore, we assessed the gene expression of GRp58 under different physiological settings known to be associated with energy homeostasis (fasting, leptin treatment and leptin deficiency. We found that intraperitoneal administration of leptin increases whereas leptin deficiency decreases GRp58 mRNA levels. However, GRp58 expression remains unchanged after fasting, indicating that leptin actions on GRp58 are no direct sensitivity to fasting. Dissection of the molecular pathways mediating the interactions between ER stress-related factors and nutrient availability, as well as their target genes, may open a new avenue for the study of obesity and other metabolic disorders.

  10. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation.......The ability of glucose and insulin to modify insulin-stimulated glucose transport and uptake was investigated in perfused skeletal muscle. Here we report that perfusion of isolated rat hindlimbs for 5 h with 12 mM-glucose and 20,000 microunits of insulin/ml leads to marked, rapidly developing...

  11. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    , impairment of insulin action on muscle glucose transport and uptake. Thus maximal insulin-stimulated glucose uptake at 12 mM-glucose decreased from 34.8 +/- 1.9 to 11.5 +/- 1.1 mumol/h per g (mean +/- S.E.M., n = 10) during 5 h perfusion. This decrease in glucose uptake was accompanied by a similar change...... in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation....

  12. Programming of glucose-insulin homoeostasis

    DEFF Research Database (Denmark)

    Kongsted, Anna Hauntoft; Tygesen, M. P.; Husted, Sanne Vinter

    2014-01-01

    AIM: Exposure to adverse intra-uterine conditions can predispose for metabolic disorders later in life. By using a sheep model, we studied (i) how programming of glucose-insulin homoeostasis during late gestation is manifested later in life depending on the early post-natal dietary exposure and (ii......) whether dietary alteration in obese individuals can prevent adverse outcomes of early life programming. METHODS: During late gestation, twin-pregnant sheep were fed 100% (NORM) or 50% (LOW) of energy and protein requirements. After birth, offspring were exposed to a moderate (CONV) or high...

  13. Ingestion of carbohydrate-rich supplements during gestation programs insulin and leptin resistance but not body weight gain in adult rat offspring

    Directory of Open Access Journals (Sweden)

    Bernard eBeck

    2012-06-01

    Full Text Available Prenatal nutritional conditions can predispose to development of obesity and metabolic syndrome in adulthood. Gestation with its important hormonal status modification is a period of changes in usual feeding habits with pulses or avoidance for certain categories of food. We tried to mimic in an animal model some changes in food consumption patterns observed in pregnant women. For this purpose, Long-Evans female rats were fed during the dark period, their usual pre-gestational food quantity, and were allowed to complete their intake with either a control (Cr, high-fat (HF, or high-carbohydrate (HC diet available ad libitum during the light period. Dams fed a control diet ad libitum (Ca served as controls. Body weight and composition, food intake, and metabolic hormones (insulin, leptin were recorded in male offspring until 20 weeks after birth. Cr and HC females ate less than Ca females ( -16%; p<0.001 and their offspring presented a weight deficit from birth until 6 (HC group and 10 (Cr group weeks of age (p<0.05 or less. Plasma leptin corresponded to low body weight in Cr offspring, but was increased in HC offspring that in addition, had increased plasma insulin, blood glucose and subcutaneous adipose tissue mass. HF dams ate more than Ca dams (+13%;p<0.001, but plasma leptin and insulin were similar in their offspring. Hypothalamic Ob-Rb expression was increased in Cr, HC and HF offspring (+33-100% vs. Ca; p<0.05 or less. HC supplement ingestion during gestation leads therefore to insulin and leptin resistance in adult offspring independently of lower birth weight. These hormonal changes characterize obesity-prone animals. We therefore suggest to be heedful of the carbohydrate content in the diet during the last weeks (or months preceding delivery to limit development of later metabolic disorders in offspring.

  14. Comparison of serum leptin, glucose, total cholesterol and total protein levels in fertile and repeat breeder cows

    Directory of Open Access Journals (Sweden)

    Saime Guzel

    2014-12-01

    Full Text Available In the present study we measured serum glucose, leptin, total cholesterol and total protein concentrations in repeat breeder cows and compared them with fertile cows. For this aim, 20 repeat breeder cows and 20 fertile cows were used as material. Repeat breeder cows were found to have lower levels of leptin and glucose as compared with fertile ones. No significant differences in total cholesterol and total protein levels were observed between the two groups. No significant correlation of leptin with glucose, total cholesterol and total protein was observed in fertile and repeat breeder cows. Low concentrations of glucose and leptin can have some effects on reproductive problems as repeat breeder and help to understand potential mechanisms impairing fertility in repeat breeder cows.

  15. Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul S

    2016-01-01

    transporter protein 4 (GLUT4) to the plasma membrane which leads to facilitated diffusion of glucose into the cell. Understanding the precise signaling events guiding insulin-stimulated glucose uptake is pivotal, because impairment in these signaling events leads to development of insulin resistance and type...... 2 diabetes. This review summarizes current understanding of insulin signaling pathways mediating glucose uptake in healthy and insulin-resistant skeletal muscle.......Skeletal muscle is the largest tissues in the human body and is considered the primary target for insulin-stimulated glucose disposal. In skeletal muscle, binding of the insulin to insulin receptor (IR) initiates a signaling cascade that results in the translocation of the insulin-sensitive glucose...

  16. Pancreatic islets of variable size - insulin secretion and glucose utilization

    International Nuclear Information System (INIS)

    Colella, R.M.; Bonner-Weir, S.; Braunstein, L.P.; Schwalke, M.; Weir, G.C.

    1985-01-01

    Glucose metabolism and insulin secretion were studied in isolated rat pacreatic islets of different sizes and the amount of tissue was quantitated by the measurement of DNA. It was found that larger islets (140-210 ng DNA/islet) utilized more glucose (based on the conversion of 3 H-5-glucose to 3 H 2 O) per ng of DNA than islets containing less DNA (60-120 ng/islet). However, the insulin secreted per ng of DNA in response to a given glucose concentration was the same in islets of all sizes. Also, the islet insulin and glucagon content when expressed in terms of DNA did not depend upon islet size. Thus, although glucose utilization rates expressed as a function of islet DNA content were greater in larger islets, no such relationship was found for glucose-induced insulin release or insulin and glucagon content. 17 reference, 1 figure, 3 tables

  17. Diagnostic utility of leptin and insulin-like growth factor binding ...

    African Journals Online (AJOL)

    modulate glucose and insulin homeostasis through activation in peripheral tissues [6]. The insulin-like growth factor (IGF) system has a highly conserved function in mammals and plays a critical role in energy metabolism and cell renewal in response to nutrients. IGF pathway is not only involved in cell growth in tissue ...

  18. Effects of intense cycling training on plasma leptin and adiponectin and its relation to insulin resistance.

    Science.gov (United States)

    Lakhdar, Nadia; Ben Saad, Helmi; Denguezli, Myriam; Zaouali, Monia; Zbidi, Abdelkrim; Tabka, Zouhair; Bouassida, Anissa

    2013-01-01

    Adiponectin, the most abundant protein secreted by white adipose tissue, is known for its involvement in insulin resistance (HOMA-R). The purpose of this investigation was to assess the effect of intense cycling training for six months on plasma concentrations of adiponectin and leptin and HOMA-R. Eight trained males non professional cyclists participated in this study. They completed two times maximal exercises separated by six months heavy cycling training. Blood samples were obtained before exercise, at the end and after 30 and 60 minutes of recovery. Before training, adiponectin concentrations were not significantly altered after maximal exercise, but plasma leptin levels decreased significantly at the end of exercise (-21.42%, p30.68%, p30 min of recovery) (14.10%, pcycling training don't affect adiponectin concentrations, but decreases the synthesis of leptin and HOMA-R and improves aerobic capacity. Furthermore, it appears that after 6 months heavy chronic exercise adiponectin is not associated with aerobic capacity and/or insulin resistance and/or body composition modifications.

  19. Ovarian acyclicity in zoo African elephants (Loxodonta africana) is associated with high body condition scores and elevated serum insulin and leptin.

    Science.gov (United States)

    Morfeld, Kari A; Brown, Janine L

    2016-04-01

    The purpose of the present study was to determine whether excessive body fat and altered metabolic hormone concentrations in the circulation were associated with ovarian acyclicity in the world's largest land mammal, the African elephant. We compared body condition, glucose, insulin and leptin concentrations and the glucose-to-insulin ratio (G:I) between cycling (n=23; normal 14-16 week cycles based on serum progestagens for at least 2 years) and non-cycling (n=23; consistent baseline progestagen concentrations for at least 2 years) females. A validated body condition score (BCS) index (five-point scale; 1=thinnest, 5=fattest) was used to assess the degree of fatness of the study elephants. The mean BCS of non-cycling elephants was higher than that of their cycling counterparts. There were differences in concentrations of serum metabolic biomarkers, with non-cycling elephants in the BCS 5 category having higher leptin and insulin concentrations and a lower G:I ratio than cycling BCS 5 females. Using 'non-cycling' as the outcome variable in regression models, high BCS was a strong predictor of a non-cycling status. This study provides the first evidence that ovarian acyclicity in zoo African elephants is associated with body condition indicative of obesity, as well as elevated, perturbed biomarkers of metabolic status.

  20. Acute up-regulation of the rat brain somatostatin receptor-effector system by leptin is related to activation of insulin signaling and may counteract central leptin actions.

    Science.gov (United States)

    Perianes-Cachero, A; Burgos-Ramos, E; Puebla-Jiménez, L; Canelles, S; Frago, L M; Hervás-Aguilar, A; de Frutos, S; Toledo-Lobo, M V; Mela, V; Viveros, M P; Argente, J; Chowen, J A; Arilla-Ferreiro, E; Barrios, V

    2013-11-12

    Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain

  1. Leptin and insulin growth factor 1: diagnostic markers of the refeeding syndrome and mortality.

    Science.gov (United States)

    Elnenaei, Manal O; Alaghband-Zadeh, Jamshid; Sherwood, Roy; Awara, Mahmoud A; Moniz, Caje; le Roux, Carel W

    2011-09-01

    Refeeding syndrome is difficult to diagnose since the guidelines for identifying those at risk are largely based on subjective clinical parameters and there are no predictive biochemical markers. We examined the suitability of insulin-like growth factor 1 (IGF1) and leptin as markers to identify patients at risk of the refeeding syndrome before initiation of parenteral nutrition (PN). A total of thirty-five consecutive patients referred for commencement of PN were included. Serum leptin and IGF1 were measured before starting PN. Electrolytes, liver and renal function tests were conducted before and daily for 1 week after initiating PN. The primary outcome was a decrease in phosphate 12-36 h after initiating PN. 'Refeeding index' (RI) was defined as leptin × IGF1 divided by 2800 to produce a ratio of 1·0 in patients who are well nourished. RI had better sensitivity (78 %; 95 % CI 40, 97 %) and specificity (78 %; 95 % CI 40, 97 %) with a likelihood ratio of 3·4, at a cut-off value of 0·19 for predicting a ≥ 30 % decrease in phosphate concentration within 12-36 h after starting PN, compared with IGF1 or leptin alone. However, IGF1 was a better predictor of mortality than either leptin or the RI. The present study is the first to derive and test the 'RI', and find that it is a sensitive and specific predictor of the refeeding syndrome in hospitalised patients before starting PN.

  2. Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men.

    Directory of Open Access Journals (Sweden)

    Amy C Reynolds

    Full Text Available BACKGROUND: Sleep restriction is associated with development of metabolic ill-health, and hormonal mechanisms may underlie these effects. The aim of this study was to determine the impact of short term sleep restriction on male health, particularly glucose metabolism, by examining adrenocorticotropic hormone (ACTH, cortisol, glucose, insulin, triglycerides, leptin, testosterone, and sex hormone binding globulin (SHBG. METHODOLOGY/PRINCIPAL FINDINGS: N = 14 healthy men (aged 27.4±3.8, BMI 23.5±2.9 underwent a laboratory-based sleep restriction protocol consisting of 2 baseline nights of 10 h time in bed (TIB (B1, B2; 22:00-08:00, followed by 5 nights of 4 h TIB (SR1-SR5; 04:00-08:00 and a recovery night of 10 h TIB (R1; 22:00-08:00. Subjects were allowed to move freely inside the laboratory; no strenuous activity was permitted during the study. Food intake was controlled, with subjects consuming an average 2000 kcal/day. Blood was sampled through an indwelling catheter on B1 and SR5, at 09:00 (fasting and then every 2 hours from 10:00-20:00. On SR5 relative to B1, glucose (F(1,168 = 25.3, p<0.001 and insulin (F(1,168 = 12.2, p<0.001 were increased, triglycerides (F(1,168 = 7.5, p = 0.007 fell and there was no significant change in fasting homeostatic model assessment (HOMA determined insulin resistance (F(1,168 = 1.3, p = 0.18. Also, cortisol (F(1,168 = 10.2, p = 0.002 and leptin (F(1,168 = 10.7, p = 0.001 increased, sex hormone binding globulin (F(1,167 = 12.1, p<0.001 fell and there were no significant changes in ACTH (F(1,168 = 0.3, p = 0.59 or total testosterone (F(1,168 = 2.8, p = 0.089. CONCLUSIONS/SIGNIFICANCE: Sleep restriction impaired glucose, but improved lipid metabolism. This was associated with an increase in afternoon cortisol, without significant changes in ACTH, suggesting enhanced adrenal reactivity. Increased cortisol and reduced sex hormone binding globulin

  3. Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

    International Nuclear Information System (INIS)

    Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

    1982-01-01

    In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125 I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125 I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity

  4. Trichosanthes cucumerina extracts enhance glucose uptake and regulate adiponectin and leptin concentrations in 3T3-L1 adipocytes model

    Directory of Open Access Journals (Sweden)

    Sassi, A.,

    2017-10-01

    Full Text Available Trichosanthes cucumerina (Cucurbitaceae commonly known as Snake gourd or Labu Ular is considered the largest genre in the Cucurbitaceae family and is mainly found in the southeast areas of Asia. It has been used in Ayurvedic medicine as a treatment for certain diseases such as Diabetes mellitus, but these acclaims lack scientific-based evidence. In this study, water and ethanol extracts of three parts of Trichosanthes cucumerina namely; whole vegetable, peels, and seeds, were assessed for toxicity through a cell viability assay using 3T3-L1 pre-adipocytes model which revealed a maximum toleration concentration of 0.063 mg/mL. The extracts were further tested on adipocytes’ differentiation and positively showed a stimulation of lipid droplets formation during adipogenesis and significantly (p<0.001 increased glycerol release levels (75.34±3.69 μg/ml during adipolysis. The extracts also significantly (p<0.001 promoted the uptake of glucose into the cells (2636.22±91.33 Bq in an action similar to that of insulin. Similar results were observed during ELISA assay with a significant increase (p<0.001 in adiponectin concentrations (3593.1±225.25 ng/mL and a decrease in leptin concentrations (23870±5066.07 pg/mL. The present study results indicate a beneficial effect of Trichosanthes cucumerina extracts on adipogenesis, adipolysis and glucose uptake, in addition to a regulation of adiponectin and leptin concentrations in 3T3-L1 adipocytes which can be of clinical importance in energy regulation which is a key factor in treating diabetes, obesity, and metabolic syndrome.

  5. Serum leptin levels in children and adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index

    DEFF Research Database (Denmark)

    Kiess, W; Anil, M; Blum, W F

    1998-01-01

    The ob protein, termed leptin, is produced by adipocytes and is thought to act as an afferent satiety signal regulating weight through suppressing appetite and stimulating energy expenditure in humans and/or rodents. Insulin has been found to be a potent stimulator of leptin expression in rodents....... It is unclear at present whether this insulin action is a direct or an indirect effect. To investigate whether leptin concentrations in children and adolescents with type 1 diabetes (IDDM) were related to metabolic status, body weight, body mass index and insulin treatment, we have measured leptin...

  6. Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men.

    OpenAIRE

    Castillo, C; Bogardus, C; Bergman, R; Thuillez, P; Lillioja, S

    1994-01-01

    Insulin action and obesity are both correlated with the density of muscle capillary supply in humans. Since the altered muscle anatomy in the obese might affect interstitial insulin concentrations and reduce insulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower limb averaged only 34% of art...

  7. Effect of fat supplementation on leptin, insulin-like growth factor I, growth hormone, and insulin in cattle.

    Science.gov (United States)

    Becú-Villalobos, Damasia; García-Tornadú, Isabel; Shroeder, Guillermo; Salado, Eloy E; Gagliostro, Gerardo; Delavaud, Carole; Chilliard, Yves; Lacau-Mengido, Isabel M

    2007-07-01

    We investigated the effect of fat supplementation on plasma levels of hormones related to metabolism, with special attention to leptin, in cows in early lactation and in feedlot steers. In experiment 1, 34 lactating cows received no fat or else 0.5 or 1.0 kg of partially hydrogenated oil per day in addition to their basal diet from day 20 before the expected calving date to day 70 postpartum. In experiment 2, part of the corn in the basal concentrate was replaced with 0.7 kg of the same oil such that the diets were isocaloric; 18 cows received the fat-substituted diet and 18 a control diet from day 20 before the expected calving date to day 75 postpartum. In experiment 3, calcium salts of fatty acids were added to the basal diet of 14 feedlot steers for 80 d; another 14 steers received a control diet. The basal plasma levels of leptin were higher in the cows than in the steers. Dietary fat supplementation did not affect the leptin levels in the lactating cows but lowered the levels in the feedlot steers despite greater energy intake and body fatness (body weight) in the steers receiving the supplement than in those receiving the control diet. The levels of insulin-like growth factor I and insulin were decreased with dietary fat supplementation in the lactating cows but were unaffected in the steers, suggesting that responses to fat ingestion depend on the physiological state of the animal, including age and sex. Finally, no effects of supplementary fat on the level of growth hormone were demonstrated in any of the models.

  8. Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

    Science.gov (United States)

    Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

    2011-01-01

    OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

  9. Acute insulin-induced elevations of circulating leptin and feeding inhibition in lean but not obese rats.

    Science.gov (United States)

    Singh, Kimberly A; Boozer, Carol N; Vasselli, Joseph R

    2005-08-01

    Insulin has been shown to stimulate leptin mRNA expression acutely in rat adipose tissue, but its short-term effects on circulating leptin levels, and subsequent feeding behavior, have not been well described. We used 11-mo-old female selectively bred obesity-resistant (OR) and obesity-prone (OP) Sprague-Dawley rats maintained on laboratory chow to investigate this question. At testing, body weights and basal leptin levels of the OP rats were significantly elevated compared with the OR rats. In the 3-h fasted state, injection of 2.0 U insulin/kg ip resulted in significant elevations of plasma leptin at 4 h postinjection in both OP and OR groups (hour 4, +2.50 and +5.98 ng/ml, respectively). In separate feeding tests with the same groups, intake of laboratory chow pellets was significantly inhibited during hours 2-4 after 2.0 U/kg of insulin in the OR (-80.1%, P < 0.05), but not in the OP group, compared with intake after saline injections. In feeding tests with palatable moderately high-fat pellets after 2.0 and 3.0 U insulin/kg ip, significant decreases between hours 2 and 4 in intake were seen in the OR group only (-41.0 and -68.3%, respectively). Thus feeding inhibition coincides with insulin-induced elevations of plasma leptin in lean but not obese Sprague-Dawley rats. Our data suggest that elevations of leptin within the physiological range may contribute to short-term inhibition of food intake in rats and that this process may be stimulated by feeding-related insulin release.

  10. Glucose lowering effects of inhaled insulin in healthy cats.

    Science.gov (United States)

    DeClue, Amy E; Leverenz, Elizabeth F; Wiedmeyer, Charles E; Bryan, Margaret E; Reinero, Carol R

    2008-10-01

    Inhaled medications have proven effective and well tolerated in cats, and inhaled insulin has been used successfully for the management of diabetes mellitus in humans. Thus, we hypothesize that delivery of aerosolized regular insulin can lower blood glucose in healthy cats. Five adult cats were administered aerosolized 0.9% saline (IS), regular insulin intravenously (IV) 0.5 U/kg, and aerosolized regular insulin 15 U/kg (I15) and 25 U/kg (I25) and blood glucose was evaluated. Mean blood glucose was significantly lower at 15, 30 and 45 min in the I25 and IV groups compared to baseline. Similarly, the IV and I25 groups had a significantly greater maximal percent change in blood glucose than the IS group. Significantly more cats developed severe hypoglycemia (glucose concentrations in healthy cats.

  11. LEPTIN AND OBESITY – NEUROENDOCRINE , METABOLIC AND ATHEROGENIC EFFECTS OF LEPTIN

    Directory of Open Access Journals (Sweden)

    Mišo Šabovič

    2003-01-01

    Full Text Available Background. Leptin is an adipocyte-derived hormone that was recently discovered. Leptin and leptin resistance play an important role in the pathogenesis of obesity. Leptin acts by binding to specific receptors in the hypothalamus to alter the expression of several neuropeptides that regulate food intake and energy expenditure. As commonly found, obese persons have leptin resistance and consequently attenuated effects of leptin. Mechanism underlying leptin resistance has not been explained yet: it might be the result of a receptor or post receptor defect, impaired transport of leptin through cerebrovascular barrier or inactivation of leptin by binding proteins. Phase I and II clinical trials proved that recombinant leptin administration to humans is safe. First results of the current phase III clinical trials demonstrated that leptin is moderately effective in the treatment of obesity.Conclusions. Beside anti-obesity effect, leptin can have important metabolic and neuroendocrine effects. It is involved in glucose metabolism and insulin secretion, pathogenesis of polymetabolic syndrome, diabetes and arterial hypertension. In addition it affects some processes of atherothrombosis. It interacts with and significantly influences hypothalamic-pituitaryadrenal, thyroid, sexual glands and growth hormone axes. Explaining the mechanism of leptin resistance could be important for understanding the pathogenesis of obesity and associated pathologic states as polymetabolic syndrom, diabetes, arterial hipertension and atherothrombosis.

  12. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles.

    Science.gov (United States)

    Jessen, N; Selmer Buhl, E; Pold, R; Schmitz, O; Lund, S

    2008-04-01

    Type 2 diabetes is preceded by the presence of skeletal muscle insulin resistance, and drugs that increase insulin sensitivity in skeletal muscle prevent the disease. S15511 is an original compound with demonstrated effects on insulin sensitivity in animal models of insulin resistance. However, the mechanisms behind the insulin-sensitizing effect of S15511 are unknown. The aim of our study was to explore whether S15511 improves insulin sensitivity in skeletal muscles. Insulin sensitivity was assessed in skeletal muscles from S15511-treated rats by measuring intracellular insulin-signaling activity and insulin-stimulated glucose transport in isolated muscles. In addition, GLUT4 expression and glycogen levels were assessed after treatment. S15511 treatment was associated with an increase in insulin-stimulated glucose transport in type IIb fibers, while type I fibers were unaffected. The enhanced glucose transport was mirrored by a fiber type-specific increase in GLUT4 expression, while no improvement in insulin-signaling activity was observed. S15511 is a novel insulin sensitizer that is capable of improving glucose homeostasis in nondiabetic rats. The compound enhances skeletal muscle insulin sensitivity and specifically targets type IIb muscle fibers by increasing GLUT4 expression. Together these data show S15511 to be a potentially promising new drug in the treatment and prevention of type 2 diabetes.

  13. Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease

    OpenAIRE

    Kythreotis, Prokopis; Kokkini, Ageliki; Avgeropoulou, Stavrina; Hadjioannou, Argyro; Anastasakou, Efgenia; Rasidakis, Antonis; Bakakos, Petros

    2009-01-01

    Abstract Background Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α). Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH). The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD). The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether the...

  14. Ethnic variation in adiponectin and leptin levels and their association with adiposity and insulin resistance.

    Science.gov (United States)

    Mente, Andrew; Razak, Fahad; Blankenberg, Stefan; Vuksan, Vlad; Davis, A Darlene; Miller, Ruby; Teo, Koon; Gerstein, Hertzel; Sharma, Arya M; Yusuf, Salim; Anand, Sonia S

    2010-07-01

    To investigate ethnic differences in adiponectin and leptin concentration and to determine whether these adipokines and a high-glycemic index diet account for ethnic variation in insulin resistance. In 1,176 South Asian, Chinese, Aboriginal, and European Canadians, fasting blood samples were drawn, and clinical history and dietary habits including glycemic index/glycemic load were recorded using standardized questionnaires. Insulin resistance was defined using homeostasis model assessment-insulin resistance (HOMA-IR). Adiponectin concentrations were significantly higher in Europeans (adjusted mean 12.94 [95% CI 2.27-13.64]) and Aboriginal people (11.87 [11.19-12.59]) than in South Asians (9.35 [8.82-9.92]) and Chinese (8.52 [8.03-9.03]) (overall P < 0.001). Serum leptin was significantly higher in South Asians (11.82 [10.72-13.04]) and Aboriginal people (11.13 [10.13-12.23]) than in Europeans (9.21 [8.38-10.12]) and Chinese (8.25 [7.48-9.10]). BMI and waist circumference were inversely associated with adiponectin in every group except the South Asians (P < 0.001 for interaction). Adiponectin was inversely and leptin was positively associated with HOMA-IR (P < 0.001). The increase in HOMA-IR for each given decrease in adiponectin was larger among South Asians (P = 0.01) and Aboriginal people (P < 0.001) than among Europeans. A high glycemic index was associated with a larger decrease in adiponectin among South Asians (P = 0.03) and Aboriginal people (P < 0.001) and a larger increase in HOMA-IR among South Asians (P < 0.05) relative to that in other groups. South Asians have the least favorable adipokine profile and, like the Aboriginal people, display a greater increase in insulin resistance with decreasing levels of adiponectin. Differences in adipokines and responses to glycemic foods parallel the ethnic differences in insulin resistance.

  15. Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption.

    Science.gov (United States)

    Bernardo, Ana Paula; Oliveira, Jose C; Santos, Olivia; Carvalho, Maria J; Cabrita, Antonio; Rodrigues, Anabela

    2015-12-07

    Insulin resistance has been associated with cardiovascular disease in peritoneal dialysis patients. Few studies have addressed the impact of fast transport status or dialysis prescription on insulin resistance. The aim of this study was to test whether insulin resistance is associated with obesity parameters, peritoneal transport rate, and glucose absorption. Insulin resistance was evaluated with homeostasis model assessment method (HOMA-IR), additionally corrected by adiponectin (HOMA-AD). Enrolled patients were prevalent nondiabetics attending at Santo António Hospital Peritoneal Dialysis Unit, who were free of hospitalization or infectious events in the previous 3 months (51 patients aged 50.4 ± 15.9 years, 59% women). Leptin, adiponectin, insulin-like growth factor-binding protein 1 (IGFBP-1), and daily glucose absorption were also measured. Lean tissue index, fat tissue index (FTI), and relative fat mass (rel.FM) were assessed using multifrequency bioimpedance. Patients were categorized according to dialysate to plasma creatinine ratio at 4 hours, 3.86% peritoneal equilibration test, and obesity parameters. Obesity was present in 49% of patients according to rel.FM. HOMA-IR correlated better with FTI than with body mass index. Significant correlations were found in obese, but not in nonobese patients, between HOMA-IR and leptin, leptin/adiponectin ratio (LAR), and IGFBP-1. HOMA-IR correlated with HOMA-AD, but did not correlate with glucose absorption or transport rate. There were no significant differences in insulin resistance indices, glucose absorption, and body composition parameters between fast and nonfast transporters. A total of 18 patients (35.3%) who had insulin resistance presented with higher LAR and rel.FM (7.3 [12.3, interquartile range] versus 0.7 [1.4, interquartile range], Pinsulin resistance. FTI and LAR were independent correlates of HOMA-IR in multivariate analysis adjusted for glucose absorption and small-solute transport (r=0

  16. Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

    Science.gov (United States)

    Oh, Da Hee; Kim, Jung Yeon; Lee, Bong Gn; You, Jeong Soon; Chang, Kyung Ja; Chung, Hyunju; Yoo, Myung Chul; Yang, Hyung-In; Kang, Ja-Heon; Hwang, Yoo Chul; Ahn, Kue Jeong; Chung, Ho-Yeon

    2012-01-01

    This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve β-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients. PMID:23114424

  17. Insulin resistance in human subjects having impaired glucose regulation

    International Nuclear Information System (INIS)

    Khan, S.H.; Khan, F.A.; Ijaz, A.

    2007-01-01

    To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

  18. Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome.

    Science.gov (United States)

    Ducluzeau, Pierre-Henri; Cousin, Patrice; Malvoisin, Etienne; Bornet, Hubert; Vidal, Hubert; Laville, Martine; Pugeat, Michel

    2003-08-01

    Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best

  19. Importance of peripheral insulin levels for insulin-induced suppression of glucose production in depancreatized dogs.

    OpenAIRE

    Giacca, A; Fisher, S J; Shi, Z Q; Gupta, R; Lickley, H L; Vranic, M

    1992-01-01

    It is generally believed that glucose production (GP) cannot be adequately suppressed in insulin-treated diabetes because the portal-peripheral insulin gradient is absent. To determine whether suppression of GP in diabetes depends on portal insulin levels, we performed 3-h glucose and specific activity clamps in moderately hyperglycemic (10 mM) depancreatized dogs, using three protocols: (a) 54 pmol.kg-1 bolus + 5.4 pmol.kg-1.min-1 portal insulin infusion (n = 7; peripheral insulin = 170 +/- ...

  20. Effects of insulin and leptin in the ventral tegmental area and arcuate hypothalamic nucleus on food intake and brain reward function in female rats.

    Science.gov (United States)

    Bruijnzeel, Adrie W; Corrie, Lu W; Rogers, Jessica A; Yamada, Hidetaka

    2011-06-01

    There is evidence for a role of insulin and leptin in food intake, but the effects of these adiposity signals on the brain reward system are not well understood. Furthermore, the effects of insulin and leptin on food intake in females are underinvestigated. These studies investigated the role of insulin and leptin in the ventral tegmental area (VTA) and the arcuate hypothalamic nucleus (Arc) on food intake and brain reward function in female rats. The intracranial self-stimulation procedure was used to assess the effects of insulin and leptin on the reward system. Elevations in brain reward thresholds are indicative of a decrease in brain reward function. The bilateral administration of leptin into the VTA (15-500 ng/side) or Arc (15-150 ng/side) decreased food intake for 72 h. The infusion of leptin into the VTA or Arc resulted in weight loss during the first 48 (VTA) or 24 h (Arc) after the infusions. The administration of insulin (0.005-5 mU/side) into the VTA or Arc decreased food intake for 24 h but did not affect body weights. The bilateral administration of low, but not high, doses of leptin (15 ng/side) or insulin (0.005 mU/side) into the VTA elevated brain reward thresholds. Neither insulin nor leptin in the Arc affected brain reward thresholds. These studies suggest that a small increase in leptin or insulin levels in the VTA leads to a decrease in brain reward function. A relatively large increase in insulin or leptin levels in the VTA or Arc decreases food intake. Published by Elsevier B.V.

  1. Effects of turtle oil on insulin sensitivity and glucose metabolism in insulin resistant cell model

    International Nuclear Information System (INIS)

    Bai Jing; Tian Yaping; Guo Duo

    2007-01-01

    To evaluate the effects of turtle oil on insulin sensitivity and glucose metabolism in an insulin-resistant (IR) cell model which was established by the way of high concentration of insulin induction with HepG 2 cell in vitro culture. The IR cells were treated by turtle oil, the glucose consumption and 3 H-D-glucose incorporation rate in IR cells were detected by the way of glucose oxidase and 3 H-D-glucose incorporation assay respectively. The state of cell proliferation was tested by MTT method. The results showed that the incorporation rate of 3 H-D-glucose in IR cells was significantly lower than that in the control cells(P 3 H-D-glucose incorporation rate in either IR cells or control cells was increased with the increase of insulin concentration. Moreover, the 3 H-D-glucose incorporation rate of IR cells increased slower than that of control cells. The MTT assay showed that turtle oil can promote the proliferation of IR cell and control cell. The glucose uptake and glucose consumption in IR cell which treated with turtle oil was significantly increase than that in the control cells (P<0.05). Turtle oil can improve the insulin sensitivity and glucose metabolism in the IR cell model. (authors)

  2. Blueberries’ Impact on Insulin Resistance and Glucose Intolerance

    Directory of Open Access Journals (Sweden)

    April J. Stull

    2016-11-01

    Full Text Available Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM. These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by homeostatic model assessment-estimated insulin resistance (HOMA-IR, insulin tolerance tests, and hyperinsulinemic-euglycemic clamps. Additionally, the improvements in glucose tolerance after blueberry consumption were assessed by glucose tolerance tests. However, firm conclusions regarding the anti-diabetic effect of blueberries cannot be drawn due to the small number of existing clinical studies. Although the current evidence is promising, more long-term, randomized, and placebo-controlled trials are needed to establish the role of blueberries in preventing or delaying T2DM.

  3. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes.

    Science.gov (United States)

    Satin, Leslie S; Butler, Peter C; Ha, Joon; Sherman, Arthur S

    2015-04-01

    Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern, has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

    Science.gov (United States)

    Satin, Leslie S.; Butler, Peter C.; Ha, Joon; Sherman, Arthur S.

    2015-01-01

    Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. PMID:25637831

  5. Restraint stress impairs glucose homeostasis through altered insulin ...

    African Journals Online (AJOL)

    The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the rats were ...

  6. Leptin and insulin in the seminal plasma of zebu bulls in peripuberty

    Directory of Open Access Journals (Sweden)

    Fernando Andrade Souza

    2012-04-01

    Full Text Available In order to determine the profile of leptin and insulin values in seminal plasma and their correlations with sperm patterns during the peripuberty, a total of 16 crossbred Gyr dairy bulls were monitored from 60 days before to 60 days after puberty, separated into two groups, early and regular, according to the onset of puberty. Hormone values were determined by radioimmunoassay after gel filtration in fast performance liquid chromatography and semen patterns, according to the Brazilian College of Animal Reproduction. Insulin concentrations in seminal plasma did not differ between groups, nor between the ages, with the pooling of the data showing average of 35.15±16.93, 36.60±26.21, 26.82±09.81, and 43.56±31.71 32.24±16.71 U/mL for the pubertal period of -60, -30, 0, +30 and +60 days, respectively. These values were not correlated with sperm parameters, but differed in the group of animals with the highest percentage of major defects (31.08±18.58 U/mL compared with those with lower percentage of these sperm defects (40.01±25.37 U/mL. Leptin was not correlated with sperm parameters and did not differ between groups or stage of sexual development, with concentrations of 23.10±10.43, 24.35±9.42, 22.41±9.90, 23.76±9.69 and 24.99±11.42 ng/mL for the periods of puberty aforementioned, respectively, after being grouped. These results demonstrated the binding of insulin to the structural quality of the sperm cell, and this hormone is indicated in andrologycal evaluation of future breeding soundness.

  7. DEFECTS IN INSULIN-SECRETION IN NIDDM - B-CELL GLUCOSE INSENSITIVITY OR GLUCOSE TOXICITY

    NARCIS (Netherlands)

    VANHAEFTEN, TW

    In NIDDM, first-phase insulin release to glucose is (almost) absent. However, in contrast to older studies which suggested that in NIDDM the B-cell is ''blind'' for glucose, recent evidence indicates that the B-cell is not insensitive for glucose as far as second phase release is concerned. This

  8. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.

    Science.gov (United States)

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W; Pfluger, Paul T; Fernandez, Ana M; Luquet, Serge; Woods, Stephen C; Torres-Alemán, Ignacio; Kahn, C Ronald; Götz, Magdalena; Horvath, Tamas L; Tschöp, Matthias H

    2016-08-11

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients.

    Science.gov (United States)

    Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik; Lauritzen, Torsten; Christiansen, Jens Sandahl; Laursen, Torben

    2015-05-01

    Little is known about the influence of exogenous insulin and actual glucose levels on the release of endogenous insulin in insulin-treated type 2 diabetes mellitus (T2DM) patients. This study investigated the interaction among serum endogenous insulin (s-EI), serum exogenous insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m(2)) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU/h) as a continuous subcutaneous insulin infusion (CSII) during a 10-h period on two occasions with different duration of hyperglycemia: (1) transient hyperglycemia for 2 h (visit TH) and (2) continuous hyperglycemia for 12 h (visit CH). During steady state the variances of plasma glucose (p-glucose), s-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first 100 min of both visits when s-IAsp was undetectable (adjusted R(2)=0.9). A complex but statistically significant interaction among s-IAsp, s-EI, p-glucose, and patients was observed during measurable s-IAsp levels (adjusted R(2)=0.70). Endogenous and exogenous insulin showed higher variation during continuous hyperglycemia. Significantly lower levels of exogenous insulin were observed following CSII during continuous hyperglycemia compared with transient hyperglycemia. Endogenous insulin levels could in a complex way be explained by an individual interaction among p-glucose and serum exogenous insulin, if present.

  10. Inhaled insulin for controlling blood glucose in patients with diabetes

    Directory of Open Access Journals (Sweden)

    Bernard L Silverman

    2008-01-01

    Full Text Available Bernard L Silverman1, Christopher J Barnes2, Barbara N Campaigne3, Douglas B Muchmore31Alkermes, Inc, Cambridge, MA, USA; 2i3 Statprobe, Ann Arbor, MI; 3Eli Lilly and Company, Indianapolis, IN, USAAbstract: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.Keywords: diabetes, inhaled insulin, cardiovascular disease, blood glucose

  11. Importance of peripheral insulin levels for insulin-induced suppression of glucose production in depancreatized dogs.

    Science.gov (United States)

    Giacca, A; Fisher, S J; Shi, Z Q; Gupta, R; Lickley, H L; Vranic, M

    1992-01-01

    It is generally believed that glucose production (GP) cannot be adequately suppressed in insulin-treated diabetes because the portal-peripheral insulin gradient is absent. To determine whether suppression of GP in diabetes depends on portal insulin levels, we performed 3-h glucose and specific activity clamps in moderately hyperglycemic (10 mM) depancreatized dogs, using three protocols: (a) 54 pmol.kg-1 bolus + 5.4 pmol.kg-1.min-1 portal insulin infusion (n = 7; peripheral insulin = 170 +/- 51 pM); (b) an equimolar peripheral infusion (n = 7; peripheral insulin = 294 +/- 28 pM, P dogs at 10 mM glucose, GC was threefold higher than normal but failed to decrease with insulin infusion by either route. Glycerol, alanine, FFA, and glucagon levels decreased proportionally to peripheral insulinemia. However, the decrease in glucagon was not significantly greater in protocol 2 than in 1 or 3. When we combined all protocols, we found a correlation between the decrements in glycerol and FFAs and the decrease in GP (r = 0.6, P dogs, suppression of GP appears to be more dependent on peripheral than portal insulin concentrations and may be mainly mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and by the suppressive effect of insulin on glucagon secretion. These results suggest that a portal-peripheral insulin gradient might not be necessary to effectively suppress postprandial GP in insulin-treated diabetics. PMID:1430203

  12. Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Kythreotis, Prokopis; Kokkini, Ageliki; Avgeropoulou, Stavrina; Hadjioannou, Argyro; Anastasakou, Efgenia; Rasidakis, Antonis; Bakakos, Petros

    2009-04-05

    Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-alpha). Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH). The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD). The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation. We measured serum leptin, IGF-I, TNF-alpha, interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema). Serum leptin and IGF-I were measured by radioimmunoassay and TNF-alpha, IL-1 beta, IL-6 and IL-8 were measured by ELISA. Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p leptin and TNF-alpha on Day 1 (r = 0.620, p leptin levels along with decreased IGF-I levels occurred during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.

  13. Insulin signalling and the regulation of glucose and lipid metabolism

    Science.gov (United States)

    Saltiel, Alan R.; Kahn, C. Ronald

    2001-12-01

    The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.

  14. Polysomnographic sleep, growth hormone insulin-like growth factor-I axis, leptin, and weight loss

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Wildschiødtz, Gordon; Juul, Anders

    2008-01-01

    severely obese subjects (BMI: 41+/-1 kg/m(2), 32+/-2 years of age), cross-sectional at baseline, and longitudinal after a dramatically diet-induced weight loss (36+/-7 kg). Ten age- and gender-matched nonobese subjects served as controls. Sleep duration (360+/-17 vs. 448+/-15 min/night; P... compared with nonobese subjects After diet-induced weight loss the differences in GH, free IGF-I, and leptin were no longer present between previously obese and nonobese subjects, whereas a significant difference in sleep duration and total IGF-I levels persisted. Rapid eye movement (REM) sleep, non......Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have...

  15. Leptin-to-Adiponectin Ratio is Related to Low Grade Inflammation and Insulin Resistance Independent of Obesity in Non-Diabetic Taiwanese: A Cross-Sectional Cohort Study

    Science.gov (United States)

    Chou, Hsin-Hua; Hsu, Lung-An; Wu, Semon; Teng, Ming-Sheng; Sun, Yu-Chen; Ko, Yu-Lin

    2014-01-01

    Background Leptin and adiponectin are secreted from adipose tissue and exert opposing effects on C-reactive protein (CRP) levels and insulin resistance. As hypertrophic adipocytes secrete more leptin and less adiponectin, the leptin-to adiponectin ratio (LAR) has been proposed as a useful measure of insulin resistance and vascular risk. We investigated whether LAR may serve as a better predictor than either leptin or adiponectin alone for low-grade inflammation and insulin resistance independent of obesity in a non-diabetic Taiwanese population. Methods This study included 568 non-diabetic Taiwanese individuals (297 men, 271 women). CRP, leptin and adiponectin were measured using enzyme-linked immunosorbent assay. The degree of insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). Results In the receiver operator characteristic analysis, the area under the curve of LAR in predicting individuals with elevated CRP and insulin resistance was significantly greater than that for either leptin (p = 0.0035 vs. elevated CRP, p HOMA-IR index (p HOMA-IR are greater than the association with leptin or adiponectin alone. PMID:27122790

  16. Plasma concentrations of leptin, insulin-like growth factor-I, and insulin in relation to changes in body condition score in heifers.

    Science.gov (United States)

    León, H V; Hernández-Cerón, J; Keislert, D H; Gutierrez, C G

    2004-02-01

    The objective of this study was to determine the relationships among plasma concentrations of leptin, insulin, and IGF-I with dynamic changes in body condition scores (BCS) in heifers. Nineteen Zebu-Brown Swiss crossbred heifers, 24 to 30 mo old, weighing 322 +/- 9 kg, and with an initial BCS of 2.6 +/- 0.11 (range = 1 to 9) were used. Heifers were fed 60% of their maintenance requirements until they reached a BCS of Heifers were then maintained at that level for 25 d, after which they were fed to gain 1 kg of body weight daily until a BCS of 6 was reached. Heifers were weighed weekly and BCS was measured every 2 wk. Plasma samples were collected twice weekly, and leptin and insulin were determined by RIA. An immunoradiometric assay was used to measure IGF-I from one sample every 2 wk. Plasma concentrations of leptin were positively correlated during nutritional restriction (NR) and weight gain (WG) periods with BCS (r = 0.47 for NR, and r = 0.83 for WG; P weight (r = 0.40 for NR, and r = 0.78 for WG; P weight gain, leptin concentration increased at BCS 3 and thereafter for each integer change in the BCS. Regression analysis showed that changes in body weight affect leptin concentrations within a given BCS. There was a decrease in IGF-I as BCS declined (P weight gain, by contrast, IGF-I increased significantly (P heifers with BCS 1 (P heifers of BCS 2 and 3, insulin did not differ and was lower than in heifers of BCS 1 (P heifers at BCS 4 to 6. Leptin was positively correlated (P heifers, as well as an indicator of nutritional status.

  17. Insulin secretion and incretin hormones after oral glucose in non-obese subjects with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Rask, E; Olsson, T; Söderberg, S

    2004-01-01

    Subjects with impaired glucose tolerance (IGT) are usually overweight and exhibit insulin resistance with a defective compensation of insulin secretion. In this study, we sought to establish the interrelation between insulin secretion and insulin sensitivity after oral glucose in non-obese subjects...... with IGT and we also examined this interrelation in relation to the 2 main incretins, glucagon-like peptide (GLP-1) and gastric inhibitory polypeptide (GIP). To that end, 13 women with IGT and 17 women with normal glucose tolerance (NGT) underwent an oral glucose tolerance test (OGTT) with measurements...... of glucose, insulin, C-peptide, GLP-1, and GIP. Insulin secretion (TIS) and insulin sensitivity (OGIS) were assessed using models describing the relationship between glucose, insulin and C-peptide data. These models allowed estimation also of the hepatic extraction of insulin. The age (54.2 +/- 9.7 [mean...

  18. Estimation of insulin secretion, glucose uptake by tissues, and liver handling of glucose using a mathematical model of glucose-insulin homeostasis in lean and obese mice.

    Science.gov (United States)

    Brenner, Michael; Abadi, Sakineh Esmaeili Mohsen; Balouchzadeh, Ramin; Lee, H Felix; Ko, Hoo Sang; Johns, Michael; Malik, Nehal; Lee, Joshua J; Kwon, Guim

    2017-06-01

    Destruction of the insulin-producing β-cells is the key determinant of diabetes mellitus regardless of their types. Due to their anatomical location within the islets of Langerhans scattered throughout the pancreas, it is difficult to monitor β-cell function and mass clinically. To this end, we propose to use a mathematical model of glucose-insulin homeostasis to estimate insulin secretion, glucose uptake by tissues, and hepatic handling of glucose. We applied the mathematical model by Lombarte et al. (2013) to compare various rate constants representing glucose-insulin homeostasis between lean (11% fat)- and high fat diet (HFD; 45% fat)-fed mice. Mice fed HFD (n = 12) for 3 months showed significantly higher body weights (49.97 ± 0.52 g vs. 29.86 ± 0.46 g), fasting blood glucose levels (213.08 ± 10.35 mg/dl vs. 121.91 ± 2.26 mg/dl), and glucose intolerance compared to mice fed lean diet (n = 12). Mice were injected with 1 g/kg glucose intraperitoneally and blood glucose levels were measured at various intervals for 120 min. We performed simulation using Arena™ software based on the mathematical model and estimated the rate constants (9 parameters) for various terms in the differential equations using OptQuest™. The simulated data fit accurately to the observed data for both lean and obese mice, validating the use of the mathematical model in mice at different stages of diabetes progression. Among 9 parameters, 5 parameters including basal insulin, k 2 (rate constant for insulin-dependent glucose uptake to tissues), k 3 (rate constant for insulin-independent glucose uptake to tissues), k 4 (rate constant for liver glucose transfer), and I pi (rate constant for insulin concentration where liver switches from glucose release to uptake) were significantly different between lean- and HFD-fed mice. Basal blood insulin levels, k 3 , and I pi were significantly elevated but k 2 and k 4 were reduced in mice fed a HFD compared to those fed a lean diet. Non

  19. TRPM5 regulates glucose-stimulated insulin secretion.

    Science.gov (United States)

    Brixel, Lili R; Monteilh-Zoller, Mahealani K; Ingenbrandt, Claudia S; Fleig, Andrea; Penner, Reinhold; Enklaar, Thorsten; Zabel, Bernhard U; Prawitt, Dirk

    2010-06-01

    Insulin secretion in beta-pancreatic cells due to glucose stimulation requires the coordinated alteration of cellular ion concentrations and a substantial membrane depolarization to enable insulin vesicle fusion with the cellular membrane. The cornerstones of this cascade are well characterized, yet current knowledge argues for the involvement of additional ion channels in this process. TRPM5 is a cation channel expressed in beta-cells and proposed to be involved in coupling intracellular Ca(2+) release to electrical activity and cellular responses. Here, we report that TRPM5 acts as an indispensable regulator of insulin secretion. In vivo glucose tolerance tests showed that Trpm5 (-/-) -mice maintain elevated blood glucose levels for over an hour compared to wild-type littermates, while insulin sensitivity is normal in Trpm5 (-/-) -mice. In pancreatic islets isolated from Trpm5 (-/-) -mice, hyperglycemia as well as arginine-induced insulin secretion was diminished. The presented results describe a major role for TRPM5 in glucose-induced insulin secretion beyond membrane depolarization. Dysfunction of the TRPM5 protein could therefore be an important factor in the etiology of some forms of type 2 diabetes, where disruption of the normal pattern of secretion is observed.

  20. Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance.

    Science.gov (United States)

    Wickenberg, Jennie; Lindstedt, Sandra; Berntorp, Kerstin; Nilsson, Jan; Hlebowicz, Joanna

    2012-06-01

    Previous studies on healthy subjects have shown that the intake of 6 g Cinnamomum cassia reduces postprandial glucose and that the intake of 3 g C. cassia reduces insulin response, without affecting postprandial glucose concentrations. Coumarin, which may damage the liver, is present in C. cassia, but not in Cinnamomum zeylanicum. The aim of the present study was to study the effect of C. zeylanicum on postprandial concentrations of plasma glucose, insulin, glycaemic index (GI) and insulinaemic index (GII) in subjects with impaired glucose tolerance (IGT). A total of ten subjects with IGT were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with placebo or C. zeylanicum capsules. Finger-prick capillary blood samples were taken for glucose measurements and venous blood for insulin measurements, before and at 15, 30, 45, 60, 90, 120, 150 and 180 min after the start of the OGTT. The ingestion of 6 g C. zeylanicum had no significant effect on glucose level, insulin response, GI or GII. Ingestion of C. zeylanicum does not affect postprandial plasma glucose or insulin levels in human subjects. The Federal Institute for Risk Assessment in Europe has suggested the replacement of C. cassia by C. zeylanicum or the use of aqueous extracts of C. cassia to lower coumarin exposure. However, the positive effects seen with C. cassia in subjects with poor glycaemic control would then be lost.

  1. Postprandial glucose and insulin profiles following a glucose-loaded meal in cats and dogs.

    Science.gov (United States)

    Hewson-Hughes, Adrian K; Gilham, Matthew S; Upton, Sarah; Colyer, Alison; Butterwick, Richard; Miller, Andrew T

    2011-10-01

    Data from intravenous (i.v.) glucose tolerance tests suggest that glucose clearance from the blood is slower in cats than in dogs. Since different physiological pathways are activated following oral administration compared with i.v. administration, we investigated the profiles of plasma glucose and insulin in cats and dogs following ingestion of a test meal with or without glucose. Adult male and female cats and dogs were fed either a high-protein (HP) test meal (15 g/kg body weight; ten cats and eleven dogs) or a HP + glucose test meal (13 g/kg body-weight HP diet + 2 g/kg body-weight D-glucose; seven cats and thirteen dogs) following a 24 h fast. Marked differences in plasma glucose and insulin profiles were observed in cats and dogs following ingestion of the glucose-loaded meal. In cats, mean plasma glucose concentration reached a peak at 120 min (10.2, 95 % CI 9.7, 10.8 mmol/l) and returned to baseline by 240 min, but no statistically significant change in plasma insulin concentration was observed. In dogs, mean plasma glucose concentration reached a peak at 60 min (6.3, 95 % CI 5.9, 6.7 mmol/l) and returned to baseline by 90 min, while plasma insulin concentration was significantly higher than pre-meal values from 30 to 120 min following the glucose-loaded meal. These results indicate that cats are not as efficient as dogs at rapidly decreasing high blood glucose levels and are consistent with a known metabolic adaptation of cats, namely a lack of glucokinase, which is important for both insulin secretion and glucose uptake from the blood.

  2. The over-expression of miR-200a in the hypothalamus of ob/ob mice is linked to leptin and insulin signaling impairment.

    Science.gov (United States)

    Crépin, Delphine; Benomar, Yacir; Riffault, Laure; Amine, Hamza; Gertler, Arieh; Taouis, Mohammed

    2014-03-25

    Early in life, leptin plays a crucial role in hypothalamic neural organization. Leptin, most likely, controls neural gene expression conferring then specific phenotype regarding energy homeostasis. MicroRNAs are new regulators for several physiological functions, including the regulation of metabolism. However, the impact of leptin on hypothalamic microRNA patterns remains unknown. Here, we demonstrate that miR-200a, miR-200b and miR-429 are up-regulated in the hypothalamus of genetically obese and leptin deficient ob/ob mice. Leptin treatment down-regulates these miRNAs in ob/ob hypothalamus. The hypothalamic silencing of miR-200a increased the expression level of leptin receptor and insulin receptor substrate 2, reduced body weight gain, and restored liver insulin responsiveness. In addition, the overexpression of pre-miR-200a in a human neuroblastoma cell line impaired insulin and leptin signaling. These findings link the alteration of leptin and insulin signaling to the up-regulation of hypothalamic miR-200a which could be a new target for treatment of obesity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Serum leptin levels in children and adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index

    DEFF Research Database (Denmark)

    Kiess, W; Anil, M; Blum, W F

    1998-01-01

    The ob protein, termed leptin, is produced by adipocytes and is thought to act as an afferent satiety signal regulating weight through suppressing appetite and stimulating energy expenditure in humans and/or rodents. Insulin has been found to be a potent stimulator of leptin expression in rodents...

  4. Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

    DEFF Research Database (Denmark)

    Wewer Albrechtsen, Nicolai J.; Kuhre, Rune E.; Hornburg, Daniel

    2017-01-01

    that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in...

  5. Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Rasidakis Antonis

    2009-04-01

    Full Text Available Abstract Background Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α. Insulin-like growth factor I (IGF-I mediates the metabolic effects of growth hormone (GH. The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD. The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I levels and furthermore, whether these changes are related to systemic inflammation. Methods We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β, interleukin 6 (IL-6 and interleukin 8 (IL-8 levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1 and two weeks later (Day 15. 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema. Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA. Results Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p Conclusion Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.

  6. The fluctuation of blood glucose, insulin and glucagon concentrations before and after insulin therapy in type 1 diabetes

    Science.gov (United States)

    Arif, Idam; Nasir, Zulfa

    2015-09-01

    A dynamical-systems model of plasma glucose, insulin and glucagon concentrations has been developed to investigate the effects of insulin therapy on blood glucose, insulin and glucagon regulations in type 1 diabetic patients. Simulation results show that the normal regulation of blood glucose concentration depends on insulin and glucagon concentrations. On type 1 diabetic case, the role of insulin on regulating blood glucose is not optimal because of the destruction of β cells in pancreas. These β cells destructions cause hyperglycemic episode affecting the whole body metabolism. To get over this, type 1 diabetic patients need insulin therapy to control the blood glucose level. This research has been done by using rapid acting insulin (lispro), long-acting insulin (glargine) and the combination between them to know the effects of insulin therapy on blood glucose, insulin and glucagon concentrations. Simulation results show that these different types of insulin have different effects on blood glucose concentration. Insulin therapy using lispro shows better blood glucose control after consumption of meals. Glargin gives better blood glucose control between meals and during sleep. Combination between lispro and glargine shows better glycemic control for whole day blood glucose level.

  7. Trajectories of BMI change impact glucose and insulin metabolism.

    Science.gov (United States)

    Walsh, E I; Shaw, J; Cherbuin, N

    2018-03-01

    The aim of this study was to examine, in a community setting, whether trajectory of weight change over twelve years is associated with glucose and insulin metabolism at twelve years. Participants were 532 community-living middle-aged and elderly adults from the Personality and Total Health (PATH) Through Life study. They spanned the full weight range (underweight/normal/overweight/obese). Latent class analysis and multivariate generalised linear models were used to investigate the association of Body Mass Index (BMI, kg/m 2 ) trajectory over twelve years with plasma insulin (μlU/ml), plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at follow-up. All models were adjusted for age, gender, hypertension, pre-clinical diabetes status (normal fasting glucose or impaired fasting glucose) and physical activity. Four weight trajectories were extracted; constant normal (mean baseline BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI, individuals in the constant high and increase trajectories had significantly higher plasma insulin, greater insulin resistance, and higher beta cell function than those in the constant normal trajectory. Individuals in the decrease trajectory did not differ from the constant normal trajectory. Current BMI significantly interacted with preceding BMI trajectory in its association with plasma insulin, insulin resistance, and beta cell function. The trajectory of preceding weight has an independent effect on blood glucose metabolism beyond body weight measured at any given point in time. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier

  8. Mathematical model of glucose-insulin homeostasis in healthy rats.

    Science.gov (United States)

    Lombarte, Mercedes; Lupo, Maela; Campetelli, German; Basualdo, Marta; Rigalli, Alfredo

    2013-10-01

    According to the World Health Organization there are over 220 million people in the world with diabetes and 3.4 million people died in 2004 as a consequence of this pathology. Development of an artificial pancreas would allow to restore control of blood glucose by coupling an infusion pump to a continuous glucose sensor in the blood. The design of such a device requires the development and application of mathematical models which represent the gluco-regulatory system. Models developed by other research groups describe very well the gluco-regulatory system but have a large number of mathematical equations and require complex methodologies for the estimation of its parameters. In this work we propose a mathematical model to study the homeostasis of glucose and insulin in healthy rats. The proposed model consists of three differential equations and 8 parameters that describe the variation of: blood glucose concentration, blood insulin concentration and amount of glucose in the intestine. All parameters were obtained by setting functions to the values of glucose and insulin in blood obtained after oral glucose administration. In vivo and in silico validations were performed. Additionally, a qualitative analysis has been done to verify the aforementioned model. We have shown that this model has a single, biologically consistent equilibrium point. This model is a first step in the development of a mathematical model for the type I diabetic rat. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Grain sorghum muffin reduces glucose and insulin responses in men.

    Science.gov (United States)

    Poquette, Nicole M; Gu, Xuan; Lee, Sun-Ok

    2014-05-01

    Diabetes and obesity have sparked interest in identifying healthy, dietary carbohydrates as functional ingredients for controlling blood glucose and insulin levels. Grain sorghum has been known to be a slowly digestible cereal; however, research is limited on its health effects in humans. The objectives of this study were to measure the contents of functional starch fractions, SDS (slowly-digestible starch) and RS (resistant starch), and to investigate the effects of grain sorghum on postprandial plasma glucose and insulin levels in 10 healthy men. A whole-wheat flour muffin (control) was compared with the grain sorghum muffin with both muffins containing 50 g of total starch. Using a randomized-crossover design, male subjects consumed treatments within a one-week washout period, and glucose and insulin levels were observed at 15 minutes before and 0, 15, 30, 45, 60, 75, 90, 120, 180 minutes after consumption. The mean glucose responses reduced after consuming grain sorghum, particularly at 45-120 minute intervals, and mean insulin responses reduced at 15-90 minute intervals compared to control (P < 0.05). The mean incremental area under the curve (iAUC) was significantly lowered for plasma glucose responses about an average of 35% from 3863 ± 443 to 2871 ± 163 mg (∼3 h) dL(-1) (P < 0.05). Insulin responses also reduced significantly from 3029 ± 965 μU (∼3 h) L(-1) for wheat to 1357 ± 204 with sorghum (P < 0.05). Results suggest that grain sorghum is a good functional ingredient to assist in managing glucose and insulin levels in healthy individuals.

  10. TRPM5 regulates glucose-stimulated insulin secretion

    OpenAIRE

    Brixel, Lili R.; Monteilh-Zoller, Mahealani K.; Ingenbrandt, Claudia S.; Fleig, Andrea; Penner, Reinhold; Enklaar, Thorsten; Zabel, Bernhard U.; Prawitt, Dirk

    2010-01-01

    Insulin secretion in β-pancreatic cells due to glucose stimulation requires the coordinated alteration of cellular ion concentrations and a substantial membrane depolarization to enable insulin vesicle fusion with the cellular membrane. The cornerstones of this cascade are well characterized, yet current knowledge argues for the involvement of additional ion channels in this process. TRPM5 is a cation channel expressed in β-cells and proposed to be involved in coupling intracellular Ca2+ rele...

  11. Comparison of the effects of endurance, resistance and concurrent training on insulin resistance and adiponectin-leptin ratio in diabetic rat

    OpenAIRE

    A. Saremi

    2017-01-01

    Background: The obesity-related hormones leptin and adiponectin are independently and oppositely associated with insulin resistance. Objective: The aim of the present study was to investigate the effect of endurance, resistance and concurrent training on insulin resistance and adiponectin-leptin ratio in diabetic rats. Methods: Ten out of 50 male Wistar rats were separated as healthy subjects. Then diabetes was induced in the remaining rats by the injection of streptozotocin. Diabetic r...

  12. Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation.

    Science.gov (United States)

    Frank, N; Hermida, P; Sanchez-Londoño, A; Singh, R; Gradil, C M; Uricchio, C K

    2017-07-01

    Octreotide is a somatostatin analog that suppresses insulin secretion. We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. Twelve horses, N = 5, ID = 7. Prospective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1.0 μg/kg IV) was then administered, and blood was collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 minute, and 2, 3, 4, 6, 8, 12, and 24 hour for measurement of glucose and insulin concentrations. Area under the curve (AUC) values were calculated. Mean AUC values for glucose and insulin did not differ between normal (n = 5) and ID (n = 7) groups after octreotide injection. Significant time (P insulin concentrations. A group × time interaction (P = .091) was detected for insulin concentrations after administration of octreotide, but the group (P = .33) effect was not significant. Octreotide suppresses insulin secretion, resulting in hyperglycemia, and then concentrations increase above baseline as glycemic control is restored. Our hypothesis that octreotide causes insulin concentrations to decrease in horses was supported, but differences between N and ID groups did not reach statistical significance when blood glucose and insulin responses were compared. The utility of an octreotide response test remains to be determined. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  13. Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

  14. Non inflammatory boronate based glucose-responsive insulin delivery systems.

    Directory of Open Access Journals (Sweden)

    Indrani Dasgupta

    Full Text Available Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT. This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA, a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L-40 mmoles/L. The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger.

  15. Insulin and non-insulin mediated vasodilation and glucose uptake in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Scheede-Bergdahl, Celena; Olsen, David Benee; Reving, Danny

    2009-01-01

    AIMS: The objective was to re-examine endothelial function, insulin mediated vasodilation and glucose extraction in the forearm of patients with type 2 diabetes (T2DM) and matched control subjects (CON) to investigate whether blood flow impairments result from diabetes per se or from concurrent...... disease. METHODS: 18 subjects (10 with T2DM, 8 CON) had graded brachial artery infusions of endothelial dependent (acetylcholine: 15, 30, 60mug/min), endothelial independent (sodium nitroprusside: 1, 3, 10mug/min) and partially endothelial mediated (adenosine: 50, 150, 500mug/min) vasodilators...... forearm blood flow were similar in T2DM and CON. However, insulin mediated forearm blood flow responses and glucose extraction were lower in T2DM versus CON. CONCLUSION: The vasodilatory effect of insulin is impaired in T2DM although bulk flow capacity is maintained. Insulin mediated glucose extraction...

  16. Cocoa, glucose tolerance, and insulin signaling: cardiometabolic protection.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Mai, Francesca; Martella, Letizia; De Feo, Martina; Soddu, Daniele; Fellini, Emanuela; Veneri, Mariangela; Stamerra, Cosimo A; Ferri, Claudio

    2015-11-18

    Experimental and clinical evidence reported that some polyphenol-rich natural products may offer opportunities for the prevention and treatment of type 2 diabetes, due to their biological properties. Natural products have been suggested to modulate carbohydrate metabolism by various mechanisms, such as restoring β-cell integrity and physiology and enhancing insulin-releasing activity and glucose uptake. Endothelium is fundamental in regulating arterial function, whereas insulin resistance plays a pivotal role in pathophysiological mechanisms of prediabetic and diabetic states. Glucose and insulin actions in the skeletal muscle are improved by insulin-dependent production of nitric oxide, favoring capillary recruitment, vasodilatation, and increased blood flow. Endothelial dysfunction, with decreased nitric oxide bioavailability, is a critical step in the development of atherosclerosis. Furthermore, insulin resistance has been described, at least in part, to negatively affect endothelial function. Consistent with this, conditions of insulin resistance are usually linked to endothelial dysfunction, and the exposure of the endothelial cells to cardiovascular risk factors such as hypertension, dyslipidemia, and hyperglycemia is associated with reduced nitric oxide bioavailability, resulting in impaired endothelial-dependent vasodilatation. Moreover, endothelial dysfunction has been described as an independent predictor of cardiovascular risk and events. Cocoa and cocoa flavonoids may positively affect the pathophysiological mechanisms involved in insulin resistance and endothelial dysfunction with possible benefits in the prevention of cardiometabolic diseases.

  17. Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul

    2003-01-01

    We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp...... Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux......, glucose storage, and glucose production were unchanged. Insulin secretion rates increased in response to Intralipid infusion, but disposition indices (DI = insulin action.insulin secretion) were unchanged. In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in the oxidative (but...

  18. Insulin regulation of renal glucose metabolism in conscious dogs.

    Science.gov (United States)

    Cersosimo, E; Judd, R L; Miles, J M

    1994-01-01

    Previous studies indicating that postabsorptive renal glucose production is negligible used the net balance technique, which cannot partition simultaneous renal glucose production and glucose uptake. 10 d after surgical placement of sampling catheters in the left renal vein and femoral artery and a nonobstructive infusion catheter in the left renal artery of dogs, systemic and renal glucose and glycerol kinetics were measured with peripheral infusions of [3-3H]glucose and [2-14C]glycerol. After baseline measurements, animals received a 2-h intrarenal infusion of either insulin (n = 6) or saline (n = 6). Left renal vein insulin concentration increased from 41 +/- 8 to 92 +/- 23 pmol/l (P gluconeogenesis from glycerol decreased from 0.23 +/- 0.06 to 0.17 +/- 0.04 mumol.kg-1.min-1 (P dogs. Physiological hyperinsulinemia suppresses renal glucose production and stimulates renal glucose uptake by approximately 75%. We conclude that the kidney makes a major contribution to systemic glucose metabolism in the postabsorptive state. PMID:8200996

  19. The Effect of Long Term Starvation on Galanin, Leptin, Thyroid Hormones, Insulin, Prolactin, Growth Hormone, Ghrelin and Factors Involved in Energy Metabolism in Adult Goats

    Directory of Open Access Journals (Sweden)

    Neda ESKANDARZADE

    2015-07-01

    Full Text Available Some hormonal disturbances have been demonstrated in starvation, but in ruminants such as goats, the role of galanin in adaptation to starvation or endocrine functions is not well studied. The present study was conducted to assess the effect of long term starvation on galanin, leptin, thyroid hormones, insulin, prolactin, growth hormone, ghrelin and factors involved in energy metabolism including HDL, Cholesterol, β-hydroxybutyrate, glucose, NEFA, TG and VLDL concentrations in adult goats. Eight non-lactating non-pregnant goats aged 4-5 years and BCS 3 were randomly divided to control and test groups. The animals were trained to eat their daily forage ration during a 10 day period. The experimental procedure was applied for 20 days, during which control group received 120% of maintenance energy, while the test group was supplied with 80% of maintenance energy for the first 10 days and with 40% of maintenance energy for another 10 days. Blood samples were collected at day 10 of training and 2, 4, 10, 12, 14 and 20 days after beginning of starvation. Blood parameters were measured according to standard procedures. No significant difference was observed in the concentrations of cholesterol, fT3, T4, T3, growth hormone, NEFA, insulin and ghrelin between control and test groups (P=0.05. There was significant difference in galanin, leptin, fT4, HDL, glucose, TG, VLDL and prolactin concentrations between control and test groups (P=0.05. Control of energy balance and the role of galanin in adaptation to long starvation or endocrine functions in goat are different from other species.

  20. Ingestion of Carbohydrate-Rich Supplements during Gestation Programs Insulin and Leptin Resistance but not Body Weight Gain in Adult Rat Offspring.

    Science.gov (United States)

    Beck, Bernard; Richy, Sébastien; Archer, Zoe A; Mercer, Julian G

    2012-01-01

    Prenatal nutritional conditions can predispose to development of obesity and metabolic syndrome in adulthood. Gestation with its important modifications in hormonal status is a period of changes in normal feeding habits with pulses of consumption or avoidance of certain categories of food. We tried to mimic in an animal model some changes in food consumption patterns observed in pregnant women. For this purpose, Long-Evans female rats were fed during the dark period, their usual pre-gestational food quantity, and were allowed to complete their daily intake with either a restricted control (Cr), high-fat (HF), or high-carbohydrate (HC) diet available ad libitum during the light period. Dams fed a control diet ad libitum (Ca) served as controls. Body weight and composition, food intake, and metabolic hormones (insulin, leptin) were recorded in male offspring until 20 weeks after birth. Cr and HC females ate less than Ca females (-16%; p weight deficit from birth until 6 (HC group) and 10 (Cr group) weeks of age (p body weight in Cr offspring, but was increased in HC offspring that in addition, had increased plasma insulin, blood glucose, and subcutaneous adipose tissue mass. HF dams ate more than Ca dams (+13%; p supplement ingestion during gestation therefore leads to insulin and leptin resistance in adult offspring independently of lower birth weight. These hormonal changes characterize obesity-prone animals. We therefore suggest that attention should be paid to the carbohydrate snacking and overall carbohydrate content in the diet during the last weeks (or months) preceding delivery to limit development of later metabolic disorders in offspring.

  1. Alterations in human milk leptin and insulin are associated with early changes in the infant intestinal microbiome.

    Science.gov (United States)

    Lemas, Dominick J; Young, Bridget E; Baker, Peter R; Tomczik, Angela C; Soderborg, Taylor K; Hernandez, Teri L; de la Houssaye, Becky A; Robertson, Charles E; Rudolph, Michael C; Ir, Diana; Patinkin, Zachary W; Krebs, Nancy F; Santorico, Stephanie A; Weir, Tiffany; Barbour, Linda A; Frank, Daniel N; Friedman, Jacob E

    2016-05-01

    Increased maternal body mass index (BMI) is a robust risk factor for later pediatric obesity. Accumulating evidence suggests that human milk (HM) may attenuate the transfer of obesity from mother to offspring, potentially through its effects on early development of the infant microbiome. Our objective was to identify early differences in intestinal microbiota in a cohort of breastfeeding infants born to obese compared with normal-weight (NW) mothers. We also investigated relations between HM hormones (leptin and insulin) and both the taxonomic and functional potentials of the infant microbiome. Clinical data and infant stool and fasting HM samples were collected from 18 NW [prepregnancy BMI (in kg/m(2)) 30.0) mothers and their exclusively breastfed infants at 2 wk postpartum. Infant body composition at 2 wk was determined by air-displacement plethysmography. Infant gastrointestinal microbes were estimated by using 16S amplicon and whole-genome sequencing. HM insulin and leptin were determined by ELISA; short-chain fatty acids (SCFAs) were measured in stool samples by using gas chromatography. Power was set at 80%. Infants born to obese mothers were exposed to 2-fold higher HM insulin and leptin concentrations (P < 0.01) and showed a significant reduction in the early pioneering bacteria Gammaproteobacteria (P = 0.03) and exhibited a trend for elevated total SCFA content (P < 0.06). Independent of maternal prepregnancy BMI, HM insulin was positively associated with both microbial taxonomic diversity (P = 0.03) and Gammaproteobacteria (e.g., Enterobacteriaceae; P = 0.04) and was negatively associated with Lactobacillales (e.g., Streptococcaceae; P = 0.05). Metagenomic analysis showed that HM leptin and insulin were associated with decreased bacterial proteases, which are implicated in intestinal permeability, and reduced concentrations of pyruvate kinase, a biomarker of pediatric gastrointestinal inflammation. Our results indicate that, although maternal obesity may

  2. Alterations in human milk leptin and insulin are associated with early changes in the infant intestinal microbiome12

    Science.gov (United States)

    Lemas, Dominick J; Young, Bridget E; Baker, Peter R; Tomczik, Angela C; Soderborg, Taylor K; Hernandez, Teri L; de la Houssaye, Becky A; Robertson, Charles E; Rudolph, Michael C; Ir, Diana; Patinkin, Zachary W; Krebs, Nancy F; Santorico, Stephanie A; Weir, Tiffany; Barbour, Linda A; Frank, Daniel N; Friedman, Jacob E

    2016-01-01

    Background: Increased maternal body mass index (BMI) is a robust risk factor for later pediatric obesity. Accumulating evidence suggests that human milk (HM) may attenuate the transfer of obesity from mother to offspring, potentially through its effects on early development of the infant microbiome. Objectives: Our objective was to identify early differences in intestinal microbiota in a cohort of breastfeeding infants born to obese compared with normal-weight (NW) mothers. We also investigated relations between HM hormones (leptin and insulin) and both the taxonomic and functional potentials of the infant microbiome. Design: Clinical data and infant stool and fasting HM samples were collected from 18 NW [prepregnancy BMI (in kg/m2) 30.0) mothers and their exclusively breastfed infants at 2 wk postpartum. Infant body composition at 2 wk was determined by air-displacement plethysmography. Infant gastrointestinal microbes were estimated by using 16S amplicon and whole-genome sequencing. HM insulin and leptin were determined by ELISA; short-chain fatty acids (SCFAs) were measured in stool samples by using gas chromatography. Power was set at 80%. Results: Infants born to obese mothers were exposed to 2-fold higher HM insulin and leptin concentrations (P < 0.01) and showed a significant reduction in the early pioneering bacteria Gammaproteobacteria (P = 0.03) and exhibited a trend for elevated total SCFA content (P < 0.06). Independent of maternal prepregnancy BMI, HM insulin was positively associated with both microbial taxonomic diversity (P = 0.03) and Gammaproteobacteria (e.g., Enterobacteriaceae; P = 0.04) and was negatively associated with Lactobacillales (e.g., Streptococcaceae; P = 0.05). Metagenomic analysis showed that HM leptin and insulin were associated with decreased bacterial proteases, which are implicated in intestinal permeability, and reduced concentrations of pyruvate kinase, a biomarker of pediatric gastrointestinal inflammation. Conclusion: Our

  3. Benefits of leptin therapy in HIV patients

    Directory of Open Access Journals (Sweden)

    Uma Sinha

    2012-01-01

    Full Text Available Leptin therapy in human recombinant form has recently been used in HIV-associated lipodystrophy syndrome on experimental basis in some small short-term clinical trials. It has shown its beneficial effects only in hypoleptinemic HIV-infected patients by causing definite improvement in their insulin sensitivity, glucose tolerance, lipid status, and truncal obesity. Leptin prevents lipotoxicity and activates insulin signaling pathways through several postulated mechanisms. Central leptin insufficiency with peripheral hyperleptinemia has come out to be a significant contributor to the development of obesity and metabolic syndrome. In this article, we will review the basis of leptin therapy in HIV patients, with its promises. However, further larger clinical trials are needed to prove its long-term efficacy in the control of metabolic complications related to HIV therapy.

  4. Modulation of leptin, insulin, and growth hormone in obese pony mares under chronic nutritional restriction and supplementation with ractopamine hydrochloride.

    Science.gov (United States)

    Buff, Preston R; Johnson, Philip J; Wiedmeyer, Charles E; Ganjam, Venkataseshu K; Messer Iv, Nat T; Keisler, Duane H

    2006-01-01

    Horses fed beyond their nutritional requirement and that are physically inactive will develop obesity, which is often accompanied by insulin resistance and heightened risk of laminitis. The use of pharmacologic agents in combination with nutritional restriction may promote weight loss in obese horses unable to exercise because of laminitic pain. This study shows that reducing feed intake of brome grass hay to 75% of ad libitum intake in obese pony mares reduces body weight without induced exercise. Additional supplementation of ractopamine hydrochloride for 6 weeks resulted in a tendency for increased weight loss. Subsequent modulation of obesity-associated hormones, leptin and insulin, as a result of caloric restriction was observed.

  5. Refractory hyperglycaemia induced by glucose-insulin-potassium infusion in acute myocardial infarction

    NARCIS (Netherlands)

    Svilaas, Tone; van der Horst, I.C.C.; Nijsten, M.W.N.; Zijlstra, F.

    2006-01-01

    Background. Recent randomised clinical trials have not confirmed the beneficial effects of glucose-insulin-potassium (GIK) infusion observed in experimental models of myocardial ischaemia and infarction. Methods. We investigated glucose levels and insulin dose in 107 patients treated with

  6. Sunitinib specifically augments glucose-induced insulin secretion.

    Science.gov (United States)

    Lutz, Stefan Z; Ullrich, Axel; Häring, Hans-Ulrich; Ullrich, Susanne; Gerst, Felicia

    2017-08-01

    The tyrosine kinase inhibitor sunitinib is used for the treatment of numerous cancers in humans. In diabetic patients, sunitinib lowers blood glucose levels and improves glycaemic control. This study aims to analyse whether sunitinib has specific and direct effects on insulin secreting β-cells. Regulation of insulin secretion, of cellular cAMP levels and activation of signalling pathways were examined upon exposure of rat insulinoma INS-1E cells to sunitinib under specific stimulatory and inhibitory conditions. Secreted insulin and cellular cAMP levels were measured using RIA and ELISA, respectively. Protein phosphorylations were examined on western blots. Sunitinib enhanced glucose-induced insulin secretion (GIIS) concentration-dependently, reaching a maximal stimulation at 2μM. Sunitinib further augmented insulin secretion in the presence of elevated cAMP levels and the FFAR1 agonists. Adrenaline and the PKA inhibitor H89 counteracted the stimulatory effect of sunitinib on secretion. However, sunitinib altered neither the cellular levels of cAMP nor the phosphorylation of PKA. Sunitinib did not reduce IGF-1-induced phosphorylation of AKT/PKB and ERK1/2. In conclusion, these results suggest that sunitinib stimulates GIIS by a direct effect on β-cells, which may contribute to the glucose-lowering action of the tyrosine kinase inhibitor in humans. Copyright © 2017. Published by Elsevier Inc.

  7. Insulin receptor and glucose transporter-4 expression in the skeletal ...

    African Journals Online (AJOL)

    Background: Stress defined as a disruption in the normal homeostatic functions of an organism caused by stressor (a physiological or psychological challenge) is ... Conclusion: Chronic stress evokes insulin insensitivity and impairs glucose metabolism through the down-regulation of INSR and GLUT4 in skeletal muscles.

  8. Bayesian model discrimination for glucose-insulin homeostasis

    DEFF Research Database (Denmark)

    Andersen, Kim Emil; Brooks, Stephen P.; Højbjerre, Malene

    In this paper we analyse a set of experimental data on a number of healthy and diabetic patients and discuss a variety of models for describing the physiological processes involved in glucose absorption and insulin secretion within the human body. We adopt a Bayesian approach which facilitates th...

  9. Glucose control: Non-insulin therapies | Office | South African Family ...

    African Journals Online (AJOL)

    South African Family Practice. Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 56, No 1 (2014) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Glucose control: Non-insulin therapies. Editorial Office. Abstract. No Abstract.

  10. Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Merida (Venezuela).

    Science.gov (United States)

    Uzcátegui, Euderruh; Valery, Lenin; Uzcátegui, Lilia; Gómez Pérez, Roald; Marquina, David; Baptista, Trino

    2015-06-01

    The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged > or =18 years from the Libertador district in Merida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients' self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

  11. Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells

    International Nuclear Information System (INIS)

    Meerson, Ari; Yehuda, Hila

    2016-01-01

    Obesity is a risk factor for colorectal cancer (CRC). Normal and tumor cells respond to metabolic hormones, such as leptin and insulin. Thus, obesity-associated resistance to these hormones likely leads to changes in gene expression and behavior of tumor cells. However, the mechanisms affected by leptin and insulin signaling in CRC cells remain mostly unknown. We hypothesized that microRNAs (miRNAs) are involved in the regulation of tumorigenesis-related gene expression in CRC cells by leptin and insulin. To test this hypothesis, miRNA levels in the CRC-derived cell lines HCT-116, HT-29 and DLD-1 were profiled, following leptin and insulin treatment. Candidate miRNAs were validated by RT-qPCR. Predicted miRNA targets with known roles in cancer, were validated by immunoblots and reporter assays in HCT-116 cells. Transfection of HCT-116 cells with candidate miRNA mimic was used to test in vitro effects on proliferation and invasion. Of ~800 miRNAs profiled, miR-4443 was consistently up-regulated by leptin and insulin in HCT-116 and HT-29, but not in DLD-1, which lacked normal leptin receptor expression. Dose response experiments showed that leptin at 100 ng/ml consistently up-regulated miR-4443 in HCT-116 cells, concomitantly with a significant decrease in cell invasion ability. Transfection with miR-4443 mimic decreased invasion and proliferation of HCT-116 cells. Moreover, leptin and miR-4443 transfection significantly down-regulated endogenous NCOA1 and TRAF4, both predicted targets of miR-4443 with known roles in cancer metastasis. miR-4443 was found to directly regulate TRAF4 and NCOA1, as validated by a reporter assay. The up-regulation of miR-4443 by leptin or insulin was attenuated by the inhibition of MEK1/2. Our findings suggest that miR-4443 acts in a tumor-suppressive manner by down-regulating TRAF4 and NCOA1 downstream of MEK-C/EBP-mediated leptin and insulin signaling, and that insulin and/or leptin resistance (e.g. in obesity) may suppress this pathway

  12. Persistent inflammation and its relationship to leptin and insulin in phases of bipolar disorder from acute depression to full remission.

    Science.gov (United States)

    Tsai, Shang-Ying; Chung, Kuo-Hsuan; Huang, Shou-Hung; Chen, Pao-Huan; Lee, Hsin-Chien; Kuo, Chian-Jue

    2014-12-01

    A proinflammatory phase with various immunomodulatory mechanisms has been noted in bipolar mania and major depression. Weight gain and increased production of leptin may be associated with immunomodulation and insulin resistance in bipolar disorder. However, immunomodulation and its linkage with leptin and insulin in the depressive episode of bipolar disorder remain unclear. We investigated alterations in inflammatory markers and their relationship with leptin and insulin levels in patients with phases of bipolar disorder from acute depression to full remission. Thirty-two physically healthy bipolar I depressed patients aged insulin, high-sensitivity C-reactive protein (hs-CRP), soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 1 (sTNF-R1), and interleukin-1 receptor antagonist (IL-1Ra) in three phases, i.e., acute depression, subsequent partial remission, and full remission. In acute depression, subsequent partial remission, and full remission, patients with bipolar disorder had significantly higher mean levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R compared with control subjects. The IL-1Ra and sTNF-R1 levels in various affective phases were significantly correlated to body mass index, leptin level, circulating lipids, and medication status. The sIL-2R levels in the three affective phases were all independent of other inflammatory markers and clinical and laboratory variables. Patients showed no alteration of sIL-6R levels through the depressive episode. Patients with bipolar disorder in depressive episodes may exhibit persistent inflammation with elevated levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R but not sIL-6R from the acute phases to full remission. Only sIL-2R production seems to be tightly linked with the pathophysiology of bipolar depression and is independent of insulin and leptin levels. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity a

    OpenAIRE

    Pedroso, João A.B.; Buonfiglio, Daniella C.; Cardinali, Lais I.; Furigo, Isadora C.; Ramos-Lobo, Angela M.; Tirapegui, Julio; Elias, Carol F.; Donato, Jose

    2014-01-01

    Therapies that improve leptin sensitivity have potential as an alternative treatment approach against obesity and related comorbidities. We investigated the effects of Socs3 gene ablation in different mouse models to understand the role of SOCS3 in the regulation of leptin sensitivity, diet-induced obesity (DIO) and glucose homeostasis. Neuronal deletion of SOCS3 partially prevented DIO and improved glucose homeostasis. Inactivation of SOCS3 only in LepR-expressing cells protected against lep...

  14. Prediction of clamp-derived insulin sensitivity from the oral glucose insulin sensitivity index

    DEFF Research Database (Denmark)

    Tura, Andrea; Chemello, Gaetano; Szendroedi, Julia

    2018-01-01

    that underwent both a clamp and an OGTT or meal test, thereby allowing calculation of both the M value and OGIS. The population was divided into a training and a validation cohort (n = 359 and n = 154, respectively). After a stepwise selection approach, the best model for M value prediction was applied......AIMS/HYPOTHESIS: The euglycaemic-hyperinsulinaemic clamp is the gold-standard method for measuring insulin sensitivity, but is less suitable for large clinical trials. Thus, several indices have been developed for evaluating insulin sensitivity from the oral glucose tolerance test (OGTT). However......, most of them yield values different from those obtained by the clamp method. The aim of this study was to develop a new index to predict clamp-derived insulin sensitivity (M value) from the OGTT-derived oral glucose insulin sensitivity index (OGIS). METHODS: We analysed datasets of people...

  15. Evaluation of glucose response to 3 types of insulin using a continuous glucose monitoring system in healthy alpacas.

    Science.gov (United States)

    Byers, S R; Beemer, O M; Lear, A S; Callan, R J

    2014-01-01

    Persistent hyperglycemia is common in alpacas and typically requires insulin administration for resolution; however, little is known about alpacas' response to different insulin formulations. To evaluate the effects of 3 insulin formulations on blood glucose concentrations and the use of a continuous glucose monitoring (CGM) system in alpacas. Six healthy alpacas. The CGM was installed in the left paralumbar fossa at the start of this crossover study and recorded data every 5 minutes. Regular insulin, NPH insulin, insulin glargine, and dextrose were administered to each alpaca over a 2-week period. Blood samples were collected for glucose testing at 0, 1, 2, 4, 6, 8, and 12 hours, and then every 6 hours after each administration of insulin or dextrose. Data were compared by using method comparison techniques, error grid plots, and ANOVA. Blood glucose concentrations decreased most rapidly after regular insulin administration when administered IV or SC as compared to the other formulations. The NPH insulin produced the longest suppression of blood glucose. The mean CGM interstitial compartment glucose concentrations were typically lower than the intravascular compartment glucose concentrations. The alpacas had no adverse reactions to the different insulin formulations. The NPH insulin might be more appropriate for long-term use in hyperglycemic alpacas because of its extended duration of action. A CGM is useful in monitoring glucose trends and reducing blood collection events, but it should not be the sole method for determining treatment protocols. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  16. Glucose- and temperature-sensitive nanoparticles for insulin delivery

    Directory of Open Access Journals (Sweden)

    Wu JZ

    2017-05-01

    Full Text Available Jun-Zi Wu,1 Gareth R Williams,2 He-Yu Li,1 Dongxiu Wang,3 Huanling Wu,1 Shu-De Li,4 Li-Min Zhu1 1College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 2UCL School of Pharmacy, University College London, London, UK; 3Central Laboratory, Environmental Monitoring Center of Kunming, 4School of Basic Medical Sciences, Kunming Medical University, Kunming, People’s Republic of China Abstract: Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid-b-diethylene glycol methyl ether methacrylate; p(AAPBA-b-DEGMA were prepared by reversible addition–fragmentation chain transfer polymerization. Successful polymerization was evidenced by 1H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC. The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C–47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs, and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA-b-DEGMA NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they

  17. [Assay of adiponectin, leptin, true insulin and ghrelin levels in preterm human milk, and its relationship with infants growth].

    Science.gov (United States)

    Han, Luyan; Li, Ming; Yu, Xinting; Sun, Xiujing; Wang, Danhua

    2014-07-01

    To understand adiponectin, leptin, insulin and ghrelin levels in preterm colostrum and mature milk and their influence on the growth and development of the premature infant. The study subjects were divided into two groups: preterm group and control group. Specimens of colostrum and mature milk on 42nd day after delivery were collected, the general situation of maternal and infants growth parameters at birth and at postnatal 42 days were recorded. Leptin, adiponectin, insulin and ghrelin levels in colustrum and mature milk were determined and compared. A total of 128 mother-infant pairs were involved. There were 128 specimens of colostrums (80 from preterm group, 48 from control group) and 94 specimens of mature milk(50 from premature group, 44 from control group). The levels of colostrum, mature milk adiponectin, leptin, and insulin were not significantly different between the 2 groups; ghrelin levels in colostrum and mature milk of premature group were significantly lower than those in control group (P = 0.038), adiponectin and leptin levels in colostrum were higher than those of the mature milk (P milk (P 34 weeks group). True insulin level of mature milk in 34 weeks group was higher than that of > 34 weeks group (29.3 vs. 21.6 mU/L, P = 0.045); true insulin level in colostrums in ≤ 34 weeks group was lower than that in mature milk (21.7 vs. 29.3 mU/L, P = 0.000). Adiponectin levels in colostrum and 42 days weight gain were negatively correlated (r = -0.362, P = 0.025) . Insulin level in mature milk had a negative correlation with birth weight (r = -0.319, P = 0.029) . Ghrelin levels in colostrum and birth weight, length, head circumference, head circumference on 42(nd) day were positively correlated (r = 0.271,0.261,0.360, P hormones in milk might participate in the regulation of suitable growth after birth. Premature birth affects hormone levels in breast milk. Breast feeding is very important in preterm infants.

  18. Impaired insulin-stimulated nonoxidative glucose metabolism in glucose-tolerant women with previous gestational diabetes

    DEFF Research Database (Denmark)

    Damm, P; Vestergaard, H; Kühl, C

    1996-01-01

    euglycemic clamp including indirect calorimetry. All women were lean and had normal oral glucose tolerance test results. Activities of glycogen synthase, phosphofructokinase, and hexokinase were measured in vastus lateralis muscle biopsy specimens obtained in the basal state and after insulin stimulation....... RESULTS: Women with previous gestational diabetes had a decreased glucose disposal rate (pmetabolism (6.63 +/- 0.47 vs 9.04 +/- 0.57 mg/kg fat-free mass per minute, p

  19. [Relationship between leptin and body mass and metabolic syndrome in an adult population].

    Science.gov (United States)

    Martins, Maria do Carmo; Lima Faleiro, Luís; Fonseca, Aidil

    2012-11-01

    To analyze the relationship between leptin and obesity expressed as body mass index (BMI) and certain components of the metabolic syndrome (MS) in an adult population. The study included 103 subjects, 42 men and 61 women, aged over 30 years, clinically defined as non-diabetic but with personal or family history of cardiovascular disease. All subjects underwent fasting blood measurements of leptin, insulin, glucose, glucose after ingestion of 75g glucose, HDL cholesterol and triglycerides, and insulin resistance (IR) and BMI were calculated. BMI as an index of overall adiposity was strongly associated with serum leptin. BMI rose as serum leptin levels increased from the first to the third tertile; the correlation between leptin and BMI was strong, r=0.524 in men and r=0.603 in women, with high statistical significance (pcorrelations between leptin and IR, and leptin and insulinemia, were strong in both sexes. With regard to MS components, increased serum levels of the study variables were observed as leptin concentrations rose from the first to the third tertile (with the exception of HDL cholesterol, which decreased). Elevated serum leptin, particularly in obese individuals, should be taken as a warning sign of energy imbalance, poor diet, hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are strongly associated with cardiovascular disease and type 2 diabetes. Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  20. Detection of leptin in serum from patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Chu Yongli; Sun Yongyu; Qiu Hongyu

    2002-01-01

    Objective: To investigate the relationship between leptin and insulin resistance in polycystic ovary syndrome (PCOS). Methods: Blood samples for leptin, LH/FSH, fasting insulin and glucose measurement from 17 patients with PCOS and 20 cases as control group were analyzed by radioimmunoassay or oxidase test. Results: It showed that leptin, LH/FSH levels of serum, insulin resistant index (IRI) and body mass index (BMI) in patients with PCOS were significantly higher than that in the control group (P<0.05). Leptin level was positively related with IRI and LH/FSH and BMI (P<0.01, P<0.05, P<0.01). Conclusion: It was suspected that leptin accelerate insulin resistance, the interaction of two factors aggravate the change of pathophysiology in PCOS

  1. Estimation of umbilical cord blood leptin and insulin based on anthropometric data by means of artificial neural network approach: identifying key maternal and neonatal factors.

    Science.gov (United States)

    Guzmán-Bárcenas, José; Hernández, José Alfredo; Arias-Martínez, Joel; Baptista-González, Héctor; Ceballos-Reyes, Guillermo; Irles, Claudine

    2016-07-21

    Leptin and insulin levels are key factors regulating fetal and neonatal energy homeostasis, development and growth. Both biomarkers are used as predictors of weight gain and obesity during infancy. There are currently no prediction algorithms for cord blood (UCB) hormone levels using Artificial Neural Networks (ANN) that have been directly trained with anthropometric maternal and neonatal data, from neonates exposed to distinct metabolic environments during pregnancy (obese with or without gestational diabetes mellitus or lean women). The aims were: 1) to develop ANN models that simulate leptin and insulin concentrations in UCB based on maternal and neonatal data (ANN perinatal model) or from only maternal data during early gestation (ANN prenatal model); 2) To evaluate the biological relevance of each parameter (maternal and neonatal anthropometric variables). We collected maternal and neonatal anthropometric data (n = 49) in normoglycemic healthy lean, obese or obese with gestational diabetes mellitus women, as well as determined UCB leptin and insulin concentrations by ELISA. The ANN perinatal model consisted of an input layer of 12 variables (maternal and neonatal anthropometric and biochemical data from early gestation and at term) while the ANN prenatal model used only 6 variables (maternal anthropometric from early gestation) in the input layer. For both networks, the output layer contained 1 variable to UCB leptin or to UCB insulin concentration. The best architectures for the ANN perinatal models estimating leptin and insulin were 12-5-1 while for the ANN prenatal models, 6-5-1 and 6-4-1 were found for leptin and insulin, respectively. ANN models presented an excellent agreement between experimental and simulated values. Interestingly, the use of only prenatal maternal anthropometric data was sufficient to estimate UCB leptin and insulin values. Maternal BMI, weight and age as well as neonatal birth were the most influential parameters for leptin while

  2. Mitochondrial GTP Regulates Glucose-Induced Insulin Secretion

    OpenAIRE

    Kibbey, Richard G.; Pongratz, Rebecca L.; Romanelli, Anthony J.; Wollheim, Claes B.; Cline, Gary W.; Shulman, Gerald I.

    2007-01-01

    Substrate-level mitochondrial GTP (mtGTP) and ATP (mtATP) synthesis occurs by nucleotide-specific isoforms of the tricarboxylic acid (TCA) cycle enzyme succinyl CoA synthetase (SCS). Unlike mtATP, each molecule of glucose metabolized produces approximately one mtGTP in pancreatic β-cells independent of coupling with oxidative phosphorylation making mtGTP a potentially important fuel signal. siRNA suppression of the GTP-producing pathway (ΔSCS-GTP) reduced glucose-stimulated insulin secretion ...

  3. Astaxanthin prevents loss of insulin signaling and improves glucose metabolism in liver of insulin resistant mice.

    Science.gov (United States)

    Bhuvaneswari, Saravanan; Anuradha, Carani Venkatraman

    2012-11-01

    This study investigates the effects of astaxanthin (ASX) on insulin signaling and glucose metabolism in the liver of mice fed a high fat and high fructose diet (HFFD). Adult male Mus musculus mice of body mass 25-30 g were fed either normal chow or the HFFD. After 15 days, mice in each group were subdivided among 2 smaller groups and treated with ASX (2 mg·(kg body mass)⁻¹) in olive oil for 45 days. At the end of 60 days, HFFD-fed mice displayed insulin resistance while ASX-treated HFFD animals showed marked improvement in insulin sensitivity parameters. ASX treatment normalized the activities of hexokinase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase, and increased glycogen reserves in the liver. Liver tissue from ASX-treated HFFD-fed animals showed increased tyrosine phosphorylation and decreased serine phosphorylation of insulin receptor substrates (IRS)-1 and -2. ASX increased IRS 1/2 and phosphatidylinositol 3-kinase (PI3K) association and serine phosphorylation of Akt. In addition, ASX decreased HFFD-induced serine kinases (c-jun N-terminal kinase-1 and extracellular signal-regulated kinase-1). The results suggest that ASX treatment promotes the IRS-PI3K-Akt pathway of insulin signaling by decreasing serine phosphorylation of IRS proteins, and improves glucose metabolism by modulating metabolic enzymes.

  4. Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes?

    DEFF Research Database (Denmark)

    Staehr, P; Højlund, Kurt; Hother-Nielsen, O

    2003-01-01

    AIMS: In order to perform euglycaemic clamp studies in Type 2 diabetic patients, plasma glucose must be reduced to normal levels. This can be done either (i) acutely during the clamp study using high-dose insulin infusion, or (ii) slowly overnight preceding the clamp study using a low-dose insulin...... infusion. We assessed whether the choice of either of these methods to obtain euglycaemia biases subsequent assessment of glucose metabolism and insulin action. METHODS: We studied seven obese Type 2 diabetic patients twice: once with (+ ON) and once without (- ON) prior overnight insulin infusion. Glucose...... turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF). RESULTS: Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10...

  5. Prediction of clamp-derived insulin sensitivity from the oral glucose insulin sensitivity index.

    Science.gov (United States)

    Tura, Andrea; Chemello, Gaetano; Szendroedi, Julia; Göbl, Christian; Færch, Kristine; Vrbíková, Jana; Pacini, Giovanni; Ferrannini, Ele; Roden, Michael

    2018-05-01

    The euglycaemic-hyperinsulinaemic clamp is the gold-standard method for measuring insulin sensitivity, but is less suitable for large clinical trials. Thus, several indices have been developed for evaluating insulin sensitivity from the oral glucose tolerance test (OGTT). However, most of them yield values different from those obtained by the clamp method. The aim of this study was to develop a new index to predict clamp-derived insulin sensitivity (M value) from the OGTT-derived oral glucose insulin sensitivity index (OGIS). We analysed datasets of people that underwent both a clamp and an OGTT or meal test, thereby allowing calculation of both the M value and OGIS. The population was divided into a training and a validation cohort (n = 359 and n = 154, respectively). After a stepwise selection approach, the best model for M value prediction was applied to the validation cohort. This cohort was also divided into subgroups according to glucose tolerance, obesity category and age. The new index, called PREDIcted M (PREDIM), was based on OGIS, BMI, 2 h glucose during OGTT and fasting insulin. Bland-Altman analysis revealed a good relationship between the M value and PREDIM in the validation dataset (only 9 of 154 observations outside limits of agreement). Also, no significant differences were found between the M value and PREDIM (equivalence test: p < 0.0063). Subgroup stratification showed that measured M value and PREDIM have a similar ability to detect intergroup differences (p < 0.02, both M value and PREDIM). The new index PREDIM provides excellent prediction of M values from OGTT or meal data, thereby allowing comparison of insulin sensitivity between studies using different tests.

  6. Effects of insulin on glucose uptake and leg blood flow in patients with sickle cell disease and normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Serne, EH; Bakker, SJL; van Eps, WS; Donker, AJM; Gans, ROB

    The hemodynamic concept of insulin resistance assumes that vasodilatory effects of insulin determine glucose uptake. Sickle cell disease (SCD) is characterized by microangiopathy and microvascular occlusion. Therefore, we hypothesized that patients with SCD have a reduced insulin-mediated glucose

  7. Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness.

    Science.gov (United States)

    Kohno, Daisuke; Koike, Miho; Ninomiya, Yuzo; Kojima, Itaru; Kitamura, Tadahiro; Yada, Toshihiko

    2016-01-01

    The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes. T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10 -5 -10 -2 M dose dependently increased [Ca 2+ ] i in 12-16% of ARC neurons. The sucralose-induced [Ca 2+ ] i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca 2+ ] i increase was inhibited under an extracellular Ca 2+ -free condition and in the presence of an L-type Ca 2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC) neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular activation

  8. Insulin resistance and glucose levels in subjects with subclinical hypothyroidism

    International Nuclear Information System (INIS)

    Kahn, S.H.; Fazal, N.; Yasir, M.; Asif, N.; Rafi, T.

    2017-01-01

    To compare insulin resistance and glycemic indicators among subjects with euthyroidism and subclinical hypothyroidism. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Pathology and Medicine, PNS Hafeez, Islamabad, in collaboration with the Department of Chemical Pathology and Endocrinology at the Armed Forces Institute of Pathology (AFIP), Rawalpindi, from December 2015 to September 2016. Methodology: Subjects referred for executive screening of apparently healthy population (without any known history of diabetes, hypertension, heart disease or other chronic ailments), were included. Subjects were grouped as euthyroidism and subclinical hypothyroidism. Results: Median (IQR) insulin resistance indices including fasting insulin and Homeostasis Model Assessment for Insulin Resistance in subjects with group-1 (n=176, 87%, Thyroid Stimulating Hormone: 0.5 - 3.5 mIU/L) and group-2 (n=26, 13%, Thyroid Stimulating Hormone: 3.51 - 15 mIU/L) were 7.6 (6.70) vs. 11.4 (13.72, p=0.040) and 1.77 (1.79) vs. 2.8 (3.07, p=0.071). The median differences for fasting plasma glucose were 5.0 (1.0) in group-1 vs. 5.0 (1.47) for Group-2 [p=0.618], and glycated hemoglobin was 5.60 (1.1) vs. 5.60 (1.7, p=0.824). Homeostasis Model Assessment for beta sensitivity index in paradox showed slightly higher values for group-2 [median (IQR) 86.67 (92.94)] than group-1 [111.6 (189.64, p= 0.040)]. Conclusion: Measures of insulin resistance including Homeostasis Model Assessment for Insulin Resistance and fasting insulin levels were significantly different between subjects with euthyroidism and having subclinical hypothyroidism. (author)

  9. A randomized clinical trial comparing the effect of basal insulin and inhaled mealtime insulin on glucose variability and oxidative stress

    NARCIS (Netherlands)

    Siegelaar, S. E.; Kulik, W.; van Lenthe, H.; Mukherjee, R.; Hoekstra, J. B. L.; DeVries, J. H.

    2009-01-01

    To assess the effect of three times daily mealtime inhaled insulin therapy compared with once daily basal insulin glargine therapy on 72-h glucose profiles, glucose variability and oxidative stress in type 2 diabetes patients. In an inpatient crossover study, 40 subjects with type 2 diabetes were

  10. Impaired insulin-stimulated nonoxidative glucose metabolism in pancreas-kidney transplant recipients. Dose-response effects of insulin on glucose turnover

    DEFF Research Database (Denmark)

    Christiansen, E; Vestergaard, H; Tibell, A

    1996-01-01

    Insulin resistance is a characteristic feature in recipients of a pancreas transplant, but the relative contribution of the liver and peripheral tissues to this abnormality within a spanning range of insulin concentrations is unknown. To assess the impact of insulin action on glucose metabolism....... The overall effects of insulin on whole-body glucose metabolism, determined as the glucose infusion rates versus the corresponding steady-state serum insulin concentrations, demonstrated a rightward shift in the dose-response curves of the transplanted groups compared with those of normal subjects. The dose......, this finding could only explain in part the degree of impairment in nonoxidative glucose metabolism. No differences were found in total hexokinase activity in muscle between normal subjects and the transplant groups at basal insulinemia or after insulin stimulation. During hyperinsulinemia, glucagon...

  11. Impaired insulin-stimulated nonoxidative glucose metabolism in pancreas-kidney transplant recipients. Dose-response effects of insulin on glucose turnover

    DEFF Research Database (Denmark)

    Christiansen, E; Vestergaard, H; Tibell, A

    1996-01-01

    , this finding could only explain in part the degree of impairment in nonoxidative glucose metabolism. No differences were found in total hexokinase activity in muscle between normal subjects and the transplant groups at basal insulinemia or after insulin stimulation. During hyperinsulinemia, glucagon......Insulin resistance is a characteristic feature in recipients of a pancreas transplant, but the relative contribution of the liver and peripheral tissues to this abnormality within a spanning range of insulin concentrations is unknown. To assess the impact of insulin action on glucose metabolism....... The overall effects of insulin on whole-body glucose metabolism, determined as the glucose infusion rates versus the corresponding steady-state serum insulin concentrations, demonstrated a rightward shift in the dose-response curves of the transplanted groups compared with those of normal subjects. The dose...

  12. Closed-Loop Insulin Delivery Using a Subcutaneous Glucose Sensor and Intraperitoneal Insulin Delivery

    Science.gov (United States)

    Renard, Eric; Place, Jerome; Cantwell, Martin; Chevassus, Hugues; Palerm, Cesar C.

    2010-01-01

    OBJECTIVE Attempts to build an artificial pancreas by using subcutaneous insulin delivery from a portable pump guided by an subcutaneous glucose sensor have encountered delays and variability of insulin absorption. We tested closed-loop intraperitoneal insulin infusion from an implanted pump driven by an subcutaneous glucose sensor via a proportional-integral-derivative (PID) algorithm. RESEARCH DESIGN AND METHODS Two-day closed-loop therapy (except for a 15-min premeal manual bolus) was compared with a 1-day control phase with intraperitoneal open-loop insulin delivery, according to randomized order, in a hospital setting in eight type 1 diabetic patients treated by implanted pumps. The percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was the primary end point. RESULTS During the closed-loop phases, the mean ± SEM percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was significantly higher (39.1 ± 4.5 vs. 27.7 ± 6.2%, P = 0.05), and overall dispersion of blood glucose values was reduced among patients. Better closed-loop glucose control came from the time periods excluding the two early postprandial hours with a higher percentage of time in the 4.4–6.6 mmol/l range (46.3 ± 5.3 vs. 28.6 ± 7.4, P = 0.025) and lower mean blood glucose levels (6.9 ± 0.3 vs. 7.9 ± 0.6 mmol/l, P = 0.036). Time spent with blood glucose <3.3 mmol/l was low and similar for both investigational phases. CONCLUSIONS Our results demonstrate the feasibility of intraperitoneal insulin delivery for an artificial β-cell and support the need for further study. Moreover, according to a semiautomated mode, the features of the premeal bolus in terms of timing and amount warrant further research. PMID:19846796

  13. Effect of Ghrelin on Glucose-Insulin Homeostasis: Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Susana Sangiao-Alvarellos

    2010-01-01

    Full Text Available Ghrelin is a 28-amino-acid peptide that displays a strong growth hormone- (GH- releasing activity through the activation of the growth hormone secretagogue receptor (GHSR. The first studies about role of ghrelin were focused on its orexigenic ability, but despite indisputable pharmacological data, the evidence for a physiological role for ghrelin in the control of appetite is much less clear. Mice with targeted deletion of either ghrelin or the GHSR exhibit an essentially normal metabolic phenotype when fed a regular chow diet, suggesting that ghrelin may have a redundant role in the regulation of food intake. RNAs for ghrelin as well as GHSR are expressed in the pancreas of rats and humans and several studies propose that ghrelin could have an important function in glucose homeostasis and insulin release, independent of GH secretion. Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin. For this reason, at least theoretically, ghrelin and/or its signalling manipulation could be useful for the treatment or prevention of diseases of glucose homeostasis such as type 2 diabetes.

  14. Impact of diisobutyl phthalate and other PPAR agonists on steroidogenesis and plasma insulin and leptin levels in fetal rats

    DEFF Research Database (Denmark)

    Boberg, Julie; Metzdorff, Stine Broeng; Wortziger, Rasmus Henrik Sorgenfryd

    2008-01-01

    fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation....... DiBP and rosiglitazone additionally reduced fetal plasma insulin levels. In mates, DiBP reduced anogenital testosterone production and testicular expression of Insl-3 and genes related to steroidogenesis. distance, PPAR alpha mRNA levels were reduced by DiBP at GD 19 in testis and liver. In females......, DiBP increased anogenital distance and increased ovarian aromatase mRNA levels. This study reveals new targets for phthalates and parabens in fetal male and female rats and contributes to the increasing concern about adverse effects of human exposure to these compounds. (C) 2008 Elsevier Ireland Ltd...

  15. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans

    International Nuclear Information System (INIS)

    Baron, A.D.; Brechtel, G.; Wallace, P.; Edelman, S.V.

    1988-01-01

    In vivo glucose uptake can occur via two mechanisms, namely, insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). Although the principal tissue sites for IMGU are skeletal muscle, the tissue sites for NIMGU at a given serum glucose concentration are not known. To examine this issue, rates of whole body glucose uptake (Rd) were measured at basal and during glucose clamp studies performed at euglycemia (approximately 90 mg/dl) and hyperglycemia (approximately 220 mg/dl) in six lean healthy men. Studies were performed during hyperinsulinemia (approximately 70 microU/ml) and during somatostatin-induced insulinopenia to measure IMGU and NIMGU, respectively. During each study, leg glucose balance (arteriovenous catheter technique) was also measured. With this approach, rates of whole body skeletal muscle IMGU and NIMGU can be estimated, and the difference between overall Rd and skeletal muscle glucose uptake represents non-skeletal muscle Rd. The results indicate that approximately 20% of basal Rd is into skeletal muscle. During insulinopenia approximately 86% of body NIMGU occurs in non-skeletal muscle tissues at euglycemia. When hyperglycemia was created, whole body NIMGU increased from 128 +/- 6 to 213 +/- 18 mg/min (P less than 0.01); NIMGU into non-skeletal muscle tissues was 134 +/- 11 and 111 +/- 6 mg/min at hyperglycemia and euglycemia, respectively, P = NS. Therefore, virtually all the hyperglycemia induced increment in NIMGU occurred in skeletal muscle. During hyperinsulinemia, IMGU in skeletal muscle represented 75 and 95% of body Rd, at euglycemia and hyperglycemia, respectively

  16. An ancestral role for the mitochondrial pyruvate carrier in glucose-stimulated insulin secretion

    Directory of Open Access Journals (Sweden)

    Kyle S. McCommis

    2016-08-01

    Conclusions: Altogether, these studies suggest that the MPC plays an important and ancestral role in insulin-secreting cells in mediating glucose sensing, regulating insulin secretion, and controlling systemic glycemia.

  17. Hormonal and adiposity state of women with polycystic ovary syndrome: implication of adiponectin and leptin

    Directory of Open Access Journals (Sweden)

    Aleksandra Atanasova Boshku

    2016-12-01

    Full Text Available Obesity and insulin resistance are frequently seen comorbidities in patients with polycystic ovary syndrome (PCOS, affecting the already disturbed metabolism of these patients. Disturbed secretion of adiponectin and leptin could be one of the contributing factors of obesity and insulin resistance in patients with PCOS. The aim of this study was to determine the levels of adiponectin and leptin in PCOS patients, as well as their association with other components of the syndrome. This cross-sectional study determined clinical, hormonal, and biochemical markers in 61 women with PCOS and 56 controls. There was a statistically significant difference in adiponectin and leptin between the groups (p>0.001. There was a significant negative correlation between adiponectin, body mass index (BMI, and waist circumference (r= -0.478; -0.452, p<0.001 and a negative correlation with testosterone, free androgen index (FAI, insulin, and the homeostasis model assessment for insulin resistance (HOMA-IR. A positive correlation between adiponectin, sex hormone binding globulin (SHGB, and fasting glucose levels was present. Correlation analysis of leptin with other metabolic parameters showed a positive correlation with BMI, waist circumference, insulin, and HOMA-IR. A significant inverse correlation was present between leptin and SHGB. In conclusion, adiponectin and leptin may serve as potential biomarkers of insulin resistance. Determining levels of adiponectin and leptin in the early course of this syndrome may enable earlier diagnosis of insulin resistance, or even early prevention in PCOS patients.

  18. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility

    Directory of Open Access Journals (Sweden)

    Pikee Saxena

    2011-01-01

    Full Text Available Background : Insulin resistance (IR is central to the pathogenesis of polycystic ovarian syndrome (PCOS, but tests for determining IR are elaborate, tedious and expensive. Aims : To evaluate if "2-hour post-glucose insulin level" is an effective indicator of IR and can aid in diagnosing IR in infertile PCOS women. Settings and Design : Observational study at infertility clinic of a tertiary care center. Materials and Methods : 50 infertile women with PCOS and 20 females with tubal/male factor infertility were evaluated for the presence of IR, as defined by the fasting/2-hour post-glucose insulin levels cutoffs of >25/>41 μU/mL, respectively. The clinical, metabolic and endocrinologic profile was determined in both the groups. Statistical Analysis : Statistical analysis was performed using SPSS (Chicago, IL, USA. Results : Body mass index, post load glucose, insulin, glucose/insulin ratio, area under curve (AUC of glucose and insulin and insulinogenic index were significantly lower in the controls as compared to the PCOS group. "2-hour post-glucose insulin levels" were elevated in 88% of PCOS individuals but were normal in all females not suffering from PCOS. These levels significantly correlated with AUC of glucose and insulin, and insulinogenic index and inversely correlated with 2-hour glucose to insulin ratio (r=0.827, 0.749 and −0.732, respectively. Conclusions : "2-hour post-glucose insulin levels" appears to be a good indicator of IR. It can be a useful tool, especially in low resource setting where a single sample can confirm the diagnosis, thus reducing cost and repeat visits.

  19. Leptin Level in Women with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Alexander V. Dreval, PhD, ScD

    2013-06-01

    Full Text Available A detailed study of the dynamics of leptin in the various types of disturbances in carbohydrate metabolism could reveal its role in the pathogenesis of Type 2 Diabetes Mellitus (T2DM. The aim of this study was to investigate the Fasting Leptin Level (FLL and effect of acute hyperinsulinemia during the Intravenous Glucose Tolerance Test (IVGTT on the leptin levels in women with Insulin Resistance Syndrome (IRS. Materials and Methods: In total, 59 obese women (54.0 [48.5-60.0] yrs; BMI – 33.2 [29.0-37.2] kg/m² with IRS (12 – obesity (NGT, 18 - ITG and 30 - T2DM were observed. The IVGTT test was done only in women with impaired glucose tolerance (IGT and T2DM. The leptin level was investigated during fasting conditions and again 120 min post glucose loading. Then the Hepatic glucose production Index (H-index was calculated using the IVGTT data. Results: The FLL in women with normal glucose tolerance (NGT was almost two times greater than in women with IGT and T2DM. A negative relationship was found to exist between FLL and HbA1c in T2DM (r=0.3, p8%. The leptin level significantly decreased at 120 min of IVGTT in both the IGT and T2DM groups (p<0.05. Conclusion: The FLL depended upon the degree of glucose metabolism impairment; postprandial leptin response to the glucose load was lower in the IGT group than in the T2DM subjects.

  20. Two-way crossover comparison of insulin glargine and insulin detemir in basal-bolus therapy using continuous glucose monitoring

    Directory of Open Access Journals (Sweden)

    Abe S

    2011-07-01

    Full Text Available Shinya Abe1,2, Gaku Inoue1,2, Satoru Yamada1,3, Junichiro Irie1,3, Hiroyuki Nojima2, Kaoru Tsuyusaki2, Kensuke Usui2, Koichiro Atsuda2, Toshikazu Yamanouchi41Diabetes Center, Kitasato Institute Hospital, 2Center for Clinical Pharmacy and Clinical Sciences, Kitasato University, 3Department of Internal Medicine, Keio University School of Medicine, 4Department of Internal Medicine, University of Teikyo School of Medicine, Tokyo, JapanObjective: This study aimed to compare the glucose-lowering effect and glycemic variability of insulin glargine with those of insulin detemir.Material and methods: This was an open-label, single-center, randomized, two-way crossover study in patients with diabetes on basal-bolus insulin therapy, with neutral protamine Hagedorn (NPH insulin as basal insulin. Patients switched from NPH insulin to a course either of insulin glargine followed by insulin detemir, or insulin detemir followed by insulin glargine, continuing the same dose of the prior bolus of insulin. To evaluate the glucose-lowering effect, daily glycemic profiles were recorded for 72 hours by continuous glucose monitoring (CGM in an outpatient setting. The mean amplitude of glycemic excursions, standard deviation (SD, and the mean of daily difference (MODD were used to assess intraday and day-to-day glycemic variability.Results: Eleven patients were enrolled and nine completed the study. Mean blood glucose calculated from CGM values was significantly lower with insulin glargine compared with insulin detemir (9.6 ± 2.4 mmol/L versus 10.4 ± 2.8 mmol/L, P = 0.038. The SD was significantly lower with insulin glargine versus insulin detemir (2.5 ± 0.9 mmol/L vs 3.5 ± 1.6 mmol/L, P = 0.011. The MODD value was significantly lower with insulin glargine than with insulin detemir (2.2 ± 1.1 mmol/L vs 3.6 ± 1.7 mmol/L, P = 0.011. There was no significant difference between the two insulin analogs in terms of hypoglycemia.Conclusion: This study suggests that

  1. Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation.

    Science.gov (United States)

    Merli, M; Leonetti, F; Riggio, O; Valeriano, V; Ribaudo, M C; Strati, F; Tisone, G; Casciani, C U; Capocaccia, L; Sprati, F

    1999-09-01

    Cirrhosis is often associated with insulin resistance and glucose intolerance. We evaluated if these alterations are restored by liver transplantation (LT). Glucose tolerance (oral glucose tolerance test [OGTT]), peripheral insulin sensitivity (euglycemic insulin clamp technique), glucose oxidation (indirect calorimetry), nonoxidative glucose disposal, and insulin secretion (hyperglycemic clamp technique) were measured in 6 patients (Group 1) before and 6 months after LT, in 12 patients (Group 2) who underwent LT 6 to 30 months previously, and in 6 healthy individuals (controls). In Group 1, glucose tolerance and insulin sensitivity (3.24 +/- 0.37 mg/kg/min) were normalized after LT (8.6 +/- 0.77 mg/kg/min; P <.0001; P = not significant vs. controls). The improved insulin-mediated glucose uptake was the result of a normalization of nonoxidative glucose disposal. Fasting insulin and C-peptide decreased from 24.6 +/- 3.3 microU/mL and 4.37 +/- 0.46 ng/dL, respectively, to 12.7 +/- 1.9 microU/mL and 2.46 +/- 0.5 ng/dL (controls: 10.0 +/- 3 microU/mL and 1.45 +/- 0.34 ng/dL). The glucose-induced increase of insulin concentration, which was higher before LT, showed a significant reduction, although the first phase of beta-cell secretion remained significantly higher compared with that of controls. All these findings were also confirmed in Group 2. The present data indicate that LT normalizes glucose tolerance and insulin sensitivity in cirrhotic patients through an improvement of both hepatic glucose clearance and the peripheral glucose disposal. The latter effect may be the result of the correction of chronic hyperinsulinemia. An increased first-phase beta-cell insulin secretion in response to high glucose levels persists, suggesting that a memory of previous insulin resistance is maintained.

  2. Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

    DEFF Research Database (Denmark)

    Solomon, Thomas; Malin, Steven K; Karstoft, Kristian

    2014-01-01

    Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index...... used to determine oral glucose-stimulated insulin secretion (GSISOGTT), and DIOGTT was calculated as the product of SI OGTT and GSISOGTT. Our novel SI OGTT showed high agreement with clamp-derived insulin sensitivity (typical error = +3.6%; r = 0.69, P

  3. Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul

    2003-01-01

    not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.......We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp...

  4. Exogenous glucose administration impairs glucose tolerance and pancreatic insulin secretion during acute sepsis in non-diabetic mice.

    Directory of Open Access Journals (Sweden)

    Yoshio Watanabe

    Full Text Available OBJECTIVES: The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT. We next extended our findings using a cecal ligation and puncture (CLP sepsis model administered early parenteral glucose support. METHODS: Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg in the presence of saline or glucose infusion (100 µL/hr, and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs. MEASUREMENTS: AND MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL or sham mice receiving parenteral glucose (113 ± 3 mg/dL all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml. CONCLUSIONS: The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin

  5. Effects of Oral Glucose Load on Endothelial Function and on Insulin and Glucose Fluctuations in Healthy Individuals

    Directory of Open Access Journals (Sweden)

    A. Major-Pedersen

    2008-01-01

    Full Text Available Background/aims. Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied by endothelial dysfunction. We studied the effect of oral glucose load on insulin and glucose fluctuations, and on postprandial endothelial function in healthy individuals in order to better understand and cope with the postprandial state in insulin resistant individuals. Methods. We assessed post-oral glucose load endothelial function (flow mediated dilation, plasma insulin, and blood glucose in 9 healthy subjects. Results. The largest increases in delta FMD values (fasting FMD value subtracted from postprandial FMD value occurred at 3 hours after both glucose or placebo load, respectively: 4.80±1.41 (P = .009 and 2.34±1.47 (P = .15. Glucose and insulin concentrations achieved maximum peaks at one hour post-glucose load. Conclusion. Oral glucose load does not induce endothelial dysfunction in healthy individuals with mean insulin and glucose values of 5.6 mmol/L and 27.2 mmol/L, respectively, 2 hours after glucose load.

  6. Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects.

    Science.gov (United States)

    Ishibashi, Kenji; Onishi, Airin; Fujiwara, Yoshinori; Ishiwata, Kiichi; Ishii, Kenji

    2017-01-01

    Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images. Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated. Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4-5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24). This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images.

  7. Effects of Bisphenol A on glucose homeostasis and brain insulin signaling pathways in male mice.

    Science.gov (United States)

    Fang, Fangfang; Chen, Donglong; Yu, Pan; Qian, Wenyi; Zhou, Jing; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

    2015-02-01

    The potential effects of Bisphenol A (BPA) on peripheral insulin resistance have recently gained more attention, however, its functions on brain insulin resistance are still unknown. The aim of the present study was to investigate the effects of BPA on insulin signaling and glucose transport in mouse brain. The male mice were administrated of 100 μg/kg/day BPA or vehicle for 15 days then challenged with glucose and insulin tolerance tests. The insulin levels were detected with radioimmunoassay (RIA), and the insulin signaling pathways were investigated by Western blot. Our results revealed that BPA significantly increased peripheral plasma insulin levels, and decreased the insulin signals including phosphorylated insulin receptor (p-IR), phosphorylated insulin receptor substrate 1 (p-IRS1), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular regulated protein kinases (p-ERK1/2) in the brain, though insulin expression in both hippocampus and profrontal cortex was increased. In parallel, BPA exposure might contribute to glucose transport disturbance in the brain since the expression of glucose transporters were markedly decreased. In conclusion, BPA exposure perturbs the insulin signaling and glucose transport in the brain, therefore, it might be a risk factor for brain insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. [Leptin correlates with distribution of fatty tissue and plasma levels of insulin, testosterone and tumor necrosis factor alpha in perimenopausal women with increased testosterone level and central location of body fat].

    Science.gov (United States)

    Milewicz, Tomasz; Krzysiek, Józef; Janczak-Saif, Agnieszka; Sztefko, Krystyna

    2006-01-01

    The evaluation of the influence of testosterone and fat tissue distribution on the serum leptin levels in perimenopausal women. 93 perimenopausal women without HRT (age: 51.0 +/- 8.8 yrs, FSH: 68.0 +/- 49.4 IU/l, estradiol: 38.3 +/- 37.0 ng/1) were divided into group A - 63 women with serum testosterone level or = 0.6 ng/ml. Each group was later divided according to WHR into subgroup I (AI and BI) (WHR or = 0.8). Basic fasting serum levels of LH, FSH, PRL, estradiol, insulin, hGH, IGF-I, IGFBP-1, IGFBP-3, leptin, testosterone, DHEAS TNF-alpha and SHBG were measured by RIA kits. Total cholesterol, HDL and LDL cholesterol, as well as triglycerides plasma levels were measured. Statistical evaluation was carried out by ANOVA and linear regression. BMI, WHR and plasma DHEAS level were higher in group B vs. group A. The lowest hGH, HDL-cholesterol and the highest TNF-alpha levels were found in group BII. The relations leptin/BMI and leptin/body mass were found in each group. The inverse relation between leptin and IGFBP-1 was found in groups A and B. In group A the inverse relations leptin/HDL-cholesterol and leptin/ DHEAS were observed. In group B the direct leptin/testosterone and inverse leptin/IGF-I relations were found. In group AI the inverse leptin/DHEAS relation remained, while in group AII inverse leptin/HDL-cholesterol relation remained and reverse leptin/IGFBP-1 relation was significant. The direct leptin/testosterone, leptin/WHR and inverse leptin/TNF-alpha links were observed in group BII. The serum leptin level was linked to WHR, serum testosterone, insulin, TNF-alpha levels only in groups of perimenopausal women with such cardiovascular risk factors as high WHR, overweight, high serum TNF-alpha and testosterone levels.

  9. Estimation of glucose rate of appearance from cgs and subcutaneous insulin delivery in type 1 diabetes

    KAUST Repository

    Laleg-Kirati, Taous-Meriem

    2017-08-31

    Method and System for providing estimates of Glucose Rate of Appearance from the intestine (GRA) using continuous glucose sensor measurements (CGS) taken from the subcutaneous of a diabetes patient and the amount of insulin administered to the patient.

  10. A Study on the Glucose and Immunoreactive Insulin Response during Oral Glucose Tolerance Test in Patients with Chronic Liver Diseases

    International Nuclear Information System (INIS)

    Choe, Kang Won; Lee, Hong Kyu; Koh, Chang Soon; Lee, Mu Ho

    1973-01-01

    The blood glucose and plasma immunoreactive insulin (IRI) levels were measured during aral glucose tolerance test in 7 healthy subjects and 6 patients with chronic liver diseases. The glucose tolerance was impaired in 5 of the 6 patients and normal in I. Plasma IRI responses were markedly increased and delayed in all patients, suggesting endogenous insulin resistance. Patients with more glucose intolerance showed less increase in plasma IRI than the group with less intolerance. lt is suggested that some insulin antagonists may decrease the peripheral insulin sensitivity and stimulate compensatory hyperactivity of pancreatic islets. If the compensatory hyperactivity is inadequate due to gemetic predisposition to diabetes mellitus or exhaustion of β-cells of pancreatic islets, the glucose intolerance and overt diabetes mellitus may ensue.

  11. Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men.

    Science.gov (United States)

    Heni, Martin; Wagner, Robert; Kullmann, Stephanie; Gancheva, Sofiya; Roden, Michael; Peter, Andreas; Stefan, Norbert; Preissl, Hubert; Häring, Hans-Ulrich; Fritsche, Andreas

    2017-07-01

    Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6- 2 H 2 ]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis. © 2017 by the American Diabetes Association.

  12. Impact of diisobutyl phthalate and other PPAR agonists on steroidogenesis and plasma insulin and leptin levels in fetal rats

    International Nuclear Information System (INIS)

    Boberg, Julie; Metzdorff, Stine; Wortziger, Rasmus; Axelstad, Marta; Brokken, Leon; Vinggaard, Anne Marie; Dalgaard, Majken; Nellemann, Christine

    2008-01-01

    Endocrine disrupting chemicals can induce malformations and impairment of reproductive function in experimental animals and may have similar effects in humans. Recently, the environmental obesogen hypothesis was proposed, suggesting that environmental chemicals contribute to the development of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activated receptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation day (GD) 7-21 to diisobutyl phthalate (DiBP), butylparaben, perfluorooctanoate, or rosiglitazone (600, 100, 20, or 1 mg/kg bw/day, respectively). Endocrine endpoints were studied in offspring at GD 19 or 21. DiBP, butylparaben and rosiglitazone reduced plasma leptin levels in male and female offspring. DiBP and rosiglitazone additionally reduced fetal plasma insulin levels. In males, DiBP reduced anogenital distance, testosterone production and testicular expression of Insl-3 and genes related to steroidogenesis. PPARα mRNA levels were reduced by DiBP at GD 19 in testis and liver. In females, DiBP increased anogenital distance and increased ovarian aromatase mRNA levels. This study reveals new targets for phthalates and parabens in fetal male and female rats and contributes to the increasing concern about adverse effects of human exposure to these compounds

  13. Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.

    Science.gov (United States)

    Wartchow, Krista Minéia; Tramontina, Ana Carolina; de Souza, Daniela F; Biasibetti, Regina; Bobermin, Larissa D; Gonçalves, Carlos-Alberto

    2016-06-01

    Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.

  14. Mitochondrial GTP Regulates Glucose-Induced Insulin Secretion

    Science.gov (United States)

    Kibbey, Richard G.; Pongratz, Rebecca L.; Romanelli, Anthony J.; Wollheim, Claes B.; Cline, Gary W.; Shulman, Gerald I.

    2007-01-01

    Summary Substrate-level mitochondrial GTP (mtGTP) and ATP (mtATP) synthesis occurs by nucleotide-specific isoforms of the tricarboxylic acid (TCA) cycle enzyme succinyl CoA synthetase (SCS). Unlike mtATP, each molecule of glucose metabolized produces approximately one mtGTP in pancreatic β-cells independent of coupling with oxidative phosphorylation making mtGTP a potentially important fuel signal. siRNA suppression of the GTP-producing pathway (ΔSCS-GTP) reduced glucose-stimulated insulin secretion (GSIS) by 50%, whereas suppression of the parallel ATP-producing isoform (ΔSCS-ATP) increased GSIS by two-fold in INS-1 832/13 cells and cultured rat islets. Insulin secretion correlated with increases in cytosolic calcium but not with changes in NAD(P)H or the ATP/ADP ratio. These data suggest an important role for mtGTP in mediating GSIS in β-cells by modulation of mitochondrial metabolism possibly via influencing mitochondrial calcium. Furthermore, by virtue of its tight coupling to TCA oxidation rates, mtGTP production may serve as an important molecular signal of TCA cycle activity. PMID:17403370

  15. Glucose-responsive insulin by molecular and physical design

    Science.gov (United States)

    Bakh, Naveed A.; Cortinas, Abel B.; Weiss, Michael A.; Langer, Robert S.; Anderson, Daniel G.; Gu, Zhen; Dutta, Sanjoy; Strano, Michael S.

    2017-10-01

    The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes technology. The idea behind the GRI is to create a therapeutic that modulates its potency, concentration or dosing relative to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. From the perspective of the medicinal chemist, the GRI is also important as a generalized model of a potentially new generation of therapeutics that adjust potency in response to a critical therapeutic marker. The aim of this Perspective is to highlight emerging concepts, including mathematical modelling and the molecular engineering of insulin itself and its potency, towards a viable GRI. We briefly outline some of the most important recent progress toward this goal and also provide a forward-looking viewpoint, which asks if there are new approaches that could spur innovation in this area as well as to encourage synthetic chemists and chemical engineers to address the challenges and promises offered by this therapeutic approach.

  16. Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth.

    Science.gov (United States)

    Tirabanchasak, Sirapassorn; Siripunthana, Sukumarn; Supornsilchai, Vichit; Wacharasindhu, Suttipong; Sahakitrungruang, Taninee

    2015-09-01

    Subjects with impaired glucose tolerance (IGT) are at risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. The predictors of IGT in obese youth are not well described. We studied 115 obese Thai children who underwent an oral glucose tolerance test (OGTT). Plasma glucose and insulin levels were calculated for assessment of β-cell function. Hemoglobin A1c (HbA1c), lipid profile, and clinical parameters were also used to determine predictors of IGT. We found that three patients had T2DM and 30 subjects had IGT. IGT patients had significantly higher fasting glucose (FG), 1-h postload glucose, 2-h postload insulin, and lower whole-body insulin sensitivity indices than in normal glucose tolerance subjects whereas other indices were comparable. By ROC curve analyses, 1-h postload glucose was the best predictor of IGT, but FG or HbA1c represented a poor diagnostic tool for prediabetes screening. Subjects with 1-h OGTT glucose > 155 mg/dL had significantly lower high-density lipoprotein levels, lower insulin sensitivity, and more insulin resistance than those with 1-h postload glucose of ≤ 155 mg/dL. Abnormal glucose tolerance is highly prevalent in obese Thai youth. Several fasting indices and HbA1c fail to predict IGT. An 1-h OGTT glucose of > 155 mg/dL appears to be more associated with adverse insulin dynamics and metabolic profile than 2-h postload glucose.

  17. Triglycerides and glucose index: a useful indicator of insulin resistance.

    Science.gov (United States)

    Unger, Gisela; Benozzi, Silvia Fabiana; Perruzza, Fernando; Pennacchiotti, Graciela Laura

    2014-12-01

    Insulin resistance assessment requires sophisticated methodology of difficult application. Therefore, different estimators for this condition have been suggested. The aim of this study was to evaluate the triglycerides and glucose (TyG) index as a marker of insulin resistance and to compare it to the triglycerides/HDL cholesterol ratio (TG/HDL-C), in subjects with and without metabolic syndrome (MS). An observational, cross-sectional study was conducted on 525 adults of a population from Bahia Blanca, Argentina, who were divided into two groups: with MS (n=89) and without MS (n=436). The discriminating capacities for MS of the TyG index, calculated as Ln (TG [mg/dL] x glucose [mg/dL]/2), and the TG/HDL-C ratio were evaluated. Pre-test probability for MS was 30%. The mean value of the TyG index was higher in the group with MS as compared to the group without MS and its correlation with the TG/HDL-C ratio was good. The cut-off values for MS in the overall population were 8.8 for the TyG index (sensitivity=79%, specificity=86%), and 2.4 for the TG/HDL-C ratio (sensitivity=88%, specificity=72%). The positive likelihood ratios and post-test probabilities for these parameters were 5.8 vs 3.1 and 72% vs 58% respectively. The cut-off point for the TyG index was 8.8 in men and 8.7 in women; the respective values for TG/C-HDL were 3.1 in men and 2.2 in women. The TyG index was a good discriminant of MS. Its simple calculation warrants its further study as an alternative marker of insulin resistance. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

  18. Effects of glucose and insulin on fetal glucose oxidation and oxygen consumption

    International Nuclear Information System (INIS)

    Hay, W.W. Jr.; DiGiacomo, J.E.; Meznarich, H.K.; Hirst, K.; Zerbe, G.

    1989-01-01

    Glucose and insulin clamp experiments were performed in late-gestation fetal lambs to quantify the separate and combined effects of physiological concentrations of fetal glucose (G; 7.3-62.6 mg/dl) and insulin (I; 2-119 uU/ml) on fetal glucose metabolism and O2 consumption. Fetal glucose utilization rate (GUR) varied from 2.82 to 15.12 mg.min-1.kg-1. Fetal CO 2 production from fetal glucose carbon oxidation (CO 2 Pr) varied from 32 to 234 mumol.min-1.kg-1 and was directly related to G and I [CO 2 Pr = -0.00868 + 0.00578 (G) + 0.000901 (I) - 0.0000619 (G)2, r = 0.88] and to GUR (CO 2 Pr = 0.0159 GUR - 0.0130, r = 0.89). CO 2 Pr accounted for 54.7% of the mean GUR and for 35.9% of the mean umbilical O 2 uptake (UO2U), ranging from 26.0% in the control studies to 36.5% in hyperinsulinemic-euglycemic studies and to 45.1% in hyperinsulinemic-hyperglycemic studies. UO 2 U varied from 0.200 to I [UO 2 U = 0.303 + [0.000813 (G)] + [0.0000461 (I)], r = 0.89] and to GUR (UO2U = 0.0098 GUR + 0.275, r = 0.91). These results define independent (additive) effects of G and I on glucose oxidation in the late gestation fetal lamb and demonstrate the necessity for considering the levels of both G and I when studying these aspects of fetal metabolism

  19. Glucose uptake and pulsatile insulin infusion: euglycaemic clamp and [3-3H]glucose studies in healthy subjects

    International Nuclear Information System (INIS)

    Schmitz, O.; Arnfred, J.; Hother Nielsen, O.; Beck-Nielsen, H.; Oerskov, H.

    1986-01-01

    To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45mU/kg · min or in identical amounts in pulses of 1 1 / 2 to 2 1 / 4 min followed by intervals of 10 1 / 2 to 9 3 / 4 min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 μU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270-294 min: 8.7±0.7 vs 6.8±0.9 ml/kg · min, P 3 H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion. (author)

  20. Correlation of the leptin

    DEFF Research Database (Denmark)

    Finucane, F; Luan, J; Wareham, N

    2009-01-01

    AIMS/HYPOTHESIS: Obesity is the dominant cause of insulin resistance. In adult humans it is characterised by a combination of adipocyte hypertrophy and, to a lesser extent, adipocyte hyperplasia. As hypertrophic adipocytes secrete more leptin and less adiponectin, the plasma leptin......:adiponectin ratio (LAR) has been proposed as a potentially useful measure of insulin resistance and vascular risk. We sought to assess the usefulness of the LAR as a measure of insulin resistance in non-diabetic white adults. METHODS: Leptin and adiponectin levels were measured in 2,097 non-diabetic individuals...... from the Ely and European Group for the Study of Insulin Resistance (EGIR) Relationship between Insulin Sensitivity and Cardiovascular Risk (RISC) study cohorts. LAR was compared with fasting insulin and HOMA-derived insulin sensitivity (HOMA-S) in all individuals and with the insulin sensitivity index...

  1. Rosiglitazone treatment of patients with extreme insulin resistance and diabetes mellitus due to insulin receptor mutations has no effects on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H; Lund, S; Pedersen, O

    2001-01-01

    Rosiglitazone, a thiazolidinedione (TZD), increases insulin sensitivity by reducing levels of plasma NEFA, triglycerides (TG), glucose and serum insulin. Rosiglitazone treatment decreases insulin resistance in type 2 diabetic patients, but no data exist concerning rosiglitazone treatment of patie......Rosiglitazone, a thiazolidinedione (TZD), increases insulin sensitivity by reducing levels of plasma NEFA, triglycerides (TG), glucose and serum insulin. Rosiglitazone treatment decreases insulin resistance in type 2 diabetic patients, but no data exist concerning rosiglitazone treatment...

  2. Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.

    Directory of Open Access Journals (Sweden)

    Mimi Z Chen

    Full Text Available Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB, and compared this to lean volunteers.The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2 patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2. Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50 and maximal (GDR100 GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity.Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001. Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004 but not GDR100 (P=0.3. These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001. Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA, and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA, and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively.Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.

  3. Fasting leptin and glucose in normal weight, over weight and obese men and women diabetes patients with and without clinical depression.

    Science.gov (United States)

    Haleem, Darakhshan Jabeen; Sheikh, Shehnaz; Fawad, Asher; Haleem, Muhammad A

    2017-06-01

    A large number of diabetes patients suffer from major depression and are at high risk of mortality. In view of a role of leptin in diabetes, depression and energy homeostasis, the present study concerns circulating levels of leptin in different BMI groups of un-depressed and depressed diabetes patients. Six hundred thirty male and female patients with a primary diagnosis of diabetes were grouped according to BMI and with or without clinical symptoms of depression. Age matched healthy, normal weight male and female volunteers without clinical symptoms of depression or diabetes were taken as controls. Blood samples were obtained after an overnight fast of 12 h. Serum was stored for the determination of leptin and glucose. We found that there were more female than male diabetes patients with comorbid depression. Fasting leptin was higher in normal weight non-diabetes women than men; but comparable in normal weight men and women diabetes patients. Fasting glucose levels were higher in diabetes than non diabetes groups; values were comparable in men and women. Depression was associated with a decrease and increase in leptin respectively in normal-overweight and obese men and women diabetes patients. Glucose levels were also higher in obese depressed than un-depressed diabetes patients. The results suggested that the female gender is at greater risk to comorbid diabetes with depression. Adipo-insular axis plays an important role in diabetes, associated depression and in the greater risk of the female gender to comorbid diabetes with depression.

  4. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients.

    Science.gov (United States)

    Grasso, Alessandro; Malfatti, Federica; Andraghetti, Gabriella; Marenco, Simona; Mazzucchelli, Chiara; Labanca, Sara; Cordera, Renzo; Testa, Roberto; Picciotto, Antonino

    2015-01-01

    Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P = 0.033 and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

  5. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients

    Directory of Open Access Journals (Sweden)

    Alessandro Grasso

    2015-01-01

    Full Text Available Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P=0.033 and 0.048, resp. in patients who achieved an early viral load decay (EVR, a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

  6. Novel role of insulin in the regulation of glucose excretion by mourning doves (Zenaida macroura).

    Science.gov (United States)

    Sweazea, Karen L; Braun, Eldon J; Sparr, Richard

    2017-06-01

    In mammals, insulin primarily lowers plasma glucose (P Glu ) by increasing its uptake into tissues. Studies have also shown that insulin lowers P Glu in mammals by modulating glomerular filtration rate (GFR). Birds have naturally high P Glu and, although insulin administration significantly decreases glucose concentrations, birds are resistant to insulin-mediated glucose uptake into tissues. Since prior work has not examined the effects of insulin on GFR in birds, the purpose of the present study was to assess whether insulin can augment renal glucose excretion and thereby lower P Glu . Therefore, the hypothesis of the present study was that insulin lowers P Glu in birds by augmenting GFR, as estimated by inulin clearance (C In ). Adult mourning doves (Zenaida macroura) were used as experimental animals. Doves were anesthetized and the brachial vein was cannulated for administration of [ 14 C]-inulin and insulin and the brachial artery was cannulated for blood collections. Ureteral urine was collected via a catheter inserted into the cloaca. Ten minutes following administration of exogenous insulin (400μg/kg body mass, i.v.) plasma glucose was significantly decreased (p=0.0003). Twenty minutes following insulin administration, increases in GFR (p=0.016) were observed along with decreases in urine glucose concentrations (p=0.008), glucose excretion (p=0.028), and the fractional excretion of glucose (p=0.003). Urine flow rate (p=0.051) also tended to increase after administration of insulin. These data demonstrate a significant role for insulin in modulating GFR in mourning doves, which may in part explain the lower P Glu measured following insulin administration. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Effect of insulin and glucocorticoids on glucose transporters in rat adipocytes

    International Nuclear Information System (INIS)

    Carter-Su, C.; Okamoto, K.

    1987-01-01

    The ability of glucocorticoids to modify the effect of insulin on glucose (L-1- 3 H(N)]glucose and D-[ 14 C-U]glucose) transport was investigated in both intact isolated rat adipocytes and in membranes isolated from hormone-treated adipocytes. In intact adipocytes, dexamethasone, a potent synthetic glucocorticoid, inhibited insulin-stimulated 3-O-methylglucose transport at all concentrations of insulin tested. Insulin sensitivity, as well as the maximal response to insulin, was decreased by dexamethasone in the absence of a change in 125 I insulin binding. The inhibition was observed regardless of which hormone acted first, was blocked by actinomycin D, and resulted from a decrease in V/sub max/ rather than an increase in K/sub t/ of transport. In plasma membranes isolated from insulin-treated adipocytes, glucose transport activity and the amount of glucose transporter covalently labeled with [ 3 H]cytochalasin B were increased in parallel in a dose-dependent fashion. The amount of labeled transporter in a low-density microsomal fraction (LDMF) was decreased in a reciprocal fashion. In contrast, addition of dexamethasone to insulin-stimulated cells caused decreases in both transport activity and amount of labeled transporter in the plasma membranes. This was accompanied by a small increase in the amount of [ 3 H]cytochalasin B incorporated into the glucose transporter in the LDMF. These results are consistent with both insulin and glucocorticoids altering the distribution of glucose transporters between the plasma membrane and LDMF, in opposite directions

  8. Serum leptin and its relationship with metabolic variables in Arabs with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Al-Shoumer, Kamal A.; Doi, Suhail A.; Vasanthy, Bagavathy A.; Al-Asousi, Adnan A.

    2008-01-01

    Most studies on serum leptin in type 2 diabetes mellitus have focused on white populations. We studied serum leptin concentrations and parameters related to glycemic control and the association between leptin levels and anthropometric and metabolic factors in Arab patients with type 2 diabetes and in Arab control subjects. Ninety-two patients (65 females and 27 males) with type 2 diabetes and 69 matched normal and control subjects (48 females and 21 males) were included. Anthropometric measures (including body mass index (BMI) and waist: hip ratio) were assessed in all subjects. After an overnight fast, blood was collected for serum leptin assay. Other metabolic parameters include glucose, insulin, C-peptide, intact proinsulin, insulin resistance index (HOMA-IR), insulin-like growth factor 1 (IGF-1), lipids and hemoglobin A 1c (HbA) were determined. Fasting serum leptin levels, IGF-1 and high-density lipoprotein (HDL) cholesterol were similar in patients with type 2 diabetes and control subjects. When obese subjects (BMI>-30kg/m2) were analyzed separately, serum levels of leptin were significantly lower in patients compared to controls. In contrast, patients had higher fasting glucose, insulin, C-peptide, intact proinsulin, insulin resistance, total cholesterol, triglycerides, HbA, and a larger waist circumference and waist-to-hip ratio than controls. Serum leptin correlated positively with BM, negatively with waist-to-hip ratio, and demonstrated no relationship to other parameters. Patients with type 2 diabetes in an Arab ethnic population showed evidence of an unfavorable metabolic profile despite having leptin levels similar to controls. Obesity influences serum leptin levels more significantly in type 2 diabetes, in which leptin levels tends to be low. (author)

  9. Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise

    DEFF Research Database (Denmark)

    Dela, Flemming; Mikines, K J; Larsen, J J

    1999-01-01

    Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle tra...

  10. Is Insulin Action in the Brain Relevant in Regulating Blood Glucose in Humans?

    Science.gov (United States)

    Dash, Satya; Xiao, Changting; Morgantini, Cecilia; Koulajian, Khajag; Lewis, Gary F

    2015-07-01

    In addition to its direct action on the liver to lower hepatic glucose production, insulin action in the central nervous system (CNS) also lowers hepatic glucose production in rodents after 4 hours. Although CNS insulin action (CNSIA) modulates hepatic glycogen synthesis in dogs, it has no net effect on hepatic glucose output over a 4-hour period. The role of CNSIA in regulating plasma glucose has recently been examined in humans and is the focus of this review. Intransal insulin (INI) administration increases CNS insulin concentration. Hence, INI can address whether CNSIA regulates plasma glucose concentration in humans. We and three other groups have sought to answer this question, with differing conclusions. Here we will review the critical aspects of each study, including its design, which may explain these discordant conclusions. The early glucose-lowering effect of INI is likely due to spillover of insulin into the systemic circulation. In the presence of simultaneous portal and CNS hyperinsulinemia, portal insulin action is dominant. INI administration does lower plasma glucose independent of peripheral insulin concentration (between ∼3 and 6 h after administration), suggesting that CNSIA may play a role in glucose homeostasis in the late postprandial period when its action is likely greatest and portal insulin concentration is at baseline. The potential physiological role and purpose of this pathway are discussed in this review. Because the effects of INI are attenuated in patients with type 2 diabetes and obesity, this is unlikely to be of therapeutic utility.

  11. A population-based Bayesian approach to the minimal model of glucose and insulin homeostasis

    DEFF Research Database (Denmark)

    Andersen, Kim Emil; Højbjerre, Malene

    2005-01-01

    The minimal model was proposed in the late 1970s by Bergman et al. as a powerful model consisting of three differential equations describing the glucose and insulin kinetics of a single individual. Considering the glucose and insulin simultaneously, the minimal model is a highly ill-posed estimat...

  12. Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise

    DEFF Research Database (Denmark)

    Dela, Flemming; Mikines, K J; Larsen, J J

    1999-01-01

    Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle...

  13. Abalation of Ghrelin receptor in leptin-deficient mice has paradoxical effects on glucose homeostasis compared to Ghrelin-abalated Leptin-deficient mice

    Science.gov (United States)

    Ghrelin is produced predominantly in stomach and is known to be the endogenous ligand of the growth hormone secretagogue receptor (GHSR). Ghrelin is a GH stimulator and an orexigenic hormone. In contrast, leptin is an anorexic hormone, and leptin-deficient ob/ob mice are obese and diabetic. To study...

  14. The role of leptin in human lipid and glucose metabolism: the effects of acute recombinant human leptin infusion in young healthy males

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2011-01-01

    Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents.......Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents....

  15. Insulin secretion and glucose uptake by isolated islets of the hamster

    International Nuclear Information System (INIS)

    Dunbar, J.C.; McLaughlin, W.J.; Walsh, M.F.J.; Foa, P.P.

    1976-01-01

    Isolated pancreatic islets of normal hamsters were perfused either in a closed or in a open system. When the buffer was recirculated and the endogenous insulin was allowed to accumulate, the islets secreted significantly less insulin than when the system was open and the endogenous insulin was washed away. The addition of monocomponent insulin or of proinsulin to the perfusion buffer significantly decreased insulin secretion. The inhibitory action of proinsulin was significantly greater than that of monocomponent insulin. C peptide had no effect. When pancreatic islets were incubated in a fixed volume of stationary buffer containing unlabeled glucose (1.0 mg or 3.0 mg/ml) and glucose-U- 14 C (1.0 μC/ml), the amount of insulin secreted and the 14 CO 2 produced by each islet decreased progressively as the number of islets in the sample increased. Under these conditions, the concentration of insulin required to inhibit insulin secretion increased with the concentration of glucose in the medium. Proinsulin did not alter the incorporation of leucine-4.5- 3 H into total extractable insulin (insulin + proinsulin). Thus, insulin and proinsulin appear to inhibit insulin release, but not insulin synthesis. (orig.) [de

  16. Assessment and mathematical modeling of glucose turnover and insulin sensitivity in lean and obese cats.

    Science.gov (United States)

    Hoenig, M; Thomaseth, K; Brandao, J; Waldron, M; Ferguson, D C

    2006-11-01

    Insulin sensitivity (SI) of glucose disposal can be quantified with the euglycemic hyperinsulinemic clamp (EHC) with tracer glucose infusion. True steady state is, however, difficult to achieve, and non-steady state analysis of EHC data is preferred. This analysis requires information on glucose kinetics that can be obtained from bolus injection of cold and tracer glucose. The aim of this study was to assess glucose kinetics in cats. Mathematical modeling and non-steady state analysis was applied to assess effects of obesity on glucose turnover, glycolysis/glycogen synthesis, SI, and inhibition of endogenous glucose production (EGP) in lean cats (L) and obese cats (O). D-[3-(3)H]-glucose kinetics and 3H-H2O production were analyzed in 4 L and 4 O with three-compartment modeling. Frequently sampled insulin-modified intravenous glucose tolerance tests (FSIGT) with minimal model analysis were performed in 5L and 3 O to assess glucose kinetics and SI. EHC was performed in 10 L and 10 O with primed-constant infusion of 3H-glucose. Data were analyzed with a modified minimal model segregating suppression of EGP by insulin using a non-linear mixed-effects population approach. FSIGT provided estimates of SI, glucose effectiveness SG, and distribution volume. EHC provided estimates of SI, SG, glycolysis, and suprabasal insulin concentration for 50% EGP inhibition. Obesity appears to affect glucose distribution but not utilization at basal insulin, and reduces SI estimated by FSIGT and EHC. Differences in SI between FSIGT and EHC depend on different descriptions of EGP inhibition by insulin. Finally, glucose disposal at basal insulin appears to occur entirely through glycolysis, whereas significant amounts of glucose are sequestrated from oxidation during EHC.

  17. Intake of Lactobacillus reuteri Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans

    DEFF Research Database (Denmark)

    Simon, Marie-Christine; Strassburger, Klaus; Nowotny, Bettina

    2015-01-01

    OBJECTIVE: Ingestion of probiotics can modify gut microbiota and alter insulin resistance and diabetes development in rodents. We hypothesized that daily intake of Lactobacillus reuteri increases insulin sensitivity by changing cytokine release and insulin secretion via modulation of the release...... cytokines. CONCLUSIONS: Enrichment of gut microbiota with L. reuteri increases insulin secretion, possibly due to augmented incretin release, but does not directly affect insulin sensitivity or body fat distribution. This suggests that oral ingestion of one specific strain may serve as a novel therapeutic....... reuteri SD5865 or placebo over 4 weeks. Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess incretin effect and GLP-1 and GLP-2 secretion, and euglycemic-hyperinsulinemic clamps with [6,6-(2)H2]glucose were used to measure peripheral insulin sensitivity and endogenous glucose...

  18. Comparing glucose and insulin data from the two-hour oral glucose tolerance test in metabolic syndrome subjects and marathon runners.

    Science.gov (United States)

    Altuve, Miguel; Perpinan, Gilberto; Severeyn, Erika; Wong, Sara

    2016-08-01

    Glucose is the main energy source of the body's cells and is essential for normal metabolism. Two pancreatic hormones, insulin and glucagon, are involved in glucose home-ostasis. Alteration in the plasma glucose and insulin concentrations could lead to distinct symptoms and diseases, ranging from mental function impairment to coma and even death. Type 2 diabetes, insulin resistance and metabolic syndrome are typical examples of abnormal glucose metabolism that increase the risk for cardiovascular disease and mortality. The oral glucose tolerance test (OGTT) is a medical test used to screen for prediabetes, type 2 diabetes and insulin resistance. In the 5-sample 2-hour OGTT, plasma glucose and insulin concentrations are measured after a fast and then after oral intake of glucose, at intervals of 30 minutes. In this work, a statistical analysis is carried out to find significant differences between the five stages of the OGTT for plasma glucose and insulin data. In addition, the behavior of the glucose and insulin data is compared between subjects with the metabolic syndrome and marathon runners. Results show that marathon runners have plasma glucose and insulin levels significantly lower (p Insulin secretion decreases in marathon runners due to a significant reduction in plasma glucose concentration, but insulin secretion does not decrease in metabolic syndrome subjects due to insulin resistance, consequently plasma glucose concentration does not achieve normal levels.

  19. CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion.

    Science.gov (United States)

    Zheng, Hongzhi; Fu, Jingqi; Xue, Peng; Zhao, Rui; Dong, Jian; Liu, Dianxin; Yamamoto, Masayuki; Tong, Qingchun; Teng, Weiping; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E; Pi, Jingbo

    2015-04-01

    The inability of pancreatic β-cells to secrete sufficient insulin in response to glucose stimulation is a major contributing factor to the development of type 2 diabetes (T2D). We investigated both the in vitro and in vivo effects of deficiency of nuclear factor-erythroid 2-related factor 1 (Nrf1) in β-cells on β-cell function and glucose homeostasis. Silencing of Nrf1 in β-cells leads to a pre-T2D phenotype with disrupted glucose metabolism and impaired insulin secretion. Specifically, MIN6 β-cells with stable knockdown of Nrf1 (Nrf1-KD) and isolated islets from β-cell-specific Nrf1-knockout [Nrf1(b)-KO] mice displayed impaired glucose responsiveness, including elevated basal insulin release and decreased glucose-stimulated insulin secretion (GSIS). Nrf1(b)-KO mice exhibited severe fasting hyperinsulinemia, reduced GSIS, and glucose intolerance. Silencing of Nrf1 in MIN6 cells resulted in oxidative stress and altered glucose metabolism, with increases in both glucose uptake and aerobic glycolysis, which is associated with the elevated basal insulin release and reduced glucose responsiveness. The elevated glycolysis and reduced glucose responsiveness due to Nrf1 silencing likely result from altered expression of glucose metabolic enzymes, with induction of high-affinity hexokinase 1 and suppression of low-affinity glucokinase. Our study demonstrated a novel role of Nrf1 in regulating glucose metabolism and insulin secretion in β-cells and characterized Nrf1 as a key transcription factor that regulates the coupling of glycolysis and mitochondrial metabolism and GSIS. Nrf1 plays critical roles in regulating glucose metabolism, mitochondrial function, and insulin secretion, suggesting that Nrf1 may be a novel target to improve the function of insulin-secreting β-cells.

  20. Genome-wide analysis identifies colonic genes differentially associated with serum leptin and insulin concentrations in C57BL/6J mice fed a high-fat diet.

    Directory of Open Access Journals (Sweden)

    Sung-Eun Kim

    Full Text Available Obesity-induced chronic inflammation is known to increase the risk of ulcerative colitis, Crohn's disease, and colorectal cancer. Accumulating evidence suggests that leptin and insulin are key molecules linking obesity with diseases of the lower intestine. Here, we identified serum phenotype-associated genes in the colon of diet-induced obese mice as early biomarkers of obesity-associated colonic diseases. C57BL/6J mice were fed with either normal diet (ND, 15% of fat calories or high-fat diet (HFD, 45% of fat calories for 8 weeks. Serum concentrations of insulin, insulin-like growth factor-1 (IGF-1, leptin, and adiponectin were measured as obesity-related phenotypic markers. Genome-wide gene expression profiles of colon tissue were determined, followed by statistical analyses to detect differentially expressed and serum phenotype-associated genes. HFD-fed mice showed higher serum concentrations of leptin (P < 0.001 and insulin (P < 0.01 than those in the ND group, whereas serum IGF-1 and adiponectin concentrations did not differ between the two dietary groups. Among differentially expressed genes affected by HFD, 135, 128, 110, and 341 genes were associated with serum levels of leptin, insulin, IGF-1, and adiponectin, respectively. We identified 17 leptin-associated genes and 4 insulin-associated genes that inversely responded to HFD and ND. Among these, leptin-associated Peli3 (Pellino E3 ubiquitin protein ligase family member 3, Creb1 (cAMP responsive element binding protein 1, and Enpp2 (ectonucleotide pyrophosphatase/phosphodiesterase 2, autotaxin and insulin-associated Centg1 (AGAP2, ArfGAP with GTPase domain are reported to play a role either in obesity or colonic diseases. mRNA expression of these genes was validated by RT-qPCR. Our data suggest Peli3, Creb1, Enpp2, and Centg1 as potential early biomarker candidates for obesity-induced pathophysiological changes in the colon. Future studies verifying the function of these candidates are

  1. The role of insulin and glucagon in regulating glucose turnover in dogs during exercise.

    Science.gov (United States)

    Vranic, M; Kawamori, R; Wrenshall, G A

    1975-01-01

    During exercise the flux of glucose is regulated so that the increased demand of glucose by the muscle is met by a corresponding increased release of glucose by the liver; plasma glucose concentration does not change markedly, while glucose turnover increases. These precise regulatory mechanisms can be studied by quantitative isotope dilution methods; measurements of plasma glucose concentrations do not necessarily reflect any changes in glucose fluxes. Insulin is considered to be an important regulatory hormone during exercise. Its concentration decreases during exercise in part because of a decrease in insulin secretion by the pancreas and in part because the removal of insulin is increased. This conclusion was reached because insulin concentration in plasma decreased both in normal and in depancreatized insulin-infused dogs. A sudden decrease of portal insulin concentration facilitates glycogenolysis and gluconeogenesis in the liver. At the same time blood flow decreases in those areas which are inactive during exercise such as the splanchnic beds, while increased blood flow and opening of the capillary beds increases the total amount of insulin perfusing the muscle. Therefore, even in presence of low insulin concentration in plasma the insulin supply to the working muscle can presumably be maintained at an adequate level. We considered that exercise changes the distribution of insulin in relation to the liver and the muscle; such a distribution pattern may represent an important physiological regulatory mechanism. The question whether glucagon is essential in regulating glucose production during exercise could not be resolved because depancreatized insulin-infused dogs had essentially normal plasma concentrations of immunoreactive glucagon. Glucagon concentration increases during strenuous but not during moderate exercise of normal dogs. This increase is apparently not indispensable because during strenuous exercise depancreatized insulin-infused dogs did not

  2. Effect of fat supplementation on leptin, insulin-like growth factor I, growth hormone, and insulin in cattle

    OpenAIRE

    Becú-Villalobos, Damasia; García-Tornadú, Isabel; Shroeder, Guillermo; Salado, Eloy E.; Gagliostro, Gerardo; Delavaud, Carole; Chilliard, Yves; Lacau-Mengido, Isabel M.

    2007-01-01

    We investigated the effect of fat supplementation on plasma levels of hormones related to metabolism, with special attention to leptin, in cows in early lactation and in feedlot steers. In experiment 1, 34 lactating cows received no fat or else 0.5 or 1.0 kg of partially hydrogenated oil per day in addition to their basal diet from day 20 before the expected calving date to day 70 postpartum. In experiment 2, part of the corn in the basal concentrate was replaced with 0.7 kg of the same oil s...

  3. Optimal glucose-insulin control in H2 space.

    Science.gov (United States)

    Kovács, L; Paláncz, B; Almássy, Zs; Benyó, Z

    2004-01-01

    In this case study optimal glucose-insulin control in the Hardy H/sub 2/-space is presented for diabetic patients under intensive care. The analysis is based on a modified two-compartment model. First the classical LQ optimal control design method is considered, and then its extension the so called disturbance rejection LQR (LQ rejection) method, based on the MINIMAX differential game is applied to control design. To demonstrate the results of these two methods, the simulation of the dynamical performance of the non-linear closed loop system in case of food (sugar) intake has been carried out. For the symbolic and numeric computations Mathematica and Matlab-Simulink are used.

  4. Leptin, obesity and cardiovascular disease.

    Science.gov (United States)

    Correia, Marcelo Lima de Gusmao; Haynes, William Geoffrey

    2004-03-01

    Obesity is a risk factor for cardiovascular diseases. Leptin levels are increased in obesity and leptin exhibits cardiovascular actions that may contribute to increased cardiovascular risk. We review the sympathetic, renal and vascular actions of leptin and their relevance to cardiovascular disease. Leptin possesses cardio-renal actions potentially contributing to obesity-related hypertension including generalized sympathoactivation. However, given that leptin resistance occurs in obesity, it has been difficult to link hyperleptinemia with hypertension. One possibility is that leptin resistance is confined to the metabolic effects of leptin, with preservation of its sympathoexcitatory actions. Other mechanisms may contribute to the pressor effects of leptin. For instance, angiotensin II induces leptin generation. Leptin also potentiates the pressor effect of insulin. Therefore, interactions between angiotensin II and insulin with leptin could have deleterious cardiovascular effects in obesity. Additionally, leptin appears to stimulate vascular inflammation, oxidative stress and hypertophy. These actions may contribute to the pathogenesis of hypertension, atherosclerosis, and left ventricular hypertrophy. The potential actions of leptin in the pathophysiology of cardiovascular complications of obesity are diverse, despite evidence of leptin resistance to its metabolic actions. However, most information about cardiovascular actions of leptin derives from in-vitro and animal studies. Future research in humans is widely awaited.

  5. Effect of diet on insulin binding and glucose transport in rat sarcolemmal vesicles

    International Nuclear Information System (INIS)

    Grimditch, G.K.; Barnard, R.J.; Sternlicht, E.; Whitson, R.H.; Kaplan, S.A.

    1987-01-01

    The purpose of this study was to compare the effects of a high-fat, high-sucrose diet (HFS) and a low-fat, high-complex carbohydrate diet (LFC) on glucose tolerance, insulin binding, and glucose transport in rat skeletal muscle. During the intravenous glucose tolerance test, peak glucose values at 5 min were significantly higher in the HFS group; 0-, 20-, and 60-min values were similar. Insulin values were significantly higher in the HFS group at all time points (except 60 min), indicating whole-body insulin resistance. Skeletal muscle was responsible, in part, for this insulin resistance, because specific D-glucose transport in isolated sarcolemmal (SL) vesicles under basal conditions was similar between LFC and HFS rats, despite the higher plasma insulin levels. Scatchard analyses of insulin binding curves to sarcolemmal vesicles revealed that the K/sub a/ of the high-affinity binding sites was significantly reduced by the HFS diet; no other binding changes were noted. Specific D-glucose transport in SL vesicles after maximum insulin stimulation (1 U/kg) was significantly depressed in the HFS group, indicating that HFS feeding also caused a postbinding defect. These results indicate that the insulin resistance in skeletal muscle associated with a HFS diet is due to both a decrease in the K/sub a/ of the high-affinity insulin receptors and a postbinding defect

  6. Effects of Metformin on Serum Levels of Secreted Klotho and Leptin in PCOS Women

    Directory of Open Access Journals (Sweden)

    Savadali Saifi Novashnag

    2016-07-01

    Patients’ weights showed some decline. Fasting plasma glucose levels and insulin resistance decreased significantly (p<0.01. Hormonal assays indicated significant decrease in leptin and insulin levels and rise in Klotho levels. BMIs did not change meaningfully. Measurements of leptin and klotho levels showed a decrease in mean leptin levels from 34.74 to 28.41 ng/l and the level of klotho increased from 4.01 to 5.43 ng/l. Conclusion: This study showed that metformin treatment can cause a rise in klotho and a decrease in leptin levels without considerable effects on the weights of women with PCOS. Probably, leptin exerts its physiological effects in low concentrations while klotho in contrast acts physiologically in higher concentrations.

  7. Effects of glucose and insulin administration on glucose transporter expression in the North Pacific spiny dogfish (Squalus suckleyi).

    Science.gov (United States)

    Deck, Courtney A; Gary Anderson, W; Walsh, Patrick J

    2017-06-01

    Elasmobranchs (sharks, skates, and rays) are a primarily carnivorous group of fish, consuming few carbohydrates. Further, they tend to exhibit delayed responses to glucose and insulin administration in vivo relative to mammals, leading to a presumption of glucose-intolerance. To investigate the glucoregulatory capabilities of the spiny dogfish (Squalus suckleyi), plasma glucose concentration, muscle and liver glycogen content, and glucose transporter (glut1 and 4) mRNA levels were measured following intra-arterial administration of bovine insulin (10ngkg -1 ) or an approximate doubling of fasting plasma glucose concentration. Within 6h, following glucose administration, approximately half of the introduced glucose load had been cleared, with control levels being restored by 24h post-injection. It was determined that plasma clearance was due in part to increased uptake by the tissues as muscle and liver glycogen content increased significantly, correlating with an upregulation of glut mRNA levels. Following administration of bovine insulin, plasma glucose steadily decreased through 18h before returning toward control levels. Observed decreases in plasma glucose following insulin injection were, however, relatively minor, and no increases in tissue glycogen content were observed. glut4 and glycogen synthase mRNA levels did significantly increase in the muscle in response to insulin, but no changes occurred in the liver. The responses observed mimic what occurs in mammals and teleosts, thus suggesting a conserved mechanism for glucose homeostasis in vertebrates and a high degree of glucose tolerance in these predominantly carnivorous fish. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Closed-loop controlled noninvasive ultrasonic glucose sensing and insulin delivery

    Science.gov (United States)

    Park, Eun-Joo; Werner, Jacob; Jaiswal, Devina; Smith, Nadine Barrie

    2010-03-01

    To prevent complications in diabetes, the proper management of blood glucose levels is essential. Previously, ultrasonic transdermal methods using a light-weight cymbal transducer array has been studied for noninvasive methods of insulin delivery for Type-1 diabetes and glucose level monitoring. In this study, the ultrasound systems of insulin delivery and glucose sensing have been combined by a feedback controller. This study was designed to show the feasibility of the feedback controlled ultrasound system for the noninvasive glucose control. For perspective human application, in vivo experiments were performed on large animals that have a similar size to humans. Four in vivo experiments were performed using about 200 lbs pigs. The cymbal array of 3×3 pattern has been used for insulin delivery at 30 kHz with the spatial-peak temporal-peak intensity (Isptp) of 100 mW/cm2. For glucose sensing, a 2×2 array was operated at 20 kHz with Isptp = 100 mW/cm2. Based on the glucose level determined by biosensors after the ultrasound exposure, the ultrasound system for the insulin delivery was automatically operated. The glucose level of 115 mg/dl was set as a reference value for operating the insulin delivery system. For comparison, the glucose levels of blood samples collected from the ear vein were measured by a commercial glucose meter. Using the ultrasound system operated by the close-loop, feed-back controller, the glucose levels of four pigs were determined every 20 minutes and continuously controlled for 120 minutes. In comparison to the commercial glucose meter, the glucose levels determined by the biosensor were slightly higher. The results of in vivo experiments indicate the feasibility of the feedback controlled ultrasound system using the cymbal array for noninvasive glucose sensing and insulin delivery. Further studies on the extension of the glucose control will be continued for the effective method of glucose control.

  9. LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol.

    Science.gov (United States)

    Nøhr, Mark K; Dudele, Anete; Poulsen, Morten M; Ebbesen, Lene H; Radko, Yulia; Christensen, Lars P; Jessen, Niels; Richelsen, Bjørn; Lund, Sten; Pedersen, Steen B

    2016-01-01

    Low-grade inflammation is seen with obesity and is suggested to be a mediator of insulin resistance. The eliciting factor of low-grade inflammation is unknown but increased permeability of gut bacteria-derived lipopolysaccharides (LPS) resulting in endotoxemia could be a candidate. Here we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous) together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b, whereas the increased macrophage infiltration was unaltered) without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during an oral glucose tolerance test was increased despite similar plasma glucose level resulting in an increase in the insulinogenic index (IGI; delta0-15insulin/delta0-15glucose) from 13.73 to 22.40 pmol/mmol (P insulin and glucose homeostasis was normalized by resveratrol. Low-dose LPS enhanced the glucose-stimulated insulin secretion without affecting the blood glucose suggesting increased insulin resistance. Resveratrol restored LPS-induced alteration of the insulin secretion and demonstrated anti-inflammatory effects specifically in epididymal adipose tissue possibly due to preferential accumulation of resveratrol metabolites pointing towards a possible important involvement of this tissue for the effects on insulin resistance and insulin secretion.

  10. LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol.

    Directory of Open Access Journals (Sweden)

    Mark K Nøhr

    Full Text Available Low-grade inflammation is seen with obesity and is suggested to be a mediator of insulin resistance. The eliciting factor of low-grade inflammation is unknown but increased permeability of gut bacteria-derived lipopolysaccharides (LPS resulting in endotoxemia could be a candidate. Here we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b, whereas the increased macrophage infiltration was unaltered without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during an oral glucose tolerance test was increased despite similar plasma glucose level resulting in an increase in the insulinogenic index (IGI; delta0-15insulin/delta0-15glucose from 13.73 to 22.40 pmol/mmol (P < 0.001. This aberration in insulin and glucose homeostasis was normalized by resveratrol.Low-dose LPS enhanced the glucose-stimulated insulin secretion without affecting the blood glucose suggesting increased insulin resistance. Resveratrol restored LPS-induced alteration of the insulin secretion and demonstrated anti-inflammatory effects specifically in epididymal adipose tissue possibly due to preferential accumulation of resveratrol metabolites pointing towards a possible important involvement of this tissue for the effects on insulin resistance and insulin secretion.

  11. Role of insulin-like growth factor binding protein-3 in glucose and lipid metabolism

    Directory of Open Access Journals (Sweden)

    Ho-Seong Kim

    2013-03-01

    Full Text Available Insulin-like growth factor binding protein (IGFBP-3 has roles in modulating the effect of IGFs by binding to IGFs and inhibiting cell proliferation in an IGF-independent manner. Although recent studies have been reported that IGFBP-3 has also roles in metabolic regulation, their exact roles in adipose tissue are poorly understood. In this review, we summarized the studies about the biological roles in glucose and lipid metabolism. IGFBP-3 overexpression in transgenic mice suggested that IGFBP-3 results in glucose intolerance, and insulin resistance. IGFBP-3 knockout (KO mice exhibited normal insulin level and glucose response after glucose challenge. More recent study in IGFBP-3 KO mice with a high-fat diet demonstrated that IGFBP-3 KO mice exhibited elevated fasting glucose and insulin, but normal response to glucose challenge, suggesting that IGFBP-3 KO mice may induce insulin resistance even though preserved insulin sensitivity. In vitro and in vivo studies using 3T3-L1 adipocytes and rat, IGFBP-3 induced insulin resistance by inhibiting glucose uptake. In contrast, the reduced levels of IGFBP-3 in obesity might induce insulin resistance by suppression of IGFBP-3's anti-inflammatory function, suggesting IGFBP-3 has a protective effect on insulin resistance. Also, proteolysis of IGFBP-3 might contribute to the insulin resistance in obesity and type 2 diabetes mellitus. In addition, IGFBP-3 inhibited adipocyte differentiation, suggesting IGFBP-3 may contribute to the insulin insensitivity. Taken together, it is not yet certain that IGFBP-3 has a protective effect or enhancing effect on insulin resistance, and more studies will be needed to clarify the roles of IGFBP-3 in metabolic regulation.

  12. Inflammatory Properties of Diet and Glucose-Insulin Homeostasis in a Cohort of Iranian Adults

    Directory of Open Access Journals (Sweden)

    Nazanin Moslehi

    2016-11-01

    Full Text Available We aimed to investigate associations of the dietary inflammatory index (DII with glucose-insulin homeostasis markers, and the risk of glucose intolerance. This cross-sectional study included 2975 adults from the Tehran Lipid and Glucose Study. Fasting plasma glucose (FPG, 2-h post-load glucose (2h-PG, and fasting serum insulin were measured. Homeostatic model assessment of insulin resistance index (HOMA-IR and β-cell function (HOMA-B, and the quantitative insulin sensitivity check index (QUICKI were calculated. Glucose tolerance abnormalities included impaired fasting glucose (IFG, impaired glucose tolerance (IGT, and type 2 diabetes (T2DM. DII scores were positively associated with 2h-PG (β = 0.04; p = 0.05. There was no significant linear trend across quartiles of DII for adjusted means of glucose-insulin homeostasis markers. Participants in the highest quartile of DII score tended to have higher FPG compared to those in the second quartile of DII score (5.46 vs. 5.38 mmol/L, p = 0.07 and higher fasting insulin and HOMA-IR compared to those in the lowest quartile (8.52 vs. 8.12 µU/mL for fasting insulin, p = 0.07; 2.06 vs. 1.96 for HOMA-IR, p = 0.08. No significant associations were observed between DII and risk of IFG, IGT, T2DM, and insulin resistance. Among glucose-insulin homeostasis markers, DII had a positive weak association only with 2h-PG.

  13. Analysis of the relationship of leptin, high-sensitivity C-reactive protein, adiponectin, insulin, and uric acid to metabolic syndrome in lean, overweight, and obese young females.

    Science.gov (United States)

    Abdullah, Abdul Ridha; Hasan, Haydar A; Raigangar, Veena L

    2009-02-01

    Over the last decade there has been a steady rise in obesity and co-morbidity, but little is known about the rate of metabolic dysfunction among young adults in the United Arab Emirates. Various factors have been implicated as biomarkers of metabolic syndrome. The objective of this study was to analyze the relationships of leptin, C-reactive protein (CRP), adiponectin, insulin, and uric acid to the metabolic syndrome components in lean, overweight, and obese young females. This was a cross-sectional study of 69 apparently healthy young females, who were classified according to their body mass index (BMI) (kg/m(2)) into three groups: lean (25 and or=30). Estimated biomarkers were: leptin, insulin, adiponectin, high-sensitivity [hs]-CRP, uric acid, blood sugar, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides (TG). Anthropometric measures, blood pressure, and homeostasis model assessment-insulin resistance (HOMA-IR) were also measured. Serum leptin, hs-CRP, insulin, and uric acid increased significantly (p metabolic syndrome components was found in lean subjects (leptin vs. waist circumference r = 0.48) as opposed to six in the obese group (hs-CRP vs. waist circumference and systolic blood pressure [SBP], r = 0.45 and r = -0.41, respectively; insulin vs. diastolic blood pressure [DBP], r = 0.47; adiponectin vs. blood sugar, r = -0.44; and uric acid vs. waist circumference and TG, r = 0.5 and r = 0.51, respectively). Estimation of the levels of studied biomarkers could be an important tool for early detection of metabolic syndrome before the appearance of its frank components. Uric acid seems to be the most reliable biomarker to identify obese subjects with metabolic syndrome.

  14. Significance of insulin for glucose metabolism in skeletal muscle during contractions

    DEFF Research Database (Denmark)

    Hespel, P; Vergauwen, Lieven; Vandenberghe, K

    1996-01-01

    Glucose uptake rate in active skeletal muscles is markedly increased during exercise. This increase reflects a multifactorial process involving both local and systemic mechanisms that cooperate to stimulate glucose extraction and glucose delivery to the muscle cells. Increased glucose extraction...... is effected primarily via mechanisms exerted within the muscle cell related to the contractile activity per se. Yet contractions become a more potent stimulus of muscle glucose uptake as the plasma insulin level is increased. In addition, enhanced glucose delivery to muscle, which during exercise...... is essentially effected via increased blood flow, significantly contributes to stimulate glucose uptake. Again, however, increased glucose delivery appears to be a more potent stimulus of muscle glucose uptake as the circulating insulin level is increased. Furthermore, contractions and elevated flow prove...

  15. Vitamin D Status, Insulin Resistance, Leptin-To-Adiponectin Ratio in Adolescents: Results of a 1-Year Lifestyle Intervention

    Science.gov (United States)

    Rambhojan, Christine; Larifla, Laurent; Clepier, Josiane; Bouaziz-Amar, Elodie; Velayoudom-Cephise, Fritz-Line; Blanchet-Deverly, Anne; Armand, Christophe; Plumasseau, Jean; Lacorte, Jean-Marc; Foucan, Lydia

    2016-01-01

    AIM: We aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D], insulin resistance and leptin-to-adiponectin (L/A) ratio in Guadeloupean children and adolescents and to analyse the changes in 25(OH)D levels after a 1-year lifestyle intervention program. METHODS: 25(OH)D concentrations were measured via a chemiluminescence assay. Cardiometabolic risk factors, homoeostasis model assessment of insulin resistance (HOMA-IR), and adipokines were measured. The lifestyle intervention included dietary counselling, regular physical activity. RESULTS: Among 117 girls and boys (11–15 years old, 31.6% obese), 40% had vitamin D deficiency (25(OH)D levels HOMA-IR acted as independent variables and age, sex, BMI, L/A ratio as covariates, 25(OH)D was significantly associated with HOMA-IR alone (P = 0.036). HOMA-IR was also associated with BMI z-score ≥ 2, L/A ratio and an interaction term BMI z-score ≥ 2*L/A ratio (P HOMA-IR and L/A ratio decreased significantly (P = 0.003, P HOMA-IR, independently of obesity and the high prevalence of vitamin D deficiency should be considered in order to prevent the later incidence of T2DM. A healthy lifestyle including non-sedentary and outdoor activities could be a way for improving vitamin D status. PMID:28028397

  16. Wortmannin inhibits both insulin- and contraction-stimulated glucose uptake and transport in rat skeletal muscle

    DEFF Research Database (Denmark)

    Wojtaszewski, Jørgen; Hansen, B F; Ursø, Birgitte

    1996-01-01

    stimulation but was unaffected by contractions. In addition, the insulin-stimulated PI 3-kinase activity and muscle glucose uptake and transport in individual muscles were dose-dependently inhibited by wortmannin with one-half maximal inhibition values of approximately 10 nM and total inhibition at 1 micro......The role of phosphatidylinositol (PI) 3-kinase for insulin- and contraction-stimulated muscle glucose transport was investigated in rat skeletal muscle perfused with a cell-free perfusate. The insulin receptor substrate-1-associated PI 3-kinase activity was increased sixfold upon insulin......-stimulated glucose uptake but also decreased the contractility. In conclusion, inhibition of PI 3-kinase with wortmannin in skeletal muscle coincides with inhibition of insulin-stimulated glucose uptake and transport. Furthermore, in contrast to recent findings in incubated muscle, wortmannin also inhibited...

  17. Glucose responsive insulin production from human embryonic germ (EG) cell derivatives

    International Nuclear Information System (INIS)

    Clark, Gregory O.; Yochem, Robert L.; Axelman, Joyce; Sheets, Timothy P.; Kaczorowski, David J.; Shamblott, Michael J.

    2007-01-01

    Type 1 diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and β-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation of preproinsulin mRNA and expression of insulin C-peptide in vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes

  18. Effects of intravenous lipopolysaccharide infusion on glucose and insulin dynamics in horses with equine metabolic syndrome.

    Science.gov (United States)

    Tadros, Elizabeth M; Frank, Nicholas; De Witte, Fiamma Gomez; Boston, Raymond C

    2013-07-01

    To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). 6 healthy adult mares and 6 horses with EMS. Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were assessed via minimal model analysis and area under the curve values for plasma glucose and serum insulin concentrations. Lipopolysaccharide infusion decreased insulin sensitivity and increased area under the serum insulin concentration curve (treatment × time) in both healthy and EMS-affected horses, compared with findings following saline solution administration. The magnitude of increase in area under the plasma glucose curve following LPS administration was greater for the EMS-affected horses than it was for the healthy horses. Horses with EMS that received LPS or saline solution infusions had decreased insulin sensitivity over time. Glucose and insulin responses to endotoxemia differed between healthy horses and horses with EMS, with greater loss of glycemic control in EMS-affected horses. Horses with EMS also had greater derangements in glucose and insulin homeostasis that were potentially stress induced. It may therefore be helpful to avoid exposure of these horses to stressful situations.

  19. Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    James R. Krycer

    2017-12-01

    Full Text Available Insulin triggers an extensive signaling cascade to coordinate adipocyte glucose metabolism. It is considered that the major role of insulin is to provide anabolic substrates by activating GLUT4-dependent glucose uptake. However, insulin stimulates phosphorylation of many metabolic proteins. To examine the implications of this on glucose metabolism, we performed dynamic tracer metabolomics in cultured adipocytes treated with insulin. Temporal analysis of metabolite concentrations and tracer labeling revealed rapid and distinct changes in glucose metabolism, favoring specific glycolytic branch points and pyruvate anaplerosis. Integrating dynamic metabolomics and phosphoproteomics data revealed that insulin-dependent phosphorylation of anabolic enzymes occurred prior to substrate accumulation. Indeed, glycogen synthesis was activated independently of glucose supply. We refer to this phenomenon as metabolic priming, whereby insulin signaling creates a demand-driven system to “pull” glucose into specific anabolic pathways. This complements the supply-driven regulation of anabolism by substrate accumulation and highlights an additional role for insulin action in adipocyte glucose metabolism.

  20. The Effect of 12-Week Exercise with Omega-3 Supplement Consumption on Serum Level Changes of Adiponectin, Leptin, and Insulin in Girls

    Directory of Open Access Journals (Sweden)

    F. Piroozan

    2015-07-01

    Full Text Available Introduction & Objective: Adiponectin and leptin are peptide hormones regulating the energy balance. Therefore, the present study aims to identify the possible mechanisms of the effect of omega-3 and aerobic exercise on the balance of these two hormones. Materials & Methods: 60 healthy young women with the average age of 23.4±1.8 and the average weight of 60.45±5.85 were randomly selected and divided into training, omega 3-training, omega-3 and control groups. A basketball training program was performed including specialized training 3 times a week for 90 minutes. During the 12 weeks of training, omega-3+exercise and omega -3 groups were fed a number of oral capsules of omega-3 every night. Blood samples were taken from the brachial vein. To analyze the data and determine the relationship, one way ANOVA and Tukey test and Pearson's correlation coefficient were used. Results: Significant differences in serum levels of adiponectin, leptin and insulin secretion in exercise, omega-3 and exercise+omega-3 groups were observed. However, there was a significant correlation between changes in serum levels of adiponectin, and leptin and insulin secretion was not observed in any of the groups. Conclusion: It seems that omega-3 fatty acid intake with exercise enhances fat metabolism and is helpful to regulate the secretion of adiponectin and leptin hormone.(Sci J Hamadan Univ Med Sci 2015; 22 (2: 129-136

  1. Increased plasma leptin attenuates adaptive metabolism in early lactating dairy cows.

    Science.gov (United States)

    Ehrhardt, Richard A; Foskolos, Andreas; Giesy, Sarah L; Wesolowski, Stephanie R; Krumm, Christopher S; Butler, W Ronald; Quirk, Susan M; Waldron, Matthew R; Boisclair, Yves R

    2016-05-01

    Mammals meet the increased nutritional demands of lactation through a combination of increased feed intake and a collection of adaptations known as adaptive metabolism (e.g., glucose sparing via insulin resistance, mobilization of endogenous reserves, and increased metabolic efficiency via reduced thyroid hormones). In the modern dairy cow, adaptive metabolism predominates over increased feed intake at the onset of lactation and develops concurrently with a reduction in plasma leptin. To address the role of leptin in the adaptive metabolism of early lactation, we asked which adaptations could be countered by a constant 96-h intravenous infusion of human leptin (hLeptin) starting on day 8 of lactation. Compared to saline infusion (Control), hLeptin did not alter energy intake or milk energy output but caused a modest increase in body weight loss. hLeptin reduced plasma glucose by 9% and hepatic glycogen content by 73%, and these effects were associated with a 17% increase in glucose disposal during an insulin tolerance test. hLeptin attenuated the accumulation of triglyceride in the liver by 28% in the absence of effects on plasma levels of the anti-lipolytic hormone insulin or plasma levels of free fatty acids, a marker of lipid mobilization from adipose tissue. Finally, hLeptin increased the plasma concentrations of T4 and T3 by nearly 50% without affecting other neurally regulated hormones (i.e., cortisol and luteinizing hormone (LH)). Overall these data implicate the periparturient reduction in plasma leptin as one of the signals promoting conservation of glucose and energy at the onset of lactation in the energy-deficient dairy cow. © 2016 Society for Endocrinology.

  2. Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

    Energy Technology Data Exchange (ETDEWEB)

    Kofoed, Klaus F.; Hove, Jens D.; Freiberg, Jacob; Hoest, Ulla; Kelbaek, Henning [Cardiovascular PET Research Unit, Section 9201, Medical Department B, The Heart Center, Rigshospitalet, University of Copenhagen, Juliane Mariesvej 24, 2100 Copenhagen (Denmark); Holm, Soeren [The Cyclotron and PET Unit, Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, University of Copenhagen (Denmark)

    2002-12-01

    The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure, bicycle exercise test, electrocardiogram and echocardiography were studied [P(coronary artery disease) <5%]. Whole-body insulin sensitivity and insulin-stimulated myocardial glucose uptake were measured during hyperinsulinaemic euglycaemic glucose clamp with fluorine-18 fluorodeoxyglucose, and myocardial rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole-body insulin sensitivity (r=0.51, P<0.05 and r=0.56, P<0.01). The strongest independent association by multivariate linear regression analysis was found between myocardial glucose uptake and hyperaemic blood flow (r=0.63, P<0.005). We conclude that in healthy elderly subjects, insulin-stimulated myocardial glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity. (orig.)

  3. Differential Role of Insulin/IGF-1 Receptor Signaling in Muscle Growth and Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Brian T. O’Neill

    2015-05-01

    Full Text Available Insulin and insulin-like growth factor 1 (IGF-1 are major regulators of muscle protein and glucose homeostasis. To determine how these pathways interact, we generated mice with muscle-specific knockout of IGF-1 receptor (IGF1R and insulin receptor (IR. These MIGIRKO mice showed >60% decrease in muscle mass. Despite a complete lack of insulin/IGF-1 signaling in muscle, MIGIRKO mice displayed normal glucose and insulin tolerance. Indeed, MIGIRKO mice showed fasting hypoglycemia and increased basal glucose uptake. This was secondary to decreased TBC1D1 resulting in increased Glut4 and Glut1 membrane localization. Interestingly, overexpression of a dominant-negative IGF1R in muscle induced glucose intolerance in MIGIRKO animals. Thus, loss of insulin/IGF-1 signaling impairs muscle growth, but not whole-body glucose tolerance due to increased membrane localization of glucose transporters. Nonetheless, presence of a dominant-negative receptor, even in the absence of functional IR/IGF1R, induces glucose intolerance, indicating that interactions between these receptors and other proteins in muscle can impair glucose homeostasis.

  4. Control of hepatic glucose output by glucagon and insulin in the intact dog.

    Science.gov (United States)

    Cherrington, A D; Chiasson, J L; Liljenquist, J E; Lacy, W W; Park, C R

    1978-01-01

    The regulation of hepatic glucose production by glucagon and insulin has been studied in the intact dog. An attempt has been made to evaluate the role of basal physiological concentrations of the hormones in the regulation of glycogenolysis and gluconeogenesis. Somatostatin was infused continuously into postabsorptive dogs to inhibit the secretion of both glucagon and insulin. Either or both hormones were then replaced intraportally by continuous infusion as desired. The main observations were as follows. (1) When both hormones were simultaneously replaced for periods up to 4.5h, plasma insulin and glucagon concentrations, total glucose output (glycogenolysis plus gluconeogenesis), glucose utilization and the plasma glucose concentration closely matched the same parameters in 0.9% NaCl-infused controls. (2) When glucagon alone was infused, thereby creating a selective insulin deficiency, glucose output (primarily glycogenolysis) rapidly increased by as much as threefold. Glycogenolytic glucose production then fell off progressively and returned to the control value within 4h. The gluconeogenic conversion of [14C]alanine and [14C]lactate into [14C]glucose was stimulated markedly and increased progressively throughout the test period. Glucagon therefore converted the liver from an organ largely dependent on glycogenolysis for glucose production to one heavily dependent on gluconeogenesis. The potent inhibitory effect of basal insulin on postabsorptive glucose output was also clearly apparent. (3) When insulin alone was infused, thereby creating a selective glucagon deficiency, glucose output (glycogenolysis) fell abruptly by about 30% and remained decreased. Gluconeogenesis also decreased (20%) after the selective removal of both insulin and glucagon, but it only remained suppressed for 1h. The low glucose output led to a modest fall in the blood glucose concentration. Thus glucagon plays an important role in maintaining basal glucose production. (4) When insulin was

  5. Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

    Science.gov (United States)

    Chu, Michael Kok Loon

    Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long

  6. Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity

    DEFF Research Database (Denmark)

    Echwald, Søren Morgenthaler; Bjørbaek, C; Hansen, Torben

    1995-01-01

    Human hexokinase (HK) II, a glucose phosphorylating enzyme in muscle tissue, plays a central role in glucose metabolism. Since reduced insulin-stimulated glucose uptake and reduced glucose-6-phosphate content in muscle have been demonstrated in pre-non-insulin-dependent diabetes mellitus (pre...

  7. Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Holst, Jens J

    2003-01-01

    (HI), 40 mU/m(2) x min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during...... not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes....

  8. Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Hove, Jens D; Freiberg, Jacob

    2002-01-01

    , bicycle exercise test, electrocardiogram and echocardiography were studied [ P(coronary artery disease) ...The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure...... glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity....

  9. Prevalence of impaired glucose tolerance and insulin resistance among obese children and adolescents

    Directory of Open Access Journals (Sweden)

    Robabeh Ghergherechi

    2010-07-01

    Full Text Available Robabeh Ghergherechi1, Ali Tabrizi21Department of Pediatrics Endocrinology, Tabriz University of Medical Sciences, Tabriz, Iran; 2Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, IranPurpose: Obesity is one of the most important nutritional disorders in the world which has an obvious relationship with the incidence of metabolic diseases. Obesity prevalence has increased among children and adolescents during recent decades, leading to a rise in Type 2 diabetes mellitus (DM II prevalence in these two age brackets. Hence, the aim of this study was to assess impaired glucose tolerance and insulin resistance, and gather metabolic findings in obese children and adolescents.Methods and materials: We studied 110 obese children and adolescents (body mass index > 95th percentile for age and gender 4–18 years of age referred to the endocrine clinic of the Children’s Hospital at Tabriz University in a descriptive cross-sectional study. ­Fasting glucose, insulin, and lipid profile in all subjects were determined. Oral glucose tolerance test after eating 75 g/kg glucose was performed. Homeostatic model assessment was used to ­estimate insulin resistance.Results: Impaired glucose tolerance and insulin resistance prevalence in 68 obese adolescents was 14.7% and 31.8%, respectively. Impaired glucose tolerance and insulin resistance was not seen in 23.8% of 42 obese children. No case of DM II was seen. There was a significant statistical difference in glucose (P = 0.003 and insulin (P < 0.001 level at minute 120 in individuals with impaired glucose tolerance compared to obese children and adolescents without impaired glucose tolerance. Rate of insulin resistance in patients with impaired glucose tolerance was greater and had a significant statistical difference (P = 0.03.Conclusion: Obesity has a close relationship with increased risk of impaired glucose tolerance and insulin resistance in children and adolescents. Oral glucose

  10. Dissociation of in vitro sensitivities of glucose transport and antilipolysis to insulin in NIDDM

    International Nuclear Information System (INIS)

    Yki-Jaervinen, H.; Kubo, K.; Zawadzki, J.; Lillioja, S.; Young, A.; Abbott, W.; Foley, J.E.

    1987-01-01

    It is unclear from previous studies whether qualitative or only quantitative differences exist in insulin action in adipocytes obtained from obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) when compared with equally obese nondiabetic subjects. In addition, the role of changes in insulin binding as a cause of insulin resistance in NIDDM is still controversial. The authors compared the sensitivities of [ 14 C]-glucose transport and antilipolysis to insulin and measured [ 125 I]-insulin binding in abdominal adipocytes obtained from 45 obese nondiabetic, obese diabetic, and 15 nonobese female southwestern American Indians. Compared with the nonobese group, the sensitivities of glucose transport antilipolysis were reduced in both the obese nondiabetic and obese diabetic groups. Compared with the obese nondiabetic subjects, the ED 50 for stimulation of glucose transport was higher in the obese patients with NIDDM. In contrast, the ED 50 S for antilipolysis were similar in obese diabetic patients and obese nondiabetic subjects. No differences was found in insulin binding in patients with NIDDM when compared with the equally obese nondiabetic subjects. These data indicate 1) the mechanism of insulin resistance differs in NIDDM and obesity, and 2) the selective loss of insulin sensitivity in NIDDM precludes changes in insulin binding as a cause of insulin resistance in this disorder

  11. What fans the fire: insights into mechanisms of leptin in metabolic syndrome-associated heart diseases.

    Science.gov (United States)

    Dong, Maolong; Ren, Jun

    2014-01-01

    Obesity and metabolic syndrome are one of the most devastating risk factors for cardiovascular diseases. The obesity gene product leptin plays a central role in the regulation of food intake and energy expenditure. The physiological and pathophysiological roles of leptin in cardiovascular system have been investigated extensively since its discovery in 1994. In addition to its well-established metabolic effects, more recent evidence have depicted a rather pivotal role of leptin in inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis and tissue remodeling en route to the pathogenesis of type 2 diabetes mellitus, hypertension, atherosclerosis, and insulin resistance. Under physiological condition, leptin is known to reduce appetite, promote energy expenditure, increase sympathetic activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin may regulate cardiac and vascular function through a nitric oxide-dependent mechanism. However, hyperleptinemia usually occurs with progressively increased body weight and metabolic syndrome development, leading to a state of global or selective leptin resistance. Both central and peripheral leptin resistance may be present under pathophysiological conditions such as inflammation, insulin resistance, hyperlipidemia and a cadre of other cardiovascular diseases including hypertension, atherosclerosis, obesity, ischemic heart disease and heart failure. In this review, we will discuss cardiovascular actions of leptin related to various components of metabolic syndrome. Particular emphasis will be given to insights derived from therapeutic interventions with lifestyle modification, cardiovascular drugs, anti-diabetic and anti-obesity drugs.

  12. Effect of HCV on fasting glucose, fasting insulin and peripheral insulin resistance in first 5 years of infection.

    Science.gov (United States)

    Ahmed, Naeema; Rashid, Amir; Naveed, Abdul Khaliq; Bashir, Qudsia

    2016-02-01

    To assess the effects of hepatitis C virus infection in the first 5 years on fasting glucose, fasting insulin and peripheral insulin resistance. The case-control study was conducted at the Army Medical College, Rawalpindi, from December 2011 to November 2012, and comprised subjects recruited from a government hospital in Rawalpindi. The subjects included known cases of hepatitis C virus infection for at least 5 years, and normal healthy controls. Fasting blood samples of all the subjects were collected and analysed for serum fasting insulin and serum fasting glucose levels. Homeostatic model assessment-Insulin resistance was calculated SPSS 11 was used for statistical analysis. Of the 30 subjects, 20(66.6%) were cases, while 10(33.3%) were controls. Serum fasting glucose mean level in cases was 89.55±9.53 compared to 84.40±9.80 in the controls (p=0.188). The mean serum fasting insulin in controls was 7.52±3.23 and 6.79±3.30 in cases (p=0.567). Homeostatic model assessment-Insulin resistance level in controls was 1.60±0.76 and In the cases it was 1.49±0.74 (p=0.695). Peripheral insulin resistance and development of type 2 diabetes as a complication of hepatitis C virus infection was not likely at least within the first five years of infection.

  13. Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4.

    Science.gov (United States)

    Pearson-Leary, J; Jahagirdar, V; Sage, J; McNay, E C

    2018-02-15

    The insulin-regulated glucose transporter, GluT4, is a key molecule in peripheral insulin signaling. Although GluT4 is abundantly expressed in neurons of specific brain regions such as the hippocampus, the functional role of neuronal GluT4 is unclear. Here, we used pharmacological inhibition of GluT4-mediated glucose uptake to determine whether GluT4 mediates insulin-mediated glucose uptake in the hippocampus. Consistent with previous reports, we found that glucose utilization increased in the dorsal hippocampus of male rats during spontaneous alternation (SA), a hippocampally-mediated spatial working memory task. We previously showed that insulin signaling within the hippocampus is required for processing this task, and that administration of exogenous insulin enhances performance. At baseline levels of hippocampal insulin, inhibition of GluT4-mediated glucose uptake did not affect SA performance. However, inhibition of an upstream regulator of GluT4, Akt, did impair SA performance. Conversely, when a memory-enhancing dose of insulin was delivered to the hippocampus prior to SA-testing, inhibition of GluT4-mediated glucose transport prevented cognitive enhancement. These data suggest that baseline hippocampal cognitive processing does not require functional hippocampal GluT4, but that cognitive enhancement by supra-baseline insulin does. Consistent with these findings, we found that in neuronal cell culture, insulin increases glucose utilization in a GluT4-dependent manner. Collectively, these data demonstrate a key role for GluT4 in transducing the procognitive effects of elevated hippocampal insulin. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The role of insulin, glucagon, dexamethasone, and leptin in the regulation of ketogenesis and glycogen storage in primary cultures of porcine hepatocytes prepared from 60 kg pigs.

    Science.gov (United States)

    Fernández-Fígares, I; Shannon, A E; Wray-Cahen, D; Caperna, T J

    2004-08-01

    A study was conducted to elucidate hormonal control of ketogenesis and glycogen deposition in primary cultures of porcine hepatocytes. Hepatocytes were isolated from pigs (54-68 kg) by collagenase perfusion and seeded into collagen-coated T-25 flasks. Monolayers were established in medium containing fetal bovine serum for 1 day and switched to a serum-free medium for the remainder of the culture period. Hepatocytes were maintained in DMEM/M199 containing 1% DMSO, dexamethasone (10(-6) or 10(-7) M), linoleic acid (3.4 x 10(-5) M), and carnitine (10(-3) M) for 3 days. On the first day of serum-free culture, insulin was added at 1 or 100 ng/ml and glucagon was added at 0, 1, or 100 ng/ml. Recombinant human leptin (200 ng/ml) was added during the final 24 h; medium and all cells were harvested on the third day. Concentrations of acetoacetate and beta-hydroxybutyrate (ketone bodies) in media and glycogen deposition in the cellular compartment were determined. Ketogenesis was highly stimulated by glucagon (1 and 100 ng/ml) and inhibited by insulin. In contrast, glycogen deposition was stimulated by insulin and attenuated by glucagon; high insulin was also associated with a reduction in the ketone body ratio (acetoacetate:beta-hydroxybutyrate). High levels of dexamethasone stimulated ketogenesis, but inhibited glycogen deposition at low insulin. Culture of cells with leptin for 24 h, over the range of insulin, glucagon, and dexamethasone concentrations had no effect on either glycogen deposition or ketogenesis. These data suggest that while adult porcine hepatocytes are indeed sensitive to hormonal manipulation, leptin has no direct influence on hepatic energy metabolism in swine.

  15. Effect of insulin on in vivo glucose utilization in individual tissues of anesthetized lactating rats

    International Nuclear Information System (INIS)

    Burnol, A.F.; Ferre, P.; Leturque, A.; Girard, J.

    1987-01-01

    Glucose utilization rate has been measured in skeletal muscles, white adipose tissue, and mammary gland of anesthetized nonlactating and lactating rats. During lactation, basal [1- 3 H] glucose utilization is decreased by 40% in periovarian white adipose tissue and by 65% in epitrochlearis and extensor digitorum longus but not in soleus muscle. This may be related to the lower blood glucose and plasma insulin concentrations observed during lactation. Basal glucose utilization rate in the mammary gland was, respectively, 18 +/- 2 and 350 +/- 50 μg/min in nonlactating and lactating rats. During the euglycemic hyperinsulinemic clamp, a physiological increment in plasma insulin concentration induces a similar increase in glucose utilization rate in skeletal muscles and white adipose tissue in the two groups of rats. Furthermore this low increase in plasma insulin concentration does not alter mammary glucose utilization rate in nonlactating rats but induces the same increase as a maximal insulin concentration in lactating rats. These data show that the active mammary gland is the most insulin-sensitive tissue of the lactating rat that has been tested. The overall increase in insulin sensitivity and responsiveness that has been described in lactating rats can then mainly be attributed to the presence of the active mammary gland. Plasma insulin was determined by radioimmunoassay

  16. Effect of insulin on in vivo glucose utilization in individual tissues of anesthetized lactating rats

    Energy Technology Data Exchange (ETDEWEB)

    Burnol, A.F.; Ferre, P.; Leturque, A.; Girard, J.

    1987-02-01

    Glucose utilization rate has been measured in skeletal muscles, white adipose tissue, and mammary gland of anesthetized nonlactating and lactating rats. During lactation, basal (1-TH) glucose utilization is decreased by 40% in periovarian white adipose tissue and by 65% in epitrochlearis and extensor digitorum longus but not in soleus muscle. This may be related to the lower blood glucose and plasma insulin concentrations observed during lactation. Basal glucose utilization rate in the mammary gland was, respectively, 18 +/- 2 and 350 +/- 50 g/min in nonlactating and lactating rats. During the euglycemic hyperinsulinemic clamp, a physiological increment in plasma insulin concentration induces a similar increase in glucose utilization rate in skeletal muscles and white adipose tissue in the two groups of rats. Furthermore this low increase in plasma insulin concentration does not alter mammary glucose utilization rate in nonlactating rats but induces the same increase as a maximal insulin concentration in lactating rats. These data show that the active mammary gland is the most insulin-sensitive tissue of the lactating rat that has been tested. The overall increase in insulin sensitivity and responsiveness that has been described in lactating rats can then mainly be attributed to the presence of the active mammary gland. Plasma insulin was determined by radioimmunoassay.

  17. The potential osteogenic effects of systemic lep tin and insulin administration in streptozotocin-induced diabetic female rats

    International Nuclear Information System (INIS)

    Gad, Hayam I.

    2007-01-01

    To evaluate the effect of leptin administration on some biochemical parameters of bone turnover in diabetic rats using either leptin alone or a combination of leptin and insulin. The study was carried out on 32 female Wistar rats supplied by Medical College animal house at King Khalid Hospital, Kingdom of Saudi Arabia during the period from March to December 2006. Rats were divided into 4 groups (8 rats each), controls, non-treated diabetic, leptin-treated diabetic and leptin plus insulin-treated diabetic rats. After induction of diabetes by 6 weeks, treatment with leptin either alone or combined with insulin was continued for 2 weeks more. At the end of treatment, serum samples were taken to measure levels of bone alkaline phosphate (BAP), alkaline phosphates, osteocalcin, insulin like growth factor-1 (IGF-1), parathyroid hormone (PTH), glucose, creatinine, calcium, calcium ions (Ca2+), and phosphorous using enzyme-linked immunoassay (ELISA) and spectrophotometric methods. Body weight and urinary calcium excretion were also measured. Combined leptin and insulin treatment produced a significant increase of serum BAP and a decrease of urinary calcium and serum glucose as compared to rats treated by leptin only, and a significant increase of BAP, alkaline phosphates, IGF-1, and glucose and a decrease in osteocalcin as compared to control rats. Positive correlations were detected between serum IGF-1 levels and each of BAP, alkaline phosphatase and osteocalcin in diabetic rats treated by leptin, and those with leptin plus insulin. Combined leptin plus insulin treatment can offer extra gain of bone formation over leptin treatment alone. Confirmation of these preliminary observations must await careful long-term studies of bone turnover experimental diabetes. (author)

  18. Insulin sensitivity of hepatic glucose and lipid metabolism in animal models of hepatic steatosis

    OpenAIRE

    Grefhorst, Aldo

    2006-01-01

    De lever is betrokken bij de regulatie van zowel het koolhydraat als het vet metabolisme. De lever slaat glucose op als glycogeen, scheidt glucose uit, kan glucose maken uit bijvoorbeeld melkzuur en aminozuren (‘gluconeogenese’), zet glucose om in vet (‘de novo lipogenese’), verbrandt vetzuren in de beta-oxidatie (levert energie voor de gluconeogenese) en scheidt triglycerides uit in de circulatie in ‘very low density lipoprotein’ (VLDL) deeltjes. Insuline remt de glucoseproductie door de lev...

  19. Serum leptin levels in children and adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index

    DEFF Research Database (Denmark)

    Kiess, W; Anil, M; Blum, W F

    1998-01-01

    . It is unclear at present whether this insulin action is a direct or an indirect effect. To investigate whether leptin concentrations in children and adolescents with type 1 diabetes (IDDM) were related to metabolic status, body weight, body mass index and insulin treatment, we have measured leptin...... concentrations in serum from 13 newly diagnosed IDDM patients before the beginning of insulin treatment (8 girls, 5 boys, aged 4.7-17.5 years) and in 134 patients with IDDM during treatment (64 girls, 70 boys, aged 2.6-20.1 years) using a specific radioimmunoassay. The data from patients with diabetes were...... compared with normative data that were derived from a large cohort of healthy children and adolescents. Serum from children with newly diagnosed diabetes had significantly lower levels of leptin (mean 1.28+/-1.60 ng/ml, range 0.14-6.13 ng/ml) compared with healthy children (n=710) (mean 2.2 ng/ml, range 0...

  20. Serum leptin levels in children and adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index

    DEFF Research Database (Denmark)

    Kiess, W; Anil, M; Blum, W F

    1998-01-01

    . It is unclear at present whether this insulin action is a direct or an indirect effect. To investigate whether leptin concentrations in children and adolescents with type 1 diabetes (IDDM) were related to metabolic status, body weight, body mass index and insulin treatment, we have measured leptin...... compared with normative data that were derived from a large cohort of healthy children and adolescents. Serum from children with newly diagnosed diabetes had significantly lower levels of leptin (mean 1.28+/-1.60 ng/ml, range 0.14-6.13 ng/ml) compared with healthy children (n=710) (mean 2.2 ng/ml, range 0...... concentrations in serum from 13 newly diagnosed IDDM patients before the beginning of insulin treatment (8 girls, 5 boys, aged 4.7-17.5 years) and in 134 patients with IDDM during treatment (64 girls, 70 boys, aged 2.6-20.1 years) using a specific radioimmunoassay. The data from patients with diabetes were...

  1. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition.

    Directory of Open Access Journals (Sweden)

    Eduardo R Ropelle

    2010-08-01

    Full Text Available Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKbeta activation and endoplasmic reticulum (ER stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKKbeta/NF-kappaB activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKbeta/NF-kappaB signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKKbeta and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin.

  2. Cold exposure potentiates the effect of insulin on in vivo glucose uptake

    International Nuclear Information System (INIS)

    Vallerand, A.L.; Perusse, F.; Bukowiecki, L.J.

    1987-01-01

    The effects of cold exposure and insulin injection on the rates of net 2-[ 3 H]deoxyglucose uptake (K i ) in peripheral tissues were investigated in warm-acclimated rats. Cold exposure and insulin treatment independently increased K i values in skeletal muscles, heart, white adipose tissue, and brown adipose tissue. The effects of cold exposure were particularly evident in brown adipose tissue where the K i increased >100 times. When the two treatments were combined, it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an insulin-like effect on K i that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from (1) an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and (2) an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake

  3. Cold exposure potentiates the effect of insulin on in vivo glucose uptake

    Energy Technology Data Exchange (ETDEWEB)

    Vallerand, A.L.; Perusse, F.; Bukowiecki, L.J. (Laval Univ. School of Medicine, Quebec (Canada))

    1987-08-01

    The effects of cold exposure and insulin injection on the rates of net 2-({sup 3}H)deoxyglucose uptake (K{sub i}) in peripheral tissues were investigated in warm-acclimated rats. Cold exposure and insulin treatment independently increased K{sub i} values in skeletal muscles, heart, white adipose tissue, and brown adipose tissue. The effects of cold exposure were particularly evident in brown adipose tissue where the K{sub i} increased >100 times. When the two treatments were combined, it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an insulin-like effect on K{sub i} that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from (1) an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and (2) an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake.

  4. Influence of various carbohydrate sources on postprandial glucose, insulin and NEFA concentrations in obese cats.

    Science.gov (United States)

    Mori, A; Ueda, K; Lee, P; Oda, H; Ishioka, K; Sako, T

    2016-01-01

    Carbohydrate is an important source of energy, which can significantly affect postprandial blood glucose and insulin levels in cats. In healthy animals, this is not a big concern; however, in obese and diabetic animals, this is an important detail. In the present study, the impact of four different carbohydrate sources (glucose, maltose, corn starch, and trehalose) on short-term post-prandial serum glucose, insulin, and non-esterified fatty acid (NEFA) concentrations was investigated with four obese cats. Each of the carbohydrate sources was added to a commercial wet food diet for feeding the animals. A significant difference was observed in postprandial glucose, insulin, and NEFA area under the curve (AUC) values between each carbohydrate source in obese cats. Furthermore, glucose and maltose induced the highest postprandial glucose and insulin AUC values, whereas trehalose induced the lowest postprandial glucose and insulin AUC value amongst all carbohydrate sources, respectively, in obese cats. However, trehalose has a higher risk of inducing side effects, such as diarrhea, as compared to other carbohydrate sources. As such, different carbohydrate sources appear to have a very significant impact on post-prandial glycemia and subsequent insulin requirement levels in obese cats. These results might be useful when selecting a prescription diet for obese or diabetic cats. In addition, maltose appears to be capable of inducing experimentally evoked postprandial hyperglycemia in obese cats, which may serve as a good tool for use to check the impact and effectiveness of newly developed oral hypoglycemic drugs or supplements for cats in future experiments.

  5. Dissociation of insulin receptor phosphorylation and stimulation of glucose transport in BC3H-1 myocytes

    International Nuclear Information System (INIS)

    Mojsilovic, L.P.; Standaert, M.L.; Rosic, N.K.; Pollet, R.J.

    1986-01-01

    The authors have investigated insulin receptor phosphorylation in differentiated cultured BC3H-1 myocytes. As for other insulin-responsive cell systems in partially purified wheat germ agglutinin receptor preparations, insulin stimulates the phosphorylation of its own receptor (95K β-subunits) in a dose dependent manner (0-400 nM), as identified by immunoprecipitation with antiinsulin receptor antibodies and SDS-PAGE. In the same preparations they show that 12-0-tetradecanyl phorbol acetate (TPA), which in many respect β-subunits in the same dose dependent manner (0-5 μM). In addition, antiinsulin receptor antibodies (B-10) also induced phosphorylation of mimics insulin action, also induced phosphorylation of the insulin receptor and HPLC tryptic maps of the 32 P-labeled β-subunit were identical to those for insulin-induced receptor phosphorylation. However, while insulin and TPA are potent stimulators of glucose transport in these muscle cells, the antireceptor antibodies alone failed to provoke glucose transport at any concentration. The specificity and activity of these antibodies were confirmed in their system by their ability to inhibit insulin binding and insulin-stimulated glucose transport in a concentration-dependent manner. Their results indicate that phosphorylation of insulin receptor is not a crucial event in mediating insulin action, at least with respect to glucose transport. While the effects of the B-10 antibody in the BC3H-1 myocyte differ from those in the adipocyte, their results provide independent confirmation of their essential conclusion that phosphorylation of the insulin receptor may not be necessary nor sufficient for its acute action in promoting glucose transport

  6. Effects of Everyday Life Events on Glucose, Insulin, and Glucagon Dynamics in Continuous Subcutaneous Insulin Infusion–Treated Type 1 Diabetes: Collection of Clinical Data for Glucose Modeling

    DEFF Research Database (Denmark)

    Schmidt, Signe; Finan, Daniel Aaron; Duun-Henriksen, Anne Katrine

    2012-01-01

    metabolism, we designed and conducted a clinical study.Methods: Patients with insulin pump–treated T1D were recruited to perform everyday life events on two separate days. During the study, patients wore their insulin pumps and, in addition, a continuous glucose monitor and an activity monitor to estimate...... energy expenditure. The sequence of everyday life events was predetermined and included carbohydrate intake, insulin boluses, and bouts of exercise; the events were introduced, temporally separated, in different orders and in different quantities. Throughout the study day, 10-min plasma glucose...... measurements were taken, and samples for plasma insulin and glucagon analyses were obtained every 10 min for the first 30 min after an event and subsequently every 30 min.Results: We included 12 patients with T1D (75% female, 34.3±9.1 years old [mean±SD], hemoglobin A1c 6.7±0.4%). During the 24 study days we...

  7. Sodium-glucose cotransporter-2 inhibition and the insulin: Glucagon ratio: Unexplored dimensions

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available The sodium-glucose cotransporter 2 (SGLT-2 inhibitors are a novel class of glucose-lowering drugs which act by inhibiting the reabsorption of filtered glucose from the kidneys. Their effect on insulin and glucagon levels has recently been studied but is not fully explained. This communication proposes various hypotheses: A direct effect of SGLT-2 inhibition on the alpha cell receptors, a paracrine or intra-islet mediated effect on alpha cell sensitivity to glucose, and a calorie restriction mimetic action, to explain the impact of these drugs on the insulin glucagon ratio.

  8. Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast-acting insulin aspart compared to insulin aspart.

    Science.gov (United States)

    Basu, Ananda; Pieber, Thomas R; Hansen, Ann Kathrine; Sach-Friedl, Stefanie; Erichsen, Lars; Basu, Rita; Haahr, Hanne

    2018-03-01

    Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with accelerated initial absorption after subcutaneous administration, leading to improved postprandial glucose control versus IAsp. We investigated the mechanisms behind the reduced postprandial glucose with faster aspart versus IAsp. In a randomised, double-blind, crossover trial, 41 subjects with type 1 diabetes received identical subcutaneous single faster aspart and IAsp doses (individualised for each subject) together with a standardised mixed meal (including 75 g carbohydrate labelled with [1- 13 C] glucose). Postprandial glucose turnover was determined by the triple-tracer meal method using continuous, variable [6- 3 H] glucose and [6,6- 2 H 2 ] glucose infusion. Insulin exposure within the first hour was 32% greater for faster aspart versus IAsp (treatment ratio faster aspart/IAsp [95% confidence interval] 1.32 [1.18;1.48], pIAsp [95% confidence interval] -0.59 mmol/L [-1.19;0.01], p=0.055). The trend towards reduced ΔPG 1h with faster aspart was due to 12% greater suppression of endogenous glucose production (treatment ratio 1.12 [1.01;1.25], p=0.040) and 23% higher glucose disappearance (1.23 [1.05;1.45], p=0.012) with faster aspart versus IAsp during the first hour. Suppression of free fatty acid levels during the first hour was 36% greater for faster aspart versus IAsp (1.36 [1.01;1.88], 0.042). The trend towards improved postprandial glucose control with faster aspart versus IAsp in this study was due to both greater early suppression of endogenous glucose production and stimulation of glucose disappearance. This article is protected by copyright. All rights reserved.

  9. Analysis of the variation levels of APN, insulin, sensitive C-reactive protein and leptin in the serum of patients with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Du Tongxing; Wang Zizheng; Wang Shukui; Qi Shaokang; Tao Xiaojun

    2005-01-01

    To study the mechanism of pancreatic 13 cell dysfunction and tissue resistance to insulin, and to provide basis for early diagnosis and therapy of the disease, the levels of APN, insulin, sensitive C-reactive protein and leptin in the serum of patients with type 2 diabetes mellitus were determined. Altogether 184 untreatea type 2 diabetes mellitus patients, 30 normal people as the control group, and another 75 type 2 diabetes mellitus patients who have been treated for a year were enrolled in this study. The serum levels of the above indexes were determined by chemiluminescence immunoassay, enzyme immunoassay and radioimmunoassay. The results showed that there were obvious differences in the levels of insulin, leptin, C-reacting protein and insulin antibody between the normal control group and the group of the untreated type 2 diabetes mellitus patients (P<0.01), especially there was significant difference in the level of APN(P<0. 001). Among the 75 type 2 diabetes meltitus patients who have received a year's treatment, all the indexes except for APN and insulin antibody were decreased statistically, while the APN level was increased significantly (P<0.01) than that before the treatment. The determination of markers of type 2 diabetes mellitus is of great significance for its early diagnosis, therapy, prognosis and mechanism research. (authors)

  10. Basal hepatic glucose production is regulated by the portal vein insulin concentration.

    Science.gov (United States)

    Sindelar, D K; Chu, C A; Venson, P; Donahue, E P; Neal, D W; Cherrington, A D

    1998-04-01

    The ability of portal vein insulin to control hepatic glucose production (HGP) is debated. The aim of the present study was to determine, therefore, if the liver can respond to a selective decrease in portal vein insulin. Isotopic ([3H]glucose) and arteriovenous difference methods were used to measure HGP in conscious overnight fasted dogs. A pancreatic clamp (somatostatin plus basal portal insulin and glucagon) was used to control the endocrine pancreas. A 40-min control period was followed by a 180-min test period. During the latter, the portal vein insulin level was selectively decreased while the arterial insulin level was not changed. This was accomplished by stopping the portal insulin infusion and giving insulin peripherally at half the basal portal rate (PID, n=5). In a control group (n=5), the portal insulin infusion was not changed and glucose was infused to match the hyperglycemia that occurred in the PID group. A selective decrease of 120 pmol/l in portal vein insulin was achieved (basal, 150+/-36 to last 30 min, 30+/-12 pmol/l) in the absence of a change in the arterial insulin level (basal, 30+/-3 to last 30 min, 36+/-4 pmol/l). Neither arterial nor portal insulin levels changed in the control group (30+/-6 and 126+/-30 pmol/l, respectively). In response to the selective decrease in portal vein insulin, net hepatic glucose output (NHGO) increased significantly, from 8+/-1 (basal) to 30+/-6 and 14+/-2 micromol x kg(-1) x min(-1) by 15 min and the last 30 min (P glycogenolysis. These studies indicate that after an overnight fast, basal HGP (glycogenolysis) is highly sensitive to the hepatic sinusoidal insulin level.

  11. How swimming affects plasma insulin and glucose concentration in Thoroughbreds: A pilot study.

    Science.gov (United States)

    Bonelli, F; Sgorbini, M; Meucci, V; Sighieri, C; Baragli, P

    2017-08-01

    Low intensity exercise increases insulin-stimulated glucose uptake in skeletal muscle and decreases its plasma concentration. In this study, plasma insulin and glucose concentrations were evaluated 5min before and 5, 15, 25, 35, 45 and 60min after an IV bolus of glucose in 12 Thoroughbreds before and after 1 month of submaximal aquatraining exercise, monitored using heart rate and blood lactate. Plasma glucose concentrations were evaluated using a colorimetric enzymatic method, and plasma insulin concentrations with a solid-phase radioimmunoassay method. Pre-training plasma glucose concentrations at 15, 25 and 35min, area under the glucose curve and peak glucose concentration were significantly higher than post-training values (Pinsulin concentrations were significantly lower than in the post-training period, and plasma insulin was significantly higher at 45 and 60min in the pre-training period than the post-training period. These results indicate that aquatraining could improve insulin-glucose metabolism in horses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

    Science.gov (United States)

    Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

    2016-11-01

    Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Cortisol, insulin, and glucose and the risk of delirium in older adults with hip fracture

    NARCIS (Netherlands)

    Bisschop, Peter H.; de Rooij, Sophia E.; Zwinderman, Aeilko H.; van Oosten, Hannah E.; van Munster, Barbara C.

    2011-01-01

    To determine the relationship between perioperative delirium and cortisol, glucose, and insulin in older adults acutely admitted for hip fracture. Prospective cohort study. Tertiary university center. Consecutive individuals aged 65 and older acutely admitted for hip fracture were invited to

  14. The influence of GLP-1 on glucose-stimulated insulin secretion

    DEFF Research Database (Denmark)

    Kjems, Lise L; Holst, Jens Juul; Vølund, Aage

    2003-01-01

    The intestinally derived hormone glucagon-like peptide 1 (GLP-1) (7-36 amide) has potent effects on glucose-mediated insulin secretion, insulin gene expression, and beta-cell growth and differentiation. It is, therefore, considered a potential therapeutic agent for the treatment of type 2 diabetes....... However, the dose-response relationship between GLP-1 and basal and glucose-stimulated prehepatic insulin secretion rate (ISR) is currently not known. Seven patients with type 2 diabetes and seven matched nondiabetic control subjects were studied. ISR was determined during a graded glucose infusion of 2...... that of the control subjects without GLP-1. Our results show that GLP-1 increases insulin secretion in patients with type 2 diabetes and control subjects in a dose-dependent manner and that the beta-cell responsiveness to glucose may be increased to normal levels with a low dose of GLP-1 infusion. Nevertheless...

  15. Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in type 2 diabetes

    DEFF Research Database (Denmark)

    Staehr, P.; Højlund, K.; Hother-Nielsen, O.

    2003-01-01

    infusion. We assessed whether the choice of either of these methods to obtain euglycaemia biases subsequent assessment of glucose metabolism and insulin action. METHODS: We studied seven obese Type 2 diabetic patients twice: once with (+ ON) and once without (- ON) prior overnight insulin infusion. Glucose...... turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF). RESULTS: Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10.......7 +/- 2.9 mmol/l in the + ON and - ON studies, respectively, and were clamped at -5.5 mmol/l. Basal rates of glucose production (GP) were similar in the + ON and - ON studies, 83 +/- 13 vs. 85 +/- 14 mg m-2 min-1 (NS), whereas basal rates of glucose disappearance (Rd) were lower in the + ON than...

  16. Effects of two commercially available feline diets on glucose and insulin concentrations, insulin sensitivity and energetic efficiency of weight gain.

    Science.gov (United States)

    Coradini, M; Rand, J S; Morton, J M; Rawlings, J M

    2011-10-01

    A low-carbohydrate, high-protein (LCHP) diet is often recommended for the prevention and management of diabetes in cats; however, the effect of macronutrient composition on insulin sensitivity and energetic efficiency for weight gain is not known. The present study compared the effect in adult cats (n 32) of feeding a LCHP (23 and 47 % metabolisable energy (ME)) and a high-carbohydrate, low-protein (HCLP) diet (51 and 21 % ME) on fasting and postprandial glucose and insulin concentrations, and on insulin sensitivity. Tests were done in the 4th week of maintenance feeding and after 8 weeks of ad libitum feeding, when weight gain and energetic efficiency of each diet were also measured. When fed at maintenance energy, the HCLP diet resulted in higher postprandial glucose and insulin concentrations. When fed ad libitum, the LCHP diet resulted in greater weight gain (P cats eating the LCHP diet had similar postprandial glucose concentrations to lean cats eating the HCLP diet. Insulin sensitivity was not different between the diets when cats were lean or overweight, but glucose effectiveness was higher after weight gain in cats fed the HCLP diet. According to the present results, LCHP diets fed at maintenance requirements might benefit cats with multiple risk factors for developing diabetes. However, ad libitum feeding of LCHP diets is not recommended as they have higher energetic efficiency and result in greater weight gain.

  17. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

    OpenAIRE

    Ramnanan, Christopher J.; Saraswathi, Viswanathan; Smith, Marta S.; Donahue, E. Patrick; Farmer, Ben; Farmer, Tiffany D.; Neal, Doss; Williams, Philip E.; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D.; Edgerton, Dale S.

    2011-01-01

    In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic...

  18. The influence of INS VNTR class III allele on auxological parameters, glucose, insulin, lipids, and adipocytokines secretion in prepubertal children born small for gestational age.

    Science.gov (United States)

    Stawerska, Renata; Szałapska, Małgorzata; Borowiec, Maciej; Antosik, Karolina; Młynarski, Wojciech; Lewiński, Andrzej

    2016-01-01

    The insulin gene variable number of tandem repeats (INS VNTR) class III allele has been implicated in lower birth weight, obesity, and insulin resistance. We assessed its influence on birth weight in the Polish population and on the current body mass and metabolic profile in prepubertal children born small for gestational age (SGA). DNA for genotyping of INS VNTR was available for 123 subjects born SGA and 132 born appropriate for gestational age (AGA). We identified two alleles: class I and class III. Next, in 112 prepubertal (aged: 6.8 ± 1.38 years) SGA children, the auxological measurements, fasting serum C-peptide, triglycerides, cholesterol, ghrelin, leptin, adiponectin, resistin, cortisol, and insulin-like growth factor type I (IGF-I) concentrations, as well as glucose and insulin during oral glucose tolerance test (OGTT), were assessed and insulin resistance indices were calculated. The results were analysed depending on INS VNTR variants. The occurrence of individual INS VNTR variants were similar in the SGA and AGA groups. In prepubertal SGA children, we did not observe any statistical differences as regards birth weight, body mass, lipids, or adipocytokine concentrations among I/I, I/III, and III/III class groups. The concentration of insulin in 120' of OGTT was significantly higher in class III homozygous than in class I homozygous individuals. Variant INS VNTR class III was shown not to be associated in any essential way with birth weight in the Polish population. Among prepubertal SGA children, the presence of INS VNTR class III is related to higher insulin secretion during OGTT. (Endokrynol Pol 2016; 67 (6): 585-591).

  19. Blueberries? Impact on Insulin Resistance and Glucose Intolerance

    OpenAIRE

    Stull, April J.

    2016-01-01

    Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM). These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity) after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by hom...

  20. Insulin binding and glucose transport in adipocytes of acarbose-treated Zucker lean and obese rats.

    Science.gov (United States)

    Vasselli, J R; Flory, T; Fried, S K

    1987-01-01

    The intestinal glucosidase inhibitor acarbose was administered as a dietary admix (30 mg/100 g chow diet) to male Zucker obese and lean rats. After 15 weeks, epidiymal fat pads were removed and adipocytes isolated by collagenase digestion. Equilibrium binding of A-14 tyrosine 125I-insulin, and transport of U-14C-glucose was determined was adipocytes incubated for 50 min at 37 degrees C in 0-16000 pM insulin. Insulin binding/cell was enhanced two-fold in lean (P less than 0.01) and obese (n.s.) drug groups. In drug-treated leans, increased sensitivity of glucose transport to submaximally stimulating concentrations of insulin was observed (P less than 0.02). For both genotypes, acarbose mildly decreased insulin levels and body weight gain, although adipocyte size was unaffected. Results indicate that enhanced insulin binding accompanies metabolic improvements induced by acarbose in lean Zucker rats.

  1. Early insulin response and insulin sensitivity are equally important as predictors of glucose tolerance after correction for measurement errors.

    Science.gov (United States)

    Berglund, Lars; Berne, Christian; Svärdsudd, Kurt; Garmo, Hans; Zethelius, Björn

    2009-12-01

    We estimated measurement error (ME) corrected effects of insulin sensitivity (M/I), from euglycaemic insulin clamp, and insulin secretion, measured as early insulin response (EIR) from oral glucose tolerance test (OGTT), on fasting plasma glucose, HbA1c and type 2 diabetes longitudinally and cross-sectional. In a population-based study (n=1128 men) 17 men made replicate measurements to estimate ME at age 71 years. Effect of 1 SD decrease of predictors M/I and EIR on longitudinal response variables fasting plasma glucose (FPG) and HbA1c at follow-ups up to 11 years, were estimated using uncorrected and ME-corrected (with the regression calibration method) regression models. Uncorrected effect on FPG at age 77 years was larger for M/I than for EIR (effect difference 0.10mmol/l, 95% CI 0.00;0.21), while ME-corrected effects were similar (0.02mmol/l, 95% CI -0.13;0.15mmol/l). EIR had greater ME-corrected impact than M/I on HbA1c at age 82 years (-0.11%, -0.28; -0.01%). Due to higher ME effect of EIR on glycaemia is underestimated as compared with M/I. By correcting for ME valid estimates of relative contributions of insulin secretion and insulin sensitivity on glycaemia are obtained.

  2. Effect of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats

    International Nuclear Information System (INIS)

    Anwar, M. K.; Hussain, M. M.; Khan, M. A.; Ahmad, T.

    2013-01-01

    Objective: To compare the effects of combined and individual supplementation of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats. Methods: The randomised controlled trial was conducted at the Department of Physiology, Army Medical College, Rawalpindi, between October 2010 and April 2011. It comprised 80 healthy Sprague Dawley rats who were divided into four groups (n = 20 each). Rats were fed high-fat diet for 2 weeks followed by an intraperitoneal injection of streptozocin to induce type 2 diabetes mellitus. Group I served as diabetic control; group II was given cholecalciferol; group III; levo carnitine; and group IV was administered cholecalciferol and levo carnitine together. After 6 days of supplementation, terminal intracardiac blood extraction was done and samples were analysed for fasting plasma glucose and plasma insulin. Insulin resistance was calculated by homeostatic model assessment for insulin resistance. SPSS 17.0 was used for statistical analysis. Results: Fasting plasma glucose levels were significantly decreased (p <0.001) in the combined supplementation group compared to the diabetic control and individual supplementation groups. Combined supplementation showed a significant increase in fasting plasma insulin levels when compared with diabetic control and levo carnitine groups (p <0.001), and the effect of combined supplementation on ameliorating insulin resistance was significantly better (p <0.001) as compared to the individual supplementation of cholecalciferol and levo carnitine. Conclusions: The combined supplementation of cholecalciferol and levo carnitine for 6 days markedly improved the glycaemic control, insulin secretion and insulin resistance in type 2 diabetic rats on high-fat diet. A prolonged supplementation by both the compounds along with caloric restriction may yield a more promising outcome. (author)

  3. Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

    Science.gov (United States)

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

    2015-04-08

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. Copyright © 2015 the authors 0270-6474/15/355851-09$15.00/0.

  4. Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice.

    Science.gov (United States)

    Rajkumar, K; Krsek, M; Dheen, S T; Murphy, L J

    1996-01-01

    Transgenic mice that overexpressed IGFBP-1 are hyperinsulinemic in the first week of life and gradually develop fasting hyperglycemia. In adult transgenic mice, the hypoglycemic response to IGF-I but not insulin or des (1-3) IGF-I was attenuated (P < 0.05) compared with wild-type mice. Furthermore, in isolated adipocytes from transgenic mice, the stimulatory effect of IGF-I but not insulin on 2-deoxy-[3H]-glucose uptake was reduced (P < 0.02). In contrast, in isolated soleus muscle, the effects of both IGF-I and insulin on 2-deoxy-3H-glucose uptake and on [3H]-glucose incorporation into glycogen were significantly reduced compared to wild-type mice. The decline in specific activity of the 2-deoxy-3H-glucose, a measure of glucose appearance in the circulation, was more marked in transgenic animals (P < 0.05). In addition, tissue uptake of glucose was significantly higher in diaphragm, heart, intestine, liver, soleus muscle, and adipose tissue from fasting transgenic mice. Plasma concentrations of alanine, lysine, and methionine were also elevated in transgenic mice. These data suggest that overexpression of IGFBP-1 attenuates the hypoglycemic effect of endogenous IGF-I, which is initially compensated for by enhanced pancreatic insulin production. However, in adult mice pancreatic insulin content is reduced, insulin resistance is demonstrable in skeletal muscle and fasting hyperglycemia develops. PMID:8878433

  5. Effects of Curcuma longa (turmeric on postprandial plasma glucose and insulin in healthy subjects

    Directory of Open Access Journals (Sweden)

    Ingemansson Sandra

    2010-10-01

    Full Text Available Abstract Background Previous animal studies have shown that Curcuma (C. longa lowers plasma glucose. C. longa may thus be a promising ingredient in functional foods aimed at preventing type 2 diabetes. The purpose of the study is to study the effect of C. longa on postprandial plasma glucose, insulin levels and glycemic index (GI in healthy subjects. Methods Fourteen healthy subjects were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT was administered together with capsules containing a placebo or C. longa. Finger-prick capillary and venous blood samples were collected before, and 15, 30, 45, 60, 90, and 120 min after the start of the OGTT to measure the glucose and insulin levels, respectively. Results The ingestion of 6 g C. longa had no significant effect on the glucose response. The change in insulin was significantly higher 30 min (P = 0.03 and 60 min (P = 0.041 after the OGTT including C. longa. The insulin AUCs were also significantly higher after the ingestion of C. longa, 15 (P = 0.048, 30 (P = 0.035, 90 (P = 0.03, and 120 (P = 0.02 minutes after the OGTT. Conclusions The ingestion of 6 g C. longa increased postprandial serum insulin levels, but did not seem to affect plasma glucose levels or GI, in healthy subjects. The results indicate that C. longa may have an effect on insulin secretion. Trial registration number NCT01029327

  6. Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects.

    Science.gov (United States)

    Wickenberg, Jennie; Ingemansson, Sandra Lindstedt; Hlebowicz, Joanna

    2010-10-12

    Previous animal studies have shown that Curcuma (C.) longa lowers plasma glucose. C. longa may thus be a promising ingredient in functional foods aimed at preventing type 2 diabetes. The purpose of the study is to study the effect of C. longa on postprandial plasma glucose, insulin levels and glycemic index (GI) in healthy subjects. Fourteen healthy subjects were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with capsules containing a placebo or C. longa. Finger-prick capillary and venous blood samples were collected before, and 15, 30, 45, 60, 90, and 120 min after the start of the OGTT to measure the glucose and insulin levels, respectively. The ingestion of 6 g C. longa had no significant effect on the glucose response. The change in insulin was significantly higher 30 min (P = 0.03) and 60 min (P = 0.041) after the OGTT including C. longa. The insulin AUCs were also significantly higher after the ingestion of C. longa, 15 (P = 0.048), 30 (P = 0.035), 90 (P = 0.03), and 120 (P = 0.02) minutes after the OGTT. The ingestion of 6 g C. longa increased postprandial serum insulin levels, but did not seem to affect plasma glucose levels or GI, in healthy subjects. The results indicate that C. longa may have an effect on insulin secretion.

  7. Insulin resistance for glucose metabolism in disused soleus muscle of mice

    Science.gov (United States)

    Seider, M. J.; Nicholson, W. F.; Booth, F. W.

    1981-01-01

    Results of this study on mice provide the first direct evidence of insulin resistance for glucose metabolism in skeletal muscle that has undergone a previous period of reduced muscle usage. This lack of responsiveness to insulin developed in one day and in the presence of hypoinsulinemia. Future studies will utilize the model of hindlimb immobilization to determine the causes of these changes.

  8. Glucose turnover and hormonal changes during insulin-induced hypoglycemia in trained humans

    DEFF Research Database (Denmark)

    Kjær, Michael; Mikines, K J; Christensen, N J

    1984-01-01

    Eight athletes (T), studied the third morning after the last exercise session, and seven sedentary males (C) (maximal O2 consumption 65 +/- 4 vs. 49 +/- 4 (SE) ml X kg-1 X min-1, for T and C men, respectively) had insulin infused until plasma glucose, at an insulin level of 1,600 pmol X l-1, was ...

  9. Oral glucose leads to a differential response in glucose, insulin, and GLP-1 in lean versus obese cats.

    Science.gov (United States)

    Hoenig, M; Jordan, E T; Ferguson, D C; de Vries, F

    2010-02-01

    The response to oral glucose was examined in 10 obese and 9 lean age-matched, neutered cats. In all cats, oral administration of 2g/kg glucose was followed by a prompt increase in glucose, insulin, and glucagon-like peptide (GLP)-1. There were significant differences between lean and obese cats in the areas under the curve for glucose, insulin, and GLP-1. However, the responses were variable, and a clear distinction between individual lean and obese cats was not possible. Therefore, this test cannot be recommended as a routine test to examine insulin resistance in individual cats as it is used in people. A further disadvantage for routine use is also the fact that this test requires gastric tubing for the correct administration of the glucose and associated tranquilization to minimize stress and that it was associated with development of diarrhea in 25% of the cats. GLP-1 concentrations were much lower in obese than lean cats. The low GLP-1 concentrations in obese cats might indicate a contribution of GLP-1 to the lower insulin sensitivity of obese cats, but this hypothesis needs to be further investigated. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Impact of maternal BMI and sampling strategy on the concentration of leptin, insulin, ghrelin and resistin in breast milk across a single feed: a longitudinal cohort study.

    Science.gov (United States)

    Andreas, Nicholas J; Hyde, Matthew J; Herbert, Bronwen R; Jeffries, Suzan; Santhakumaran, Shalini; Mandalia, Sundhiya; Holmes, Elaine; Modi, Neena

    2016-07-07

    We tested the hypothesis that there is a positive association between maternal body mass index (BMI) and the concentration of appetite-regulating hormones leptin, insulin, ghrelin and resistin in breast milk. We also aimed to describe the change in breast milk hormone concentration within each feed, and over time. Mothers were recruited from the postpartum ward at a university hospital in London. Breast milk samples were collected at the participants' homes. We recruited 120 healthy, primiparous, breastfeeding mothers, aged over 18 years. Mothers who smoked, had multiple births or had diabetes were excluded. Foremilk and hindmilk samples were collected from 105 women at 1 week postpartum and 92 women at 3 months postpartum. We recorded maternal and infant anthropometric measurements at each sample collection and measured hormone concentrations using a multiplex assay. The concentration of leptin in foremilk correlated with maternal BMI at the time of sample collection, at 7 days (r=0.31, p=0.02) and 3 months postpartum (r=0.30, p=milk ghrelin and resistin were not correlated with maternal BMI. Ghrelin concentrations at 3 months postpartum were increased in foremilk compared with hindmilk (p=0.01). Concentrations of ghrelin were increased in hindmilk collected at 1  week postpartum compared with samples collected at 3 months postpartum (p=0.03). A trend towards decreased insulin concentrations in hindmilk was noted. Concentrations of leptin and resistin were not seen to alter over a feed. A positive correlation between maternal BMI and foremilk leptin concentration at both time points studied, and foremilk insulin at 3 months postpartum was observed. This may have implications for infant appetite regulation and obesity risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  11. Effect of Human Myotubes-Derived Media on Glucose-Stimulated Insulin Secretion

    Directory of Open Access Journals (Sweden)

    Maria L. Mizgier

    2017-01-01

    Full Text Available Fasting to postprandial transition requires a tight adjustment of insulin secretion to its demand, so tissue (e.g., skeletal muscle glucose supply is assured while hypo-/hyperglycemia are prevented. High muscle glucose disposal after meals is pivotal for adapting to increased glycemia and might drive insulin secretion through muscle-released factors (e.g., myokines. We hypothesized that insulin influences myokine secretion and then increases glucose-stimulated insulin secretion (GSIS. In conditioned media from human myotubes incubated with/without insulin (100 nmol/L for 24 h, myokines were qualitatively and quantitatively characterized using an antibody-based array and ELISA-based technology, respectively. C57BL6/J mice islets and Wistar rat beta cells were incubated for 24 h with control and conditioned media from noninsulin- and insulin-treated myotubes prior to GSIS determination. Conditioned media from insulin-treated versus nontreated myotubes had higher RANTES but lower IL6, IL8, and MCP1 concentration. Qualitative analyses revealed that conditioned media from noninsulin- and insulin-treated myotubes expressed 32 and 23 out of 80 myokines, respectively. Islets incubated with conditioned media from noninsulin-treated myotubes had higher GSIS versus control islets (p<0.05. Meanwhile, conditioned media from insulin-treated myotubes did not influence GSIS. In beta cells, GSIS was similar across conditions. In conclusion, factors being present in noninsulin-stimulated muscle cell-derived media appear to influence GSIS in mice islets.

  12. Indirect Regulation of Endogenous Glucose Production by Insulin: The Single Gateway Hypothesis Revisited.

    Science.gov (United States)

    Bergman, Richard N; Iyer, Malini S

    2017-07-01

    On the basis of studies that investigated the intraportal versus systemic insulin infusion and transendothelial transport of insulin, we proposed the "single gateway hypothesis," which supposes an indirect regulation of hepatic glucose production by insulin; the rate-limiting transport of insulin across the adipose tissue capillaries is responsible for the slow suppression of free fatty acids (FFAs), which in turn is responsible for delayed suppression of hepatic endogenous glucose production (EGP) during insulin infusion. Preventing the fall in plasma FFAs during insulin infusion either by administering intralipids or by inhibiting adipose tissue lipolysis led to failure in EGP suppression, thus supporting our hypothesis. More recently, mice lacking hepatic Foxo1 in addition to Akt1 and Akt2 (L-AktFoxo1TKO), all required for insulin signaling, surprisingly showed normal glycemia. Inhibiting the fall of plasma FFAs in these mice prevented the suppression of EGP during a clamp, reaffirming that the site of insulin action to control EGP is extrahepatic. Measuring whole-body turnover rates of glucose and FFAs in L-AktFoxo1TKO mice also confirmed that hepatic EGP was regulated by insulin-mediated control of FFAs. The knockout mouse model in combination with sophisticated molecular techniques confirmed our physiological findings and the single gateway hypothesis. © 2017 by the American Diabetes Association.

  13. Insulin regulation of renal glucose metabolism in conscious dogs.

    OpenAIRE

    Cersosimo, E; Judd, R L; Miles, J M

    1994-01-01

    Previous studies indicating that postabsorptive renal glucose production is negligible used the net balance technique, which cannot partition simultaneous renal glucose production and glucose uptake. 10 d after surgical placement of sampling catheters in the left renal vein and femoral artery and a nonobstructive infusion catheter in the left renal artery of dogs, systemic and renal glucose and glycerol kinetics were measured with peripheral infusions of [3-3H]glucose and [2-14C]glycerol. Aft...

  14. Significance of determination of female sex hormones (E2, LH, FSH), insulin-like growth factor I (IGF-I) and leptin in girls with precocious puberty

    International Nuclear Information System (INIS)

    Huang Jianrong

    2004-01-01

    Objective: To investigate the diagnostic value of determination of serum levels of estradiol (E 2 ), luteinizing hormone (LH) and follicle stimulating hormone (FSH), insulin-like growth factor (IGF-I) and leptin in girls with idiopathic central precocious puberty (ICPP). Methods: Serum E 2 , LH, FSH, IGF-I (with chemiluminescence immunoassay) and leptin (with RIA) levels were determined in 35 girls with early development of breast as the sign of precocious puberty, of which, 15 was considered to be of the ICPP group and 20 of simple premature thelarche group (SPT). Criteria of diagnosis for ICPP were: peak LH value>12IU/L and LH/FSH>1 after GnRH stimulating test. Results: Serum E 2 , LH, FSH, IGF-I leptin levels in girls with ICPP were significantly higher than those in the girls with SPT (P 0.2 as the cut-off value for diagnosis of ICPP there would still be a positive rate of 86.6% suggesting that the diagnostic criteria might be set lower. Serum IGF-I levels were positively correlated to those of E 2 (r=0.47, P 2 and IGF-I. Conclusion: Determinations of serum E 2 , LH, FHS, IGF-I and leptin levels were helpful for the early diagnosis of ICPP. (author)

  15. Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used

    International Nuclear Information System (INIS)

    Bell, P.M.; Firth, R.G.; Rizza, R.A.

    1986-01-01

    To determine whether [2(3)H], [3(3)H], and [6(14)C]glucose provide an equivalent assessment of glucose turnover in insulin-dependent diabetes mellitus (IDDM) and nondiabetic man, glucose utilization rates were measured using a simultaneous infusion of these isotopes before and during hyperinsulinemic euglycemic clamps. In the nondiabetic subjects, glucose turnover rates determined with [6(14)C]glucose during insulin infusion were lower (P less than 0.02) than those determined with [2(3)H]glucose and higher (P less than 0.01) than those determined with [3(3)H]glucose. In IDDM, glucose turnover rates measured with [6(14)C]glucose during insulin infusion were lower (P less than 0.05) than those determined with [2(3)H]glucose, but were not different from those determined with [3(3)H]glucose. All three isotopes indicated the presence of insulin resistance. However, using [3(3)H]glucose led to the erroneous conclusion that glucose utilization was not significantly decreased at high insulin concentrations in the diabetic patients. [6(14)C] and [3(3)H]glucose but not [2(3)H]glucose indicated impairment in insulin-induced suppression of glucose production. These results indicate that tritiated isotopes do not necessarily equally reflect the pattern of glucose metabolism in diabetic and nondiabetic man

  16. Abnormal transient rise in hepatic glucose production after oral glucose in non-insulin-dependent diabetic subjects.

    Science.gov (United States)

    Thorburn, A; Litchfield, A; Fabris, S; Proietto, J

    1995-05-01

    A transient rise in hepatic glucose production (HGP) after an oral glucosa load has been reported in some insulin-resistant states such as in obese fa/fa Zucker rats. The aim of this study was to determine whether this rise in HGP also occurs in subjects with established non-insulin-dependent diabetes mellitus (NIDDM). Glucose kinetics were measured basally and during a double-label oral glucose tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control' subjects. Twenty minutes after the glucose load, HGP had increased 73% above basal in the NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mumol/kg/min, P < 0.02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) occurred at a similar time. In contrast, the control subjects showed no rise in HGP or plasma glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and control subjects. A 27% increase in the rate of gut-derived glucose absorption was also observed in the NIDDM group, which could be the result of increased gut glucose absorption or decreased first pass extraction of glucose by the liver. Therefore, in agreement with data in animal models of NIDDM, a transient rise in HGP partly contributes to the hyperglycemia observed after an oral glucose load in NIDDM subjects.

  17. Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance.

    Science.gov (United States)

    Hanssen, Mark J W; Wierts, Roel; Hoeks, Joris; Gemmink, Anne; Brans, Boudewijn; Mottaghy, Felix M; Schrauwen, Patrick; van Marken Lichtenbelt, Wouter D

    2015-03-01

    Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation—at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) imaging. We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. www.trialregister.nl NTR3523 FUNDING: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to WDvML) and by the Netherlands Organization for Scientific Research (TOP 91209037 to WDvML).

  18. The lipid accumulation product for the early prediction of gestational insulin resistance and glucose dysregulation.

    Science.gov (United States)

    Brisson, Diane; Perron, Patrice; Kahn, Henry S; Gaudet, Daniel; Bouchard, Luigi

    2013-04-01

    Recent insights linking insulin resistance and lipid overaccumulation suggest a novel approach for the early identification of women who may soon experience glucose dysregulation. Among women without a history of gestational diabetes, we tested the association between the lipid accumulation product (LAP) obtained in early pregnancy and glucose dysregulation or insulin resistance in the second trimester. A total of 180 white pregnant women of French-Canadian origin were included in this study. At 11–14 weeks' gestation, fasting insulin, glucose, C-peptide concentrations, and estimated insulin resistance (HOMA-IR) were obtained. The waist circumference (WC) and fasting triglycerides (TG) were measured to calculate LAP as(WC[cm] - 58) · TG[mmol/L]. At 24–28 weeks' gestation, glucose was measured 2 hours after a 75-g oral glucose challenge and other fasting variables were repeated. Among the nulliparous women tested at the end of the second trimester, fasting insulin, C-peptide, insulin resistance (HOMA-IR index), fasting glucose, and 2-hour glucose progressively increased ( p £ 0.002)according to their first-trimester LAP tertiles. Similar results were observed in parous women except for the glucose variables. The first-trimester LAP tended to show a stronger correlation to the second-trimester HOMAIR index (r = 0.56) than fasting triglyceride levels alone (r = 0.40) or waist circumference alone (r = 0.44) among nulliparous women. Similar associations were observed for parous women. Adjustment for body mass index weakened these associations, especially among parous women. An increased value of LAP at the beginning of a pregnancy could be associated with an increased risk of insulin resistance or hyperglycemia later in gestation.

  19. Effect of glucagon on glucose production during insulin deficiency in the dog.

    Science.gov (United States)

    Cherrington, A D; Lacy, W W; Chiasson, J L

    1978-01-01

    The aim of the present experiments was to determine the effects of basal glucagon on glucose production after induction of prolonged insulin lack in normal conscious dogs fasted overnight. A selective deficiency of insulin or a combined deficiency of both pancreatic hormones was created by infusing somatostatin alone or in combination with an intraportal replacement infusion of glucagon. Glucose production (GP) was measured by a primed constant infusion of [3H-3]glucose, and gluconeogenesis (GNG) was assessed by determining the conversion rate of circulating [14C]alanine and [14C]lactate into [14C]glucose. When insulin deficiency was induced in the presence of basal glucagon the latter hormone caused GP to double and then to decline so that after 4 h it had returned to the conrol rate. The conversion of alanine and lactate into glucose, on the other hand, increased throughout the period of insulin lack. Withdrawal of glucagon after GP had normalized resulted in a 40% fall in GP, a 37% decrease in GNG, and a marked decrease in the plasma glucose concentration. Induction of insulin deficiency in the absence of basal glucagon resulted in an initial (30%) drop in GP followed by a restoration of normal GP after 2--3 h and moderately enhanced glucose formation from alanine and lactate. It can be concluded that (a) the effect of relative hyperglucagonemia on GP is short-lived; (b) the waning of the effect of glucagon is attributable solely to a diminution of glycogenolysis because GNG remains stimulated; (c) basal glucagon markedly enhances the GNG stimulation apparent after induction of insulin deficiency; and (d) basal glucagon worsens the hyperglycemia pursuant on the induction of insulin deficiency both by triggering an initial overproduction of glucose and by maintaining the basal production rate thereafter. PMID:690190

  20. Insulin-stimulated conversion of D-[5-3H] glucose to 3HOH in the perifused isolated rat adipocyte

    International Nuclear Information System (INIS)

    Duckworth, W.C.; Peavy, D.E.; Frechette, P.; Solomon, S.S.

    1986-01-01

    Characteristics of basal and insulin-stimulated glucose utilization by perifused adipocytes have been investigated by measuring the formation of 3 HOH from D-(5- 3 H) glucose. At a glucose concentration of 0.55 mmol/L, basal glucose utilization ranged from 0.5 to 1.0 nmol/min/10(6) cells. Perifused adipocytes showed a maximal response to insulin of a threefold to fourfold increase in the conversion of (5- 3 H) glucose to 3 HOH with a half-maximal response at an insulin concentration of 20 microU/mL. The response to insulin was blocked by phlorizin and cytochalasin B, competitive inhibitors of glucose transport, consistent with an effect of insulin on glucose transport. Insulin increased the Vmax for glucose metabolism but had no effect on the apparent affinity for glucose utilization. The characteristics of glucose utilization and the stimulation of glucose metabolism by insulin in the perifused adipocyte are therefore similar to characteristics previously observed with incubated adipocytes. Because insulin can readily be removed from the system, perifused adipocytes are especially suited for studying the termination of insulin action. The termination of insulin-stimulated glucose metabolism occurred at the same rate in the presence of tracer (1 nmol/L) (5- 3 H)-glucose alone as when 0.55 mmol/L glucose or 2 mmol/L pyruvate were added to the perifusion buffer. The halftime for this process in both cases was approximately 40 minutes. These data suggest that the presence of metabolizable substrate is not required for the termination of the insulin response, but the time course suggests that termination requires more than simply insulin-receptor dissociation

  1. Zinc Status Affects Glucose Homeostasis and Insulin Secretion in Patients with Thalassemia

    Directory of Open Access Journals (Sweden)

    Ellen B. Fung

    2015-06-01

    Full Text Available Up to 20% of adult patients with Thalassemia major (Thal live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05 and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048. Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (−19.0 ± 9.6 μg/dL, showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL and insulin to glucose ratios at 120 min post glucose dose (p = 0.05. Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient.

  2. Insulin-dependent glucose metabolism in dairy cows with variable fat mobilization around calving.

    Science.gov (United States)

    Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Görs, S; Röntgen, M; Sauerwein, H; Bruckmaier, R M; Metges, C C; Kuhla, B; Hammon, H M

    2016-08-01

    Dairy cows undergo significant metabolic and endocrine changes during the transition from pregnancy to lactation, and impaired insulin action influences nutrient partitioning toward the fetus and the mammary gland. Because impaired insulin action during transition is thought to be related to elevated body condition and body fat mobilization, we hypothesized that over-conditioned cows with excessive body fat mobilization around calving may have impaired insulin metabolism compared with cows with low fat mobilization. Nineteen dairy cows were grouped according to their average concentration of total liver fat (LFC) after calving in low [LLFC; LFC 24.4% total fat/DM; n=10) fat-mobilizing cows. Blood samples were taken from wk 7 antepartum (ap) to wk 5 postpartum (pp) to determine plasma concentrations of glucose, insulin, glucagon, and adiponectin. We applied euglycemic-hyperinsulinemic (EGHIC) and hyperglycemic clamps (HGC) in wk 5 ap and wk 3 pp to measure insulin responsiveness in peripheral tissue and pancreatic insulin secretion during the transition period. Before and during the pp EGHIC, [(13)C6] glucose was infused to determine the rate of glucose appearance (GlucRa) and glucose oxidation (GOx). Body condition, back fat thickness, and energy-corrected milk were greater, but energy balance was lower in HLFC than in LLFC. Plasma concentrations of glucose, insulin, glucagon, and adiponectin decreased at calving, and this was followed by an immediate increase of glucagon and adiponectin after calving. Insulin concentrations ap were higher in HLFC than in LLFC cows, but the EGHIC indicated no differences in peripheral insulin responsiveness among cows ap and pp. However, GlucRa and GOx:GlucRa during the pp EGHIC were greater in HLFC than in LLFC cows. During HGC, pancreatic insulin secretion was lower, but the glucose infusion rate was higher pp than ap in both groups. Plasma concentrations of nonesterified fatty acids decreased during HGC and EGHIC, but in both

  3. Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice

    Science.gov (United States)

    The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion. Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia. The physiologically relevant ghrelin receptor is the growth ...

  4. Dual role of the coactivator TORC2 in modulating hepatic glucose output and insulin signaling.

    Science.gov (United States)

    Canettieri, Gianluca; Koo, Seung-Hoi; Berdeaux, Rebecca; Heredia, Jose; Hedrick, Susan; Zhang, Xinmin; Montminy, Marc

    2005-11-01

    Under fasting conditions, the cAMP-responsive CREB coactivator TORC2 promotes glucose homeostasis by stimulating the gluconeogenic program in liver. Following its nuclear translocation in response to elevations in circulating glucagon, TORC2 regulates hepatic gene expression via an association with CREB on relevant promoters. Here, we show that, in parallel with their effects on glucose output, CREB and TORC2 also enhance insulin signaling in liver by stimulating expression of the insulin receptor substrate 2 (IRS2) gene. The induction of hepatic IRS2 during fasting appears critical for glucose homeostasis; knockdown of hepatic IRS2 expression leads to glucose intolerance, whereas hepatic IRS2 overexpression attenuates the gluconeogenic program and reduces fasting glucose levels. By stimulating the expression of IRS2 in conjunction with gluconeogenic genes, the CREB:TORC2 pathway thus triggers a feedback response that limits glucose output from the liver during fasting.

  5. Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus.

    Science.gov (United States)

    Lampman, R M; Schteingart, D E

    1991-06-01

    Exercise training has potential benefits for patients with hyperlipidemia and/or non-insulin dependent diabetes mellitus. In nondiabetic, nonobese subjects with hypertriglyceridemia, exercise training alone increased insulin sensitivity, improved glucose tolerance, and lowered serum triglyceride and cholesterol levels. These improvements did not occur when exercise training alone was given to similar patients with impaired glucose tolerance. In severely obese (X = 125 kg) subjects without diabetes melitus, a 600 calorie diet alone decreased glucose and insulin concentrations and improved glucose tolerance but did not increase insulin sensitivity. The addition of exercise training improved insulin sensitivity. Obese, non-insulin dependent diabetes mellitus subjects on sulfonylurea therapy alone increased insulin levels but failed to improve insulin sensitivity or glucose levels. In contrast, the addition of exercise training to this medication resulted in improved insulin sensitivity and lowered glucose levels. We conclude that exercise training has major effects on lowering triglyceride levels in hyperlipidemic subjects and can potentiate the effect of diet or drug therapy on glucose metabolism in patients with non-insulin dependent diabetes mellitus.

  6. Dual Regulation of Gluconeogenesis by Insulin and Glucose in the Proximal Tubules of the Kidney.

    Science.gov (United States)

    Sasaki, Motohiro; Sasako, Takayoshi; Kubota, Naoto; Sakurai, Yoshitaka; Takamoto, Iseki; Kubota, Tetsuya; Inagi, Reiko; Seki, George; Goto, Moritaka; Ueki, Kohjiro; Nangaku, Masaomi; Jomori, Takahito; Kadowaki, Takashi

    2017-09-01

    Growing attention has been focused on the roles of the proximal tubules (PTs) of the kidney in glucose metabolism, including the mechanism of regulation of gluconeogenesis. In this study, we found that PT-specific insulin receptor substrate 1/2 double-knockout mice, established by using the newly generated sodium-glucose cotransporter 2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance. In contrast, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor. In the HK-2 cells, the gluconeogenic gene expression was suppressed by insulin, accompanied by phosphorylation and inactivation of forkhead box transcription factor 1 (FoxO1). In contrast, glucose deacetylated peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α), a coactivator of FoxO1, via sirtuin 1, suppressing the gluconeogenic gene expression, which was reversed by inhibition of glucose reabsorption. These data suggest that both insulin signaling and glucose reabsorption suppress the gluconeogenic gene expression by inactivation of FoxO1 and PGC1α, respectively, providing insight into novel mechanisms underlying the regulation of gluconeogenesis in the PTs. © 2017 by the American Diabetes Association.

  7. Effects of marine collagen peptides on glucose metabolism and insulin resistance in type 2 diabetic rats.

    Science.gov (United States)

    Zhu, CuiFeng; Zhang, Wei; Mu, Bo; Zhang, Fan; Lai, NanNan; Zhou, JianXin; Xu, AiMin; Liu, JianGuo; Li, Yong

    2017-07-01

    The present study was conducted to investigate the effects of marine collagen peptides (MCPs) on glucose metabolism and insulin resistance using a rat model of type 2 diabetes mellitus (T2DM). Forty T2DM obese Wistar rats were randomly assigned to receive varying doses of MCPs or a vehicle control for 4 weeks. Blood glucose and insulin levels, as well as oxidative stress and inflammation were measured. The expression of glucose transporter type 4 (GLUT4) in skeletal muscles and peroxisome proliferator-activated receptor-α (PPAR-α) in livers of T2DM rats was also measured. It was found that in the group of 9.0 g/kg/day MCPs significantly improved glucose, insulin, and homeostatic model assessment-insulin resistance, and increased the insulin sensitivity index (ISI). In addition, the groups of 4.5 and 2.25 g/kg/day MCPs significantly improved liver steatosis. It was also found that MCPs decreased expression of oxidative stress biomarkers and inflammatory cytokines and adipocytokines in T2DM rats. In conclusion, medium and high doses of MCPs (≥4.5 g/kg/day) improved glucose metabolism and insulin sensitivity in T2DM rats. These beneficial effects of MCPs may be mediated by decreasing oxidative stress and inflammation and by up-regulating GLUT4, and PPAR-α activity.

  8. Alteration of postprandial glucose and insulin concentrations with meal frequency and composition.

    Science.gov (United States)

    Kanaley, Jill A; Heden, Timothy D; Liu, Ying; Fairchild, Timothy J

    2014-11-14

    A frequent eating pattern may alter glycaemic control and augment postprandial insulin concentrations in some individuals due to the truncation of the previous postprandial period by a subsequent meal. The present study examined glucose, insulin, C-peptide and glucose-dependent insulinotropic peptide (GIP) responses in obese individuals when meals were ingested in a high-frequency pattern (every 2 h, 6M) or in a low-frequency pattern (every 4 h, 3M) over 12 h. It also examined these postprandial responses to high-frequency, high-protein meals (6MHP). In total, thirteen obese subjects completed three 12 h study days during which they consumed 6276 kJ (1500 kcal): (1) 3M - 15 % protein and 65 % carbohydrate; (2) 6M - 15 % protein and 65 % carbohydrate; (3) 6MHP - 45 % protein and 35 % carbohydrate. Blood samples were collected every 10 min and analysed for glucose, insulin, C-peptide and GIP. Insulin total AUC (tAUC) and peak insulin concentrations (Pmeal frequency or composition. In obese subjects, ingestion of meals in a low-frequency pattern does not alter glucose tAUC, but increases postprandial insulin responses. The substitution of carbohydrates with protein in a frequent meal pattern results in tighter glycaemic control and reduced postprandial insulin responses.

  9. Psidium guajava Linn. leaf extract affects hepatic glucose transporter-2 to attenuate early onset of insulin resistance consequent to high fructose intake: An experimental study

    Science.gov (United States)

    Mathur, R.; Dutta, Shagun; Velpandian, T.; Mathur, S.R.

    2015-01-01

    Background: Insulin resistance (IR) is amalgam of pathologies like altered glucos metabolism, dyslipidemia, impaired glucose tolerance, non-alcoholic fatty liver disease, and associated with type-II diabetes and cardiometabolic diseases. One of the reasons leading to its increased and early incidence is understood to be a high intake of processed fructose containing foods and beverages by individuals, especially, during critical developmental years. Objective: To investigate the preventive potential of aqueous extract of Psidium guajava leaves (PG) against metabolic pathologies, vis-à-vis, IR, dyslipidemia, hyperleptinemia and hypertension, due to excess fructose intake initiated during developmental years. Materials and Methods: Post-weaning (4 weeks old) male rats were provided fructose (15%) as drinking solution, ad libitum, for 8 weeks and assessed for food and water/fructose intake, body weight, fasting blood sugar, mean arterial pressure, lipid biochemistry, endocrinal (insulin, leptin), histopathological (fatty liver) and immunohistochemical (hepatic glucose transporter [GLUT2]) parameters. Parallel treatment groups were administered PG in doses of 250 and 500 mg/kg/d, po × 8 weeks and assessed for same parameters. Using extensive liquid chromatography-mass spectrometry protocols, PG was analyzed for the presence of phytoconstituents like Myrecetin, Luteolin, Kaempferol and Guavanoic acid and validated to contain Quercetin up to 9.9%w/w. Results: High fructose intake raised circulating levels of insulin and leptin and hepatic GLUT2 expression to promote IR, dyslipidemia, and hypertension that were favorably re-set with PG. Although PG is known for its beneficial role in diabetes mellitus, for the first time we report its potential in the management of lifelong pathologies arising from high fructose intake initiated during developmental years. PMID:25829790

  10. Decreased insulin action on muscle glucose transport after eccentric contractions in rats

    DEFF Research Database (Denmark)

    Asp, S; Richter, Erik

    1996-01-01

    We have recently shown that eccentric contractions (Ecc) of rat calf muscles cause muscle damage and decreased glycogen and glucose transporter GLUT-4 protein content in the white (WG) and red gastrocnemius (RG) but not in the soleus (S) (S. Asp, S. Kristiansen, and E. A. Richter. J. Appl. Physiol....... 79: 1338-1345, 1995). To study whether these changes affect insulin action, hindlimbs were perfused at three different insulin concentrations (0, 200, and 20,000 microU/ml) 2 days after one-legged eccentric contractions of the calf muscles. Compared with control, basal glucose transport was slightly...... velocity of glycogen synthase increased similarly with increasing insulin concentrations in Ecc- and control WG and RG. We conclude that insulin action on glucose transport but not glycogen synthase activity is impaired in perfused muscle exposed to prior eccentric contractions....

  11. Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X

    DEFF Research Database (Denmark)

    Vestergaard, H; Skøtt, P; Steffensen, R

    1995-01-01

    insulin-stimulated glucose disposal to peripheral tissues was lower in patients with MA (13.4 +/- 1.0 v 18.2 +/- 1.4 mg.kg fat-free mass [FFM]-1.min-1, P metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P ...Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study...... was to examine whether patients with MA are insulin-resistant. Nine patients with MA and seven control subjects were studied. All were sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstrated in all MA patients. A euglycemic...

  12. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, B; Larsen, J J; Mikines, K J

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration......-time: T, 44 +/- 9 min (n = 7); S, 102 +/- 23 min (n = 5); P training enhances insulin sensitivity of glucose uptake in subcutaneous adipose tissue and in skeletal muscle. Furthermore, interstitial glycerol data suggest that training also increases insulin sensitivity of lipolysis...

  13. Disassembly of the actin network inhibits insulin-dependent stimulation of glucose transport and prevents recruitment of glucose transporters to the plasma membrane.

    Science.gov (United States)

    Tsakiridis, T; Vranic, M; Klip, A

    1994-11-25

    In muscle and fat tissues, insulin stimulates glucose transport through the translocation of glucose transporter proteins from an intracellular storage pool to the plasma membrane. The mechanism of this translocation is unknown. We have examined the possible role of the actin microfilament network in the stimulation of glucose transport by insulin and on the distribution of glucose transporters, in differentiated L6 rat skeletal muscle cells. Insulin (10(-7) M for 30 min) caused a major reorganization of the actin network of differentiated L6 myotubes. Cytochalasin D, a widely used inhibitor of actin filament formation, caused a dose- and time-dependent disassembly of the actin network, which was associated with an 80% inhibition of the insulin stimulation of glucose transport, without affecting the basal rate of glucose uptake. L6 myotubes express three glucose transporter isoforms, named GLUT1, GLUT3, and GLUT4. Disassembly of the actin network by cytochalasin D did not affect the number of basal glucose transporters in the plasma membrane but reduced the content of all three glucose transporters in intracellular membranes and prevented their appearance at the plasma membrane response to insulin. The inhibitory effect of cytochalasin D treatment on the insulin stimulation of glucose transport occurred downstream of tyrosine phosphorylation of the insulin receptor substrate-1 and of binding of phosphatidylinositol 3-kinase to the insulin receptor substrate-1. Using immunoprecipitation of intact membranes, we detected specific association of the actin-binding protein spectrin with GLUT4 glucose transporter-containing vesicles. We conclude that an intact actin network is required for the correct intracellular localization of glucose transporters, as well as for their incorporation into the plasma membrane in response to insulin. A direct interaction may exist between the actin network and the glucose transporter vesicles which may be mediated through a spectrin

  14. Insulin overlapping in whole blood FTIR spectroscopy in blood glucose measurements

    Science.gov (United States)

    Romo-Cárdenas, G.; Sánchez-López, J. de D.; Luque, P. A.; Cosío-León, M.; Nieto-Hipólito, Juan I.; Vázquez-Briseño, Mabel

    For the last decade, several studies on mid-IR spectroscopy for blood glucose quantification have not considered the compounds involved in the glucose regulation mechanism, in which insulin plays an important role. This work shows how insulin overlaps in the same mid-IR region in which glucose is quantified. This optical absorption interference is an important factor to be considered for this type of studies, in the scope of whole blood modeling for spectroscopy applications and the possible use of computer based metrics.

  15. A novel insulin receptor-binding protein from Momordica charantia enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway.

    Science.gov (United States)

    Lo, Hsin-Yi; Ho, Tin-Yun; Li, Chia-Cheng; Chen, Jaw-Chyun; Liu, Jau-Jin; Hsiang, Chien-Yun

    2014-09-10

    Diabetes, a common metabolic disorder, is characterized by hyperglycemia. Insulin is the principal mediator of glucose homeostasis. In a previous study, we identified a trypsin inhibitor, named Momordica charantia insulin receptor (IR)-binding protein (mcIRBP) in this study, that might interact with IR. The physical and functional interactions between mcIRBP and IR were clearly analyzed in the present study. Photo-cross-linking coupled with mass spectrometry showed that three regions (17-21, 34-40, and 59-66 residues) located on mcIRBP physically interacted with leucine-rich repeat domain and cysteine-rich region of IR. IR-binding assay showed that the binding behavior of mcIRBP and insulin displayed a cooperative manner. After binding to IR, mcIRBP activated the kinase activity of IR by (5.87 ± 0.45)-fold, increased the amount of phospho-IR protein by (1.31 ± 0.03)-fold, affected phosphoinositide-3-kinase/Akt pathways, and consequently stimulated the uptake of glucose in 3T3-L1 cells by (1.36 ± 0.12)-fold. Intraperitoneal injection of 2.5 nmol/kg mcIRBP significantly decreased the blood glucose levels by 20.9 ± 3.2% and 10.8 ± 3.6% in normal and diabetic mice, respectively. Microarray analysis showed that mcIRBP affected genes involved in insulin signaling transduction pathway in mice. In conclusion, our findings suggest that mcIRBP is a novel IRBP that binds to sites different from the insulin-binding sites on IR and stimulates both the glucose uptake in cells and the glucose clearance in mice.

  16. A role for polyamines in glucose-stimulated insulin-gene expression.

    Science.gov (United States)

    Welsh, N

    1990-01-01

    The aim of the present study was to evaluate the possible role for polyamines in the glucose regulation of the metabolism of insulin mRNA of pancreatic islet cells. For this purpose islets were prepared from adult mice and cultured for 2 days in culture medium RPMI 1640 containing 3.3 mM- or 16.7 mM-glucose with or without the addition of the inhibitors of polyamine biosynthesis difluoromethylornithine (DFMO) and ethylglyoxal bis(guanylhydrazone) (EGBG). Culture at the high glucose concentration increased the islet contents of both insulin mRNA and polyamines. The synthesis of total RNA, total islet polyamines and polyamines associated with islet nuclei was also increased. When the combination of DFMO and EGBG was added in the presence of 16.7 mM-glucose, low contents of insulin mRNA, spermine and spermidine were observed. Total islet polyamine synthesis was also depressed by DFMO + EGBG, unlike islet biosynthesis of polyamines associated with nuclei, which was not equally decreased by the polyamine-synthesis inhibitors. Total RNA synthesis and turnover was not affected by DFMO + EGBG. Finally, actinomycin D attenuated the glucose-induced enhancement of insulin mRNA, and cycloheximide counteracted the insulin-mRNA attenuation induced by inhibition of polyamine synthesis. It is concluded that the glucose-induced increase in insulin mRNA is paralleled by increased contents and rates of polyamine biosynthesis and that an attenuation of the increase in polyamines prevents the increase in insulin mRNA. In addition, the results are compatible with the view that polyamines exert their effects on insulin mRNA mainly by increasing the stability of this messenger. PMID:2241922

  17. Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents.

    Science.gov (United States)

    Perry, Rachel J; Cardone, Rebecca L; Petersen, Max C; Zhang, Dongyan; Fouqueray, Pascale; Hallakou-Bozec, Sophie; Bolze, Sébastien; Shulman, Gerald I; Petersen, Kitt Falk; Kibbey, Richard G

    2016-08-01

    Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1-3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the β-cell stimulatory effect of imeglimin is solely or partially responsible for its effects on glycemia remains to be fully confirmed. Here, we show that imeglimin directly activates β-cell insulin secretion in awake rodents without affecting hepatic insulin sensitivity, body composition, or energy expenditure. These data identify a primary amplification rather than trigger the β-cell mechanism that explains the acute, antidiabetic activity of imeglimin. Copyright © 2016 the American Physiological Society.

  18. Interactions of glucagon and free fatty acids with insulin in control of glucose metabolism

    International Nuclear Information System (INIS)

    Chambrier, C.; Picard, S.; Vidal, H.; Cohen, R.; Riou, J.P.; Beylot, M.

    1990-01-01

    To study the interactions of physiological glucagon and free fatty acids (FFA) concentrations with insulin in the control of glucose metabolism, we determined in normal subjects the response of endogenous glucose production (EGP) and glucose utilization (Rd) to a progressive and moderate increase of insulinemia in the presence of glucagon and FFA levels either decreased (somatostatin [SRIF] and insulin infusion, C test) or maintained to normal postabsorptive values isolated (SRIF + insulin + glucagon infusion, G test; SRIF + insulin + Intralipid infusion, IL test) or in association (SRIF + insulin + glucagon + Intralipid infusion, IL + G test). Compared with the C test, maintenance of glucagon level had only small and inconsistent effects on glucose Rd, but induced a shift to the right of the dose-response curve to insulin of EGP (apparent ED50: C test, 10.9 mU.L-1; G test, 15.2 mU.L-1). Intralipid infusion resulted, whether glucagon was substituted or not, in a near total suppression of the insulin-induced increase of glucose Rd (Rd at the end of the tests: C test, 6.13 +/- 0.85 mg.kg-1.min-1; G test, 7.29 +/- 0.87 mg.kg-1.min-1; IL test, 3.30 +/- 0.65 mg.kg-1.min-1; IL + G test, 3.57 +/- 0.42 mg.kg-1.min-1). In the absence of glucagon, substitution Intralipid infusion also antagonized the action of insulin on EGP. However, this effect was no longer apparent when glucagon was replaced (dose-response curve to insulin of EGP during the G and the IL + G test were comparable)

  19. Increased insulin sensitivity and reduced micro and macro vascular disease induced by 2-deoxy-D-glucose during metabolic syndrome in obese JCR: LA-cp rats.

    Science.gov (United States)

    Russell, J C; Proctor, S D

    2007-05-01

    The metabolic syndrome, characterized by obesity, insulin resistance and dyslipidemia, is a major cause of cardiovascular disease. The origins of the syndrome have been hypothesized to lie in continuous availability of energy dense foods in modern societies. In contrast, human physiology has evolved in an environment of sporadic food supply and frequent food deprivation. Intermittent food restriction in rats has previously been shown to lead to reduction of cardiovascular risk and a greater life span. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG) is taken up by cells and induces pharmacological inhibition of metabolism of glucose. We hypothesized that intermittent inhibition of glucose metabolism, a metabolic deprivation, may mimic intermittent food deprivation and ameliorate metabolic and pathophysiological aspects of the metabolic syndrome. Insulin resistant, atherosclerosis-prone JCR:LA-cp rats were treated with 2-DG (0.3% w/w in chow) on an intermittent schedule (2 days treated, one day non-treated, two days treated and two days non-treated) or continuously at a dose to give an equivalent averaged intake. Intermittent 2-DG-treatment improved insulin sensitivity, which correlated with increased adiponectin concentrations. Further, intermittent treatment (but not continuous treatment) reduced plasma levels of leptin and the inflammatory cytokine IL-1 beta. Both 2-DG treatments reduced micro-vascular glomerular sclerosis, but only the intermittent schedule improved macro-vascular dysfunction. Our findings are consistent with reduction in severity of the metabolic syndrome and protection against end stage micro- and macro-vascular disease through intermittent metabolic deprivation at a cellular level by inhibition of glucose oxidation with 2-DG.

  20. Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle

    Science.gov (United States)

    Dupont, Joëlle; Scaramuzzi, Rex J.

    2016-01-01

    Data derived principally from peripheral tissues (fat, muscle and liver) show that insulin signals via diverse interconnecting intracellular pathways and that some of the major intersecting points (known as critical nodes) are the IRSs (insulin receptor substrates), PI3K (phosphoinositide kinase)/Akt and MAPK (mitogen-activated protein kinase). Most of these insulin pathways are probably also active in the ovary and their ability to interact with each other and also with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) signalling pathways enables insulin to exert direct modulating influences on ovarian function. The present paper reviews the intracellular actions of insulin and the uptake of glucose by ovarian tissues (granulosa, theca and oocyte) during the oestrous/menstrual cycle of some rodent, primate and ruminant species. Insulin signals through diverse pathways and these are discussed with specific reference to follicular cell types (granulosa, theca and oocyte). The signalling pathways for FSH in granulosa cells and LH in granulosa and theca cells are summarized. The roles of glucose and of insulin-mediated uptake of glucose in folliculogenesis are discussed. It is suggested that glucose in addition to its well-established role of providing energy for cellular function may also have insulin-mediated signalling functions in ovarian cells, involving AMPK (AMP-dependent protein kinase) and/or hexosamine. Potential interactions of insulin signalling with FSH or LH signalling at critical nodes are identified and the available evidence for such interactions in ovarian cells is discussed. Finally the action of the insulin-sensitizing drugs metformin and the thiazolidinedione rosiglitazone on follicular cells is reviewed. PMID:27234585

  1. Postprandial blood glucose response to a standard test meal in insulin-requiring patients with diabetes treated with insulin lispro mix 50 or human insulin mix 50

    Science.gov (United States)

    Gao, Y; Li, G; Li, Y; Guo, X; Yuan, G; Gong, Q; Yan, L; Zheng, Y; Zhang, J

    2008-01-01

    Aim To compare the 2-h postprandial blood glucose (PPBG) excursion following a standard test meal in insulin-requiring patients with diabetes treated twice daily with human insulin mix 50 vs. insulin lispro mix 50 (LM50). Methods This was a multicentre, randomised, open-label, crossover comparison of two insulin treatments for two 12-week treatment periods in 120 Chinese patients. One- and 2-h PPBG and excursion values were obtained following a standardised test meal. Fasting blood glucose (FBG), haemoglobin A1c (HbA1c), insulin dose, rate of hypoglycaemia and safety data were obtained. A crossover analysis using SAS Proc MIXED was employed. Results Mean 2-h PPBG excursion decreased from 6.32 ± 3.07 mmol/l at baseline to 3.47 ± 2.97 mmol/l at end-point in the LM50 group, and from 6.31 ± 2.88 at baseline to 5.02 ± 3.32 mmol/l at end-point in the human insulin mix 50 group (p < 0.001). Two-hour PPBG (p = 0.004) and 1-h PPBG excursion (p < 0.001) were significantly lower with LM50 as compared with human insulin mix 50. Both treatment groups were equivalent for HbA1c control, 1-h PPBG and insulin dose requirements. Mean FBG was higher with LM50 than with human insulin mix 50 (p = 0.023). The overall incidence of treatment-emergent adverse events and hypoglycaemia rate per 30 days were similar between treatment groups. Conclusions Insulin lispro mix 50 provided better postprandial glycaemic control compared with human insulin mix 50 while providing the convenience of injecting immediately before meals. Both treatments were generally well tolerated by all randomly assigned patients. PMID:18657196

  2. Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic β-cells

    Directory of Open Access Journals (Sweden)

    Muto Takashi

    2011-04-01

    Full Text Available Abstract Background Glycated albumin (GA is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic β cells. Methods Islets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA and GA was measured under three different glucose concentrations, 3 mM (G3, 7 mM (G7, and 15 mM (G15, with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS, and the expression of iNOS-mRNA was investigated by real-time PCR. Results Insulin secretion in the presence of HA and GA was 20.9 ± 3.9 and 21.6 ± 5.5 μU/3 islets/h for G3 (P = 0.920, and 154 ± 9.3 and 126.1 ± 7.3 μU/3 islets/h (P = 0.046, for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion. Conclusion GA suppresses glucose-induced insulin secretion from rat pancreatic β-cells through impairment of intracellular glucose metabolism.

  3. Glucose effectiveness and insulin sensitivity measurements derived from the non-insulin-assisted minimal model and the clamp techniques are concordant

    DEFF Research Database (Denmark)

    Henriksen, Jan Erik; Alford, Frank; Ward, Glenn

    2010-01-01

    We investigated the concordance between glucose effectiveness (SG) and insulin sensitivity (SI), derived from the unmodified dynamic non-insulin-assisted intravenous glucose tolerance test (IVGTT) implemented by SG(MM) and SI(MM); simulation analysis and modelling/conversational interaction (SAAM....../CONSAM) versus the eu/hyperglycaemic basal insulinaemic and the euglycaemic hyperinsulinaemic clamp (SG(CLAMP) and SI(CLAMP))....

  4. Glargine and protamine zinc insulin have a longer duration of action and result in lower mean daily glucose concentrations than lente insulin in healthy cats.

    Science.gov (United States)

    Marshall, R D; Rand, J S; Morton, J M

    2008-06-01

    The pharmacological effects of glargine, protamine zinc (PZI), and lente insulins were evaluated in nine healthy cats. A 3-way crossover study was performed and plasma concentrations of insulin and glucose were determined for 24 h after a single subcutaneous injection of each insulin at 3-day intervals. Time to onset of action did not differ between insulins. Mean time to first nadir glucose was longer for glargine (14 h) relative to PZI (4 h) and lente (5 h). PZI was biphasic in action with nadirs at 4 and 14 h with the second nadir occurring at a similar time to glargine. Nadir glucose did not differ significantly between insulin types. The duration of action was similar for glargine and PZI and was longer than that for lente insulin. Mean daily glucose after glargine and PZI were also similar and were lower than after lente insulin. Time to reach peak insulin did not differ between insulin types. Time to return to baseline insulin level for PZI was longer than glargine but did not differ significantly from lente. In conclusion, healthy cats injected subcutaneously with glargine, compared to those injected with lente insulin, have a later glucose nadir and longer duration of action. Glargine and PZI had similar durations of action in study cats but a larger study is required to obtain precise comparisons of duration of action.

  5. Differentiation of the insulin-sensitive glucose transporter in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Frost, S.C.; Baly, D.L.; Cushman, S.W.; Lane, M.D.; Simpson, I.A.

    1986-01-01

    3T3-L1 fibroblasts differentiate in culture to resemble adipocytes both morphologically and biochemically. Insulin-sensitive glucose transport, as measured by 2-deoxy-[1- 14 C]- glucose uptake in the undifferentiated cell is small (2X). In contrast, the rate of glucose transport in fully differentiated cells is elevated 15-fold over basal in the presence of insulin. To determine if this is due to an increase in the number of transporters/cell or accessibility to the transporters, the number of transporters was measured in subcellular fractions over differentiation using a 3 H-cytochalasin B binding assay. The increase in the rate of insulin-sensitive glucose transport directly parallels an increase in the number of transporters which reside in an insulin-responsive intracellular compartment. This observation was confirmed by identifying the transporters by immunoblotting using an antibody generated against the human erythrocyte transporter. The molecular weight of this transporter increases over differentiation from a single band of 40kDa to a heterogeneous triplet of 40, 44 and 48kDa. These data suggest that the transporter undergoes differential processing and that the functional, insulin-responsive transporter may be different from the insulin-insensitive (basal) transporter

  6. Potent humanin analog increases glucose-stimulated insulin secretion through enhanced metabolism in the β cell.

    Science.gov (United States)

    Kuliawat, Regina; Klein, Laura; Gong, Zhenwei; Nicoletta-Gentile, Marianna; Nemkal, Anjana; Cui, Lingguang; Bastie, Claire; Su, Kai; Huffman, Derek; Surana, Manju; Barzilai, Nir; Fleischer, Norman; Muzumdar, Radhika

    2013-12-01

    Humanin (HN) is a 24-aa polypeptide that offers protection from Alzheimer's disease and myocardial infarction, increases insulin sensitivity, improves survival of β cells, and delays onset of diabetes. Here we examined the acute effects of HN on insulin secretion and potential mechanisms through which they are mediated. Effects of a potent HN analog, HNGF6A, on glucose-stimulated insulin secretion (GSIS) were assessed in vivo and in isolated pancreatic islets and cultured murine β cell line (βTC3) in vitro. Sprague-Dawley rats (3 mo old) that received HNGF6A required a significantly higher glucose infusion rate and demonstrated higher insulin levels during hyperglycemic clamps compared to saline controls. In vitro, compared to scrambled peptide controls, HNGF6A increased GSIS in isolated islets from both normal and diabetic mice as well as in βTC3 cells. Effects of HNGF6A on GSIS were dose dependent, K-ATP channel independent, and associated with enhanced glucose metabolism. These findings demonstrate that HNGF6A increases GSIS in whole animals, from isolated islets and from cells in culture, which suggests a direct effect on the β cell. The glucose-dependent effects on insulin secretion along with the established effects on insulin action suggest potential for HN and its analogs in the treatment of diabetes.

  7. Adenovirus infection results in alterations of insulin signaling and glucose homeostasis

    Science.gov (United States)

    Jiang, Shaoning; Gavrikova, Tatyana A.; Pereboev, Alexander

    2010-01-01

    Recombinant adenovirus (Ad) vectors can initiate an inflammatory response, limiting its use in gene therapy and basic research. Despite increased efforts to better understand Ad infection, little is known about how it affects cellular metabolic responses. In the current studies, we explored the effects of Ad vectors on insulin signaling molecules and glucose homeostasis. Nonreplicative Ad vectors were injected into rats through the tail vein, and at 4–13 days postinjection insulin signaling and glucose tolerance were examined. Ad vector infection significantly reduced total levels of the insulin receptor (IR), and insulin receptor substrates 1 and 2 (IRS-1, IRS-2) in the liver of rats, resulting in decreased insulin-induced tyrosine phosphorylation of IR, IRS-1, and IRS-2, and decreased interaction of IRS-1 and IRS-2 with phosphoinositide 3-kinase (PI3K). In addition, Ad infection resulted in impaired systemic glucose homeostasis, which recovered by 13 days, after the protein levels of IR, IRS-1, and IRS-2 had started to normalize. Expression of a TNF inhibitor or Kupffer cell depletion attenuated the Ad vector-induced decreases of insulin signaling molecules, indicating a potential role of Kupffer cell activation in this process. These studies provide evidence that systemic administration of Ad vectors can impair insulin signaling in liver, resulting in altered systemic glucose metabolism. Thus, effects of Ad vector infection on insulin action and glucose metabolism need to be considered when Ad vectors are used in research or gene therapy and may be more broadly applicable to other viral agents. PMID:20388825

  8. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

    Science.gov (United States)

    Ramnanan, Christopher J.; Saraswathi, Viswanathan; Smith, Marta S.; Donahue, E. Patrick; Farmer, Ben; Farmer, Tiffany D.; Neal, Doss; Williams, Philip E.; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D.; Edgerton, Dale S.

    2011-01-01

    In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP. PMID:21865644

  9. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs.

    Science.gov (United States)

    Ramnanan, Christopher J; Saraswathi, Viswanathan; Smith, Marta S; Donahue, E Patrick; Farmer, Ben; Farmer, Tiffany D; Neal, Doss; Williams, Philip E; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D; Edgerton, Dale S

    2011-09-01

    In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP.

  10. Insulin-coated gold nanoparticles as a new concept for personalized and adjustable glucose regulation

    Science.gov (United States)

    Shilo, Malka; Berenstein, Peter; Dreifuss, Tamar; Nash, Yuval; Goldsmith, Guy; Kazimirsky, Gila; Motiei, Menachem; Frenkel, Dan; Brodie, Chaya; Popovtzer, Rachela

    2015-12-01

    Diabetes mellitus is a chronic metabolic disease, characterized by high blood glucose levels, affecting millions of people around the world. Currently, the main treatment for diabetes requires multiple daily injections of insulin and self-monitoring of blood glucose levels, which markedly affect patients' quality of life. In this study we present a novel strategy for controlled and prolonged glucose regulation, based on the administration of insulin-coated gold nanoparticles (INS-GNPs). We show that both intravenous and subcutaneous injection of INS-GNPs into a mouse model of type 1 diabetes decreases blood glucose levels for periods over 3 times longer than free insulin. We further showed that conjugation of insulin to GNPs prevented its rapid degradation by the insulin-degrading-enzyme, and thus allows controlled and adjustable bio-activity. Moreover, we assessed different sizes and concentrations of INS-GNPs, and found that both parameters have a critical effect in vivo, enabling specific adjustment of blood glucose levels. These findings have the potential to improve patient compliance in diabetes mellitus.

  11. [Adiponectin, insulin and glucose concentrations in overweight and obese subjects after a complex carbohydrates (fiber) diet].

    Science.gov (United States)

    González Rodríguez, Dora Cristina; Solano R, Liseti; González Martínez, Julio César

    2009-09-01

    Adiponectin one of the cytokines secreted by the adipose tissue that regulates the energetic metabolism through glucose and insulin interactions, stimulates the oxidation of fatty acids, reduces the plasmatic triglycerides and improves glucose metabolism by increasing insulin sensibility. Serum concentrations of adiponectin, insulin and glucose were assessed in order to establish association to weight loss after a dietary regime based on consumption of complex carbohydrates (fiber) during six weeks. Overweight and obese subjects (n=56) were studied by anthropometry. Adiponectin and insulin were measured by ELISA and glucose by Colorimetry. Data was analyzed by non parametric tests to compare independent or related samples. 12 men and 44 women, aged 20 to 55 years, 17 overweight and 39 obese were assessed. Adiponectin concentration was significantly low at basal determination in all the subjects (4,47 +/- 1,64); being higher in women (4,62 +/- 1,57 vs 3,93 +/- 1,86 microU/mL in men), while glucose and insulin values were at normal range (82,46 +/-26,51 mg/dL and 14,12 +/- 10,15 microU/mL) respectively with no significant differences for sex. Overweight subjects had significantly higher adiponectin concentrations than obese participants, at all measurements. Dietary regime promoted significant increase in adiponectin concentration at second and sixth week, with a negative correlation to body mass index and gender as they lost body weight.

  12. Peripheral effects of insulin dominate suppression of fasting hepatic glucose production

    International Nuclear Information System (INIS)

    Ader, M.; Bergman, R.N.

    1990-01-01

    Insulin may suppress hepatic glucose production directly, or indirectly via suppression of release of gluconeogenic substrates from extrasplanchnic tissues. To compare these mechanisms, we performed insulin dose-response experiments in conscious dogs at euglycemia, during somatostatin infusion, and intraportal glucagon replacement. Insulin was sequentially infused either intraportally (0.05, 0.20, 0.40, 1.0, 1.4, and/or 3.0; protocol I) or systemically at half the intraportal rate (0.025, 0.10, 0.20, 0.50, 0.70, and/or 1.5 mU.min-1.kg-1; protocol II). Exogenous glucose infused during clamps was labeled with 3-[3H]glucose (2 microCi/g) to prevent a fall in plasma specific activity (P greater than 0.2) that may have contributed to previous underestimations of hepatic glucose output (HGO). Portal insulins were up to threefold higher during intraportal infusion, but peripheral insulin levels were not different between the intraportal and systemic protocols [7 +/- 5 vs. 9 +/- 1, 12 +/- 4 vs. 13 +/- 6, 16 +/- 3 vs. 27 +/- 5, 70 +/- 23 vs. 48 +/- 8, 83 +/- 3 vs. 86 +/- 21, and 128 vs. 120 +/- 14 microU/ml for paired insulin doses; P greater than 0.06 by analysis of variance (ANOVA)]. Despite higher portal insulin levels in protocol I, HGO suppression was equivalent in the two protocols when systemic insulin was matched, from 3.3 +/- 0.1 to near-total suppression at 0.3 mg.min-1.kg-1 at the highest insulin infusion rate (3.0 mU.min-1.kg-1; P less than 0.0001) with intraportal insulin, from 2.9 +/- 0.8 to -0.8 +/- 0.2 mg.min-1.kg-1 in protocol II (P less than 0.001). Suppression of HGO was similar at matched systemic insulin, regardless of portal insulin, suggesting the primacy of insulin's action on the periphery in its restraint of hepatic glucose production

  13. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity

    Science.gov (United States)

    Shaham, Oded; Wei, Ru; Wang, Thomas J; Ricciardi, Catherine; Lewis, Gregory D; Vasan, Ramachandran S; Carr, Steven A; Thadhani, Ravi; Gerszten, Robert E; Mootha, Vamsi K

    2008-01-01

    Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy. PMID:18682704

  14. Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity.

    Science.gov (United States)

    Linder, Katarzyna; Schleger, Franziska; Ketterer, Caroline; Fritsche, Louise; Kiefer-Schmidt, Isabelle; Hennige, Anita; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas

    2014-06-01

    Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity. Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined. Maternal insulin increased from a fasting level of 67 ± 25 pmol/l (mean ± SD) to 918 ± 492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4 ± 0.3 to 7.4 ± 1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297 ± 99 to 235 ± 84 ms (p = 0.01) and then remained stable until 120 min (235 ± 84 vs 251 ± 91 ms, p = 0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283 ± 79 ms) than those of insulin-sensitive mothers (178 ± 46 ms, p = 0.03). Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.

  15. Racl Signaling Is Required for Insulin-Stimulated Glucose Uptake and Is Dysregulated in Insulin-Resistant Murine and Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Sylow, L.; Jensen, T. E.; Kleinert, M.

    2013-01-01

    The actin cytoskeleton-regulating GTPase Racl is required for insulin-stimulated GLUT4 translocation in cultured muscle cells. However, involvement of Racl and its downstream signaling in glucose transport in insulin-sensitive and insulin-resistant mature skeletal muscle has not previously been i...

  16. Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.

    Science.gov (United States)

    Tuulari, Jetro J; Karlsson, Henry K; Hirvonen, Jussi; Hannukainen, Jarna C; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

    2013-08-01

    Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

  17. Effect of Chlorogenic Acid Administration on Glycemic Control, Insulin Secretion, and Insulin Sensitivity in Patients with Impaired Glucose Tolerance.

    Science.gov (United States)

    Zuñiga, Laura Y; Aceves-de la Mora, Martha C Aceves-de; González-Ortiz, Manuel; Ramos-Núñez, Julia L; Martínez-Abundis, Esperanza

    2017-12-20

    Chlorogenic acid has been described as a novel polyphenol with metabolic effects on glucose homeostasis. The aim of this study was to evaluate the effect of chlorogenic acid administration on glycemic control, insulin secretion, and insulin sensitivity in patients with impaired glucose tolerance (IGT). A randomized, double-blind, placebo-controlled clinical trial was performed in 30 patients with IGT; 15 patients randomly assigned to oral chlorogenic acid received 400 mg three times per day for 12 weeks, and the other 15 patients received placebo in the same way. Before and after the intervention, anthropometric and metabolic measurements, including fasting plasma glucose (FPG), glycated hemoglobin A1c, and a lipid profile, were performed. Area under the curve of glucose and insulin as well as the insulinogenic, Stumvoll, and Matsuda indices were calculated. Wilcoxon, Mann-Whitney U, and chi-square tests were performed, and P ≤ .05 was considered statistically significant. There were significant decreases in FPG (5.7 ± 0.4 vs. 5.5 ± 0.4 mmol/L, P = .002), insulinogenic index (0.71 ± 0.25 vs. 0.63 ± 0.25, P = .028), body weight, body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein levels in the chlorogenic acid group, with an increment in the Matsuda index (1.98 ± 0.88 vs. 2.30 ± 1.23, P = .002). There were no significant differences in the placebo group. In conclusion, chlorogenic acid administration in patients with IGT decreased FPG and insulin secretion, while increasing insulin sensitivity and improving both anthropometric evaluations and the lipid profile.

  18. Mathematical model of the glucose-insulin regulatory system: From the bursting electrical activity in pancreatic β-cells to the glucose dynamics in the whole body

    Science.gov (United States)

    Han, Kyungreem; Kang, Hyuk; Choi, M. Y.; Kim, Jinwoong; Lee, Myung-Shik

    2012-10-01

    A theoretical approach to the glucose-insulin regulatory system is presented. By means of integrated mathematical modeling and extensive numerical simulations, we probe the cell-level dynamics of the membrane potential, intracellular Ca2+ concentration, and insulin secretion in pancreatic β-cells, together with the whole-body level glucose-insulin dynamics in the liver, brain, muscle, and adipose tissues. In particular, the three oscillatory modes of insulin secretion are reproduced successfully. Such comprehensive mathematical modeling may provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination.

  19. Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle

    Science.gov (United States)

    Henriksen, Erik J.; Tischler, Marc E.; Johnson, David G.

    1986-01-01

    Hind leg muscles of female rats were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D(U-C-14) glucose, release of lactate and pyruvate, incorporation of D-(U-C-14) glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-(1,2-H-3) glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased, by 50 percent the concentration of insuling receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

  20. Use of Modified Glucose-Insulin-Potassium Mixture in Cardiosurgical Patients

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2006-01-01

    Full Text Available The investigation was undertaken to study the hemodynamic and metabolic effects of modified (with elevated glucose and insulin levels glucose-insulin-potassium (GIP mixture in the correction of acute heart failure in cardiosurgical patients. After infusion of the modified GIP mixture (0.9 g of glucose per kg body weight and 3.75 units of insulin per g glucose, in 15 patients (12 males and 3 females aged 35 to 72 (54±5 years the increase (p<0.05 in cardiac index and stroke volume index was 21% with simultaneous 20 and 17% decreases in pulmonary wedge pressure and mean pulmonary pressure, respectively (p<0.05. The duration of infusion was 5 hours. A steady-state improvement of cardiac pump function and metabolic parameters could reduce the dosage of cardiotonic drugs 12 hours after administration of the modified GIP mixture. During and after administration of the mixture, the blood levels of glucose and potassium were substantially unchanged. In the study group, all the patients survived. The duration of a resuscitative period was 2.4±0.2 days. With the management protocol used, infusion of the modified GIP mixture was favorable to the steady-state improvement of cardiac pump function without carbohydrate and electrolyte homeostatic impairments.acute heart failure; glucose-insulin-potassium mixture

  1. Cocoa flavonoids attenuate high glucose-induced insulin signalling blockade and modulate glucose uptake and production in human HepG2 cells.

    Science.gov (United States)

    Cordero-Herrera, Isabel; Martín, María Ángeles; Goya, Luis; Ramos, Sonia

    2014-02-01

    Insulin resistance is the primary characteristic of type 2 diabetes. Cocoa and its main flavanol, (-)-epicatechin (EC), display some antidiabetic effects, but the mechanisms for their preventive activities related to glucose metabolism and insulin signalling in the liver remain largely unknown. In the present work, the preventive effect of EC and a cocoa polyphenolic extract (CPE) on insulin signalling and on both glucose production and uptake are studied in insulin-responsive human HepG2 cells treated with high glucose. Pre-treatment of cells with EC or CPE reverted decreased tyrosine-phosphorylated and total levels of IR, IRS-1 and -2 triggered by high glucose. EC and CPE pre-treatment also prevented the inactivation of the PI3K/AKT pathway and AMPK, as well as the diminution of GLUT-2 levels induced by high glucose. Furthermore, pre-treatment of cells with EC and CPE avoided the increase in PEPCK levels and the diminished glucose uptake provoked by high glucose, returning enhanced levels of glucose production and decreased glycogen content to control values. These findings suggest that EC and CPE improved insulin sensitivity of HepG2 treated with high glucose, preventing or delaying a potential hepatic dysfunction through the attenuation of the insulin signalling blockade and the modulation of glucose uptake and production. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. α-Mangostin Improves Glucose Uptake and Inhibits Adipocytes Differentiation in 3T3-L1 Cells via PPARγ, GLUT4, and Leptin Expressions

    Directory of Open Access Journals (Sweden)

    Muhammad Taher

    2015-01-01

    Full Text Available Obesity has been often associated with the occurrence of cardiovascular diseases, type 2 diabetes, and cancer. The development of obesity is also accompanied by significant differentiation of preadipocytes into adipocytes. In this study, we investigated the activity of α-mangostin, a major xanthone component isolated from the stem bark of G. malaccensis, on glucose uptake and adipocyte differentiation of 3T3-L1 cells focusing on PPARγ, GLUT4, and leptin expressions. α-Mangostin was found to inhibit cytoplasmic lipid accumulation and adipogenic differentiation. Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells. Analyses of 2-deoxy-D-[3H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P<0.05 with highest activity found at 25 μM. In addition, α-mangostin increased the amount of free fatty acids (FFA released. The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression. Induction of glucose uptake and free fatty acid release by α-mangostin were accompanied by increasing mRNA expression of GLUT4 and leptin. These evidences propose that α-mangostin might be possible candidate for the effective management of obesity in future.

  3. Lifespan and Glucose Metabolism in Insulin Receptor Mutant Mice

    Directory of Open Access Journals (Sweden)

    Takahiko Shimizu

    2011-01-01

    Full Text Available Insulin/insulin-like growth factor type 1 signaling regulates lifespan and resistance to oxidative stress in worms, flies, and mammals. In a previous study, we revealed that insulin receptor (IR mutant mice, which carry a homologous mutation found in the long-lived daf-2 mutant of Caenorhabditis elegans, showed enhanced resistance to oxidative stress cooperatively modulated by sex hormones and dietary signals (Baba et al., (2005. We herein investigated the lifespan of IR mutant mice to evaluate the biological significance of insulin signaling in mice. Under normoxia, mutant male mice had a lifespan comparable to that of wild-type male mice. IR mutant female mice also showed a lifespan similar to that of wild-type female mice, in spite of the fact that the IR mutant female mice acquired more resistance to oxidative stress than IR mutant male mice. On the other hand, IR mutant male and female mice both showed insulin resistance with hyperinsulinemia, but they did not develop hyperglycemia throughout their entire lifespan. These data indicate that the IR mutation does not impact the lifespan in mice, thus suggesting that insulin signaling might have a limited effect on the lifespan of mice.

  4. A study of the effect of aging on insulin and glucagon release during intravenous glucose tolerance tests

    International Nuclear Information System (INIS)

    Hafiez, A.A.; El-Kirdassy, Z.; Abdel-Hafez, M.A.; Megahed, G.; Ashmawy, K.R.; Ziada, A.; Sheba, E.

    1985-01-01

    Glucose intolerance in aged persons had been reported by many investigators. In this study intravenous glucose tolerance tests have been performed of 63 subjects classified into three groups (20 - 40 years, 40 - 60 years and above 60 years). With increasing age, significant increases of plasma glucose and insulin and decreases in glucose assimilation, insulin stimulating activity and insulin index were observed. No significant differences have been found in plasma glucagon levels of glucagon suppression areas so that it may be concluded that glucagon is of no importance to the reduction of glucose tolerance with aging. (author)

  5. Role of Akt substrate of 160 kDa in insulin-stimulated and contraction-stimulated glucose transport

    DEFF Research Database (Denmark)

    Cartee, Gregory D; Wojtaszewski, Jørgen F P

    2007-01-01

    160 phosphorylation in skeletal muscle. Available data from skeletal muscle support the concepts developed in adipocytes with regard to the role AS160 plays in the regulation of insulin-stimulated glucose transport. In vivo exercise, in vitro contractions, or in situ contractions can also stimulate AS......Insulin and exercise, the most important physiological stimuli to increase glucose transport in skeletal muscle, trigger a redistribution of GLUT4 glucose transporter proteins from the cell interior to the cell surface, thereby increasing glucose transport capacity. The most distal insulin...... signaling protein that has been linked to GLUT4 translocation, Akt substrate of 160 kDa (AS160), becomes phosphorylated in insulin-stimulated 3T3-L1 adipocytes; this is important for insulin-stimulated GLUT4 translocation and glucose transport. Insulin also induces a rapid and dose-dependent increase in AS...

  6. Assessing the test–retest repeatability of insulin resistance measures: Homeostasis model assessment 2 and oral glucose insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Catherine A.P. Crofts

    2017-10-01

    Full Text Available Background: Insulin resistance is commonly assessed using the homeostasis model assessment (HOMA variants. HOMA is potentially insensitive to change because of its high coefficient of variation. The repeatability coefficient is an alternative means of assessing test repeatability. To be confident of clinical change, rather than biological variation, a subsequent test needs to differ from the former by more than the repeatability coefficient using the equation. Test 1 = Test 2 ± repeatability coefficient. The repeatability coefficients for measures of insulin resistance are unknown. Aim: To compare the repeatability coefficient of HOMA2 variants (Beta-cell function [%B], insulin sensitivity [%S], insulin resistance [IR] to a dynamic measure of insulin resistance, and the oral glucose insulin sensitivity (OGIS test. Setting: The raw data from a previously used data set were reanalysed. Methods: Glycaemic and insulinaemic tests were performed on 32 men and women both with (n = 10 and without type 2 diabetes (n = 22. From these data, eight fasting tests and three 50-g oral glucose tolerance tests were used to calculate HOMA2 and OGIS. The methods of Bland and Altman assessed repeatability. Results: Repeatability coefficients for all participants for the HOMA2 %B, %S and IR variants were 72.91, 189.75 and 0.9, which equates to 89%, 135% and 89% of their respective grand means. By contrast, OGIS had a repeatability coefficient of 87.13, which equates to 21% of the grand mean. Conclusion: Because of the high repeatability coefficient relative to the grand mean, use of HOMA2 measures for assessing insulin resistance in small population studies should be reconsidered.

  7. GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism.

    Directory of Open Access Journals (Sweden)

    Hua V Lin

    Full Text Available GPR142, a putative amino acid receptor, is expressed in pancreatic islets and the gastrointestinal tract, but the ligand affinity and physiological role of this receptor remain obscure. In this study, we show that in addition to L-Tryptophan, GPR142 signaling is also activated by L-Phenylalanine but not by other naturally occurring amino acids. Furthermore, we show that Tryptophan and a synthetic GPR142 agonist increase insulin and incretin hormones and improve glucose disposal in mice in a GPR142-dependent manner. In contrast, Phenylalanine improves in vivo glucose disposal independently of GPR142. Noteworthy, refeeding-induced elevations in insulin and glucose-dependent insulinotropic polypeptide are blunted in Gpr142 null mice. In conclusion, these findings demonstrate GPR142 is a Tryptophan receptor critically required for insulin and incretin hormone regulation and suggest GPR142 agonists may be effective therapies that leverage amino acid sensing pathways for the treatment of type 2 diabetes.

  8. Does high blood glucose mean more insulin? Type 1 diabetes management in children and adolescents.

    Science.gov (United States)

    Yee, Kwang C; Edwards, Keith N

    2003-09-01

    The growth and development occurring in children and adolescents with type 1 diabetes contributes to many medical and nonmedical factors that may affect diabetic control. This article discusses the assessment of high blood sugar levels in children and adolescents with type 1 diabetes. Traditionally, diet, exercise and insulin dose are seen as the determinants of blood glucose levels in type 1 diabetic patients. While these factors are important, other practical, medical and psychosocial factors need to be considered. Appropriate management requires more than just alteration of insulin dose. Insulin injection technique, adherence to insulin and management regimens in general, psychosocial issues, the role of intercurrent infections and the development of other medical problems need to be considered. Children and adolescents may only be seen by specialist physicians at three monthly intervals. Exploring these issues with patients during routine general practitioner consultations is likely to allow early identification of treatable problems and improve long term glucose control.

  9. Glucose Induces Mouse β-Cell Proliferation via IRS2, MTOR, and Cyclin D2 but Not the Insulin Receptor

    Science.gov (United States)

    Stamateris, Rachel E.; Sharma, Rohit B.; Kong, Yahui; Ebrahimpour, Pantea; Panday, Deepika; Ranganath, Pavana; Zou, Baobo; Levitt, Helena; Parambil, Nisha Abraham; O’Donnell, Christopher P.; García-Ocaña, Adolfo

    2016-01-01

    An important goal in diabetes research is to understand the processes that trigger endogenous β-cell proliferation. Hyperglycemia induces β-cell replication, but the mechanism remains debated. A prime candidate is insulin, which acts locally through the insulin receptor. Having previously developed an in vivo mouse hyperglycemia model, we tested whether glucose induces β-cell proliferation through insulin signaling. By using mice lacking insulin signaling intermediate insulin receptor substrate 2 (IRS2), we confirmed that hyperglycemia-induced β-cell proliferation requires IRS2 both in vivo and ex vivo. Of note, insulin receptor activation was not required for glucose-induced proliferation, and insulin itself was not sufficient to drive replication. Glucose and insulin caused similar acute signaling in mouse islets, but chronic signaling differed markedly, with mammalian target of rapamycin (MTOR) and extracellular signal–related kinase (ERK) activation by glucose and AKT activation by insulin. MTOR but not ERK activation was required for glucose-induced proliferation. Cyclin D2 was necessary for glucose-induced β-cell proliferation. Cyclin D2 expression was reduced when either IRS2 or MTOR signaling was lost, and restoring cyclin D2 expression rescued the proliferation defect. Human islets shared many of these regulatory pathways. Taken together, these results support a model in which IRS2, MTOR, and cyclin D2, but not the insulin receptor, mediate glucose-induced proliferation. PMID:26740601

  10. The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity

    DEFF Research Database (Denmark)

    Kelly, Karen R; Brooks, Latina M; Solomon, Thomas

    2009-01-01

    the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% Vo(2 max)) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 +/- 190, post: 1,269 +/- 70, kcal/day; n = 9) diet on the GIP response...... to glucose in older (66.8 +/- 1.5 yr), obese (34.4 +/- 1.7 kg/m(2)) adults with impaired glucose tolerance. In addition to GIP, plasma PYY(3-36), insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in Vo(2 max) (P

  11. Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune Children's Study.

    Science.gov (United States)

    Yajnik, Chittaranjan S; Katre, Prachi A; Joshi, Suyog M; Kumaran, Kalyanaraman; Bhat, Dattatray S; Lubree, Himangi G; Memane, Nilam; Kinare, Arun S; Pandit, Anand N; Bhave, Sheila A; Bavdekar, Ashish; Fall, Caroline H D

    2015-07-01

    The Pune Children's Study aimed to test whether glucose and insulin measurements in childhood predict cardiovascular risk factors in young adulthood. We followed up 357 participants (75% follow-up) at 21 years of age who had undergone detailed measurements at 8 years of age (glucose, insulin, HOMA-IR and other indices). Oral glucose tolerance, anthropometry, plasma lipids, BP, carotid intima-media thickness (IMT) and arterial pulse wave velocity (PWV) were measured at 21 years. Higher fasting glucose, insulin and HOMA-IR at 8 years predicted higher glucose, insulin, HOMA-IR, BP, lipids and IMT at 21 years. A 1 SD change in 8 year variables was associated with a 0.10-0.27 SD change at 21 years independently of obesity/adiposity at 8 years of age. A greater rise in glucose-insulin variables between 8 and 21 years was associated with higher cardiovascular risk factors, including PWV. Participants whose HOMA-IR measurement remained in the highest quartile (n = 31) had a more adverse cardiovascular risk profile compared with those whose HOMA-IR measurement remained in the lowest quartile (n = 28). Prepubertal glucose-insulin metabolism is associated with adult cardiovascular risk and markers of atherosclerosis. Our results support interventions to improve glucose-insulin metabolism in childhood to reduce cardiovascular risk in later life.

  12. Effect of glimepiride and nateglinide on serum insulin and glucose concentration in healthy cats.

    Science.gov (United States)

    Mori, A; Lee, P; Yamashita, T; Nishimaki, Y; Oda, H; Saeki, K; Miki, Y; Mizutani, H; Ishioka, K; Honjo, T; Arai, T; Sako, T

    2009-12-01

    Glimepiride and nateglinide are two common oral hypoglycemic agents currently being used with humans suffering from Type 2 diabetes mellitus. Neither drug has been tested with cats thus far and it is currently unknown whether either of these drugs exert any effect in cats or not. The objective of this study was to determine the effect of glimepiride and nateglinide on glucose and insulin responses in healthy control cats, in order to determine their potential use in diabetic cats. The intravenous glucose tolerance tests was carried out since it is an excellent test for evaluating pancreatic beta-cell function for insulin secretion. Alterations in the insulin secretion pattern can be perceived as the earliest sign of beta-cell dysfunction in many species, including cats. Nateglinide demonstrated a quick action/short duration type effect with serum glucose nadiring and insulin response peaking at 60 and 20 minutes, respectively. Alternatively, glimepiride is medium-to-long acting with serum glucose nadiring and insulin response peaking at 180 minutes and 60 minutes, respectively. Nateglinide's potency was evident allowing it to induce a 1.5-2 higher preliminary insulin peak (3.7 +/- 1.1 pg/ml) than glimepiride's (2.5 +/- 0.1 pg/ml), albeit only for a short period of time. Because glimepiride and nateglinide have a shared mode of action, no significant differences in overall glucose AUC(0-360 min) (24,435 +/- 2,940 versus 24,782 +/- 2,354 mg min/dl) and insulin AUC(0-360 min) (410 +/- 192 versus 460 +/- 159) in healthy control cats were observed. These findings may provide useful information when choosing a hypoglycemic drug suited for the treatment of diabetic cats depending on the degree of diabetes mellitus the cat is suffering from.

  13. Changes in blood glucose and insulin responses to intravenous glucose tolerance tests and blood biochemical values in adult female Japanese black bears (Ursus thibetanus japonicus).

    Science.gov (United States)

    Kamine, Akari; Shimozuru, Michito; Shibata, Haruki; Tsubota, Toshio

    2012-02-01

    The metabolic mechanisms to circannual changes in body mass of bears have yet to be elucidated. We hypothesized that the Japanese black bear (Ursus thibetanus japonicus) has a metabolic mechanism that efficiently converts carbohydrates into body fat by altering insulin sensitivity during the hyperphagic stage before hibernation. To test this hypothesis, we investigated the changes in blood biochemical values and glucose and insulin responses to intravenous glucose tolerance tests (IVGTT) during the active season (August, early and late November). Four, adult, female bears (5-17 years old) were anesthetized with 6 mg/kg TZ (tiletamine HCl and zolazepam HCl) in combination with 0.1 mg/kg acepromazine maleate. The bears were injected intravenously with glucose (0.5 g/kg of body mass), and blood samples were obtained before, at, and intermittently after glucose injection. The basal triglycerides concentration decreased significantly with increase in body mass from August to November. Basal levels of plasma glucose and serum insulin concentrations were not significantly different among groups. The results of IVGTT demonstrated the increased peripheral insulin sensitivity and glucose tolerance in early November. In contrast, peripheral insulin resistance was indicated by the exaggerated insulin response in late November. Our findings suggest that bears shift their glucose and lipid metabolism from the stage of normal activity to the hyperphagic stage in which they show lipogenic-predominant metabolism and accelerate glucose uptake by increasing the peripheral insulin sensitivity.

  14. Insulin Pump and Continuous Glucose Monitor Initiation in Hospitalized Patients with Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Levitt, David L; Spanakis, Elias K; Ryan, Kathleen A; Silver, Kristi D

    2018-01-01

    Insulin pumps and continuous glucose monitoring (CGM) are commonly used by patients with diabetes mellitus in the outpatient setting. The efficacy and safety of initiating inpatient insulin pumps and CGM in the nonintensive care unit setting is unknown. In a prospective pilot study, inpatients with type 2 diabetes were randomized to receive standard subcutaneous basal-bolus insulin and blinded CGM (group 1, n = 5), insulin pump and blinded CGM (group 2, n = 6), or insulin pump and nonblinded CGM (group 3, n = 5). Feasibility, glycemic control, and patient satisfaction were evaluated among groups. Group 1 had lower mean capillary glucose levels, 144.5 ± 19.5 mg/dL, compared with groups 2 and 3, 191.5 ± 52.3 and 182.7 ± 59.9 mg/dL (P 1 vs. 2+3  = 0.05). CGM detected 19 hypoglycemic episodes (glucose insulin or percentage of time spent below target glucose range (180 mg/dL). On the Diabetes Treatment Satisfaction Questionnaire-Change, group 3 reported increased hyperglycemia and decreased hypoglycemia frequency compared with the other two groups, although the differences did not reach statistical significance. Insulin pump and CGM initiation are feasible during hospitalization, although they are labor intensive. Although insulin pump initiation may not lead to improved glycemic control, there is a trend toward CGM detecting a greater number of hypoglycemic episodes. Larger studies are needed to determine whether use of this technology can lower inpatient morbidity and mortality.

  15. Molecular Characterization of Insulin-Mediated Suppression of Hepatic Glucose Production In Vivo

    OpenAIRE

    Ramnanan, Christopher J.; Edgerton, Dale S.; Rivera, Noelia; Irimia-Dominguez, Jose; Farmer, Ben; Neal, Doss W.; Lautz, Margaret; Donahue, E. Patrick; Meyer, Catalina M.; Roach, Peter J.; Cherrington, Alan D.

    2010-01-01

    OBJECTIVE Insulin-mediated suppression of hepatic glucose production (HGP) is associated with sensitive intracellular signaling and molecular inhibition of gluconeogenic (GNG) enzyme mRNA expression. We determined, for the first time, the time course and relevance (to metabolic flux) of these molecular events during physiological hyperinsulinemia in vivo in a large animal model. RESEARCH DESIGN AND METHODS 24 h fasted dogs were infused with somatostatin, while insulin (basal or 8× basal) and ...

  16. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.

    Science.gov (United States)

    Kang, Changkeun; Lee, Hyunkyoung; Jung, Eun-Sun; Seyedian, Ramin; Jo, MiNa; Kim, Jehein; Kim, Jong-Shu; Kim, Euikyung

    2012-12-15

    Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Mechanism for leptin’s acute insulin-independent effect to reverse diabetic ketoacidosis

    Science.gov (United States)

    Perry, Rachel J.; Peng, Liang; Abulizi, Abudukadier; Kennedy, Lynn; Cline, Gary W.

    2017-01-01

    The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown. We examined the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced rat model of DKA. Leptin infusion reduced rates of lipolysis, hepatic glucose production (HGP), and hepatic ketogenesis by 50% within 6 hours and were independent of any changes in plasma glucagon concentrations; these effects were abrogated by coinfusion of corticosterone. Treating leptin- and corticosterone-infused rats with an adipose triglyceride lipase inhibitor blocked corticosterone-induced increases in plasma glucose concentrations and rates of HGP and ketogenesis. Similarly, adrenalectomized type 1 diabetic (T1D) rats exhibited decreased rates of lipolysis, HGP, and ketogenesis; these effects were reversed by corticosterone infusion. Leptin-induced decreases in lipolysis, HGP, and ketogenesis in DKA were also nullified by relatively small increases (15 to 70 pM) in plasma insulin concentrations. In contrast, the chronic glucose-lowering effect of leptin in a STZ-induced mouse model of poorly controlled T1D was associated with decreased food intake, reduced plasma glucagon and corticosterone concentrations, and decreased ectopic lipid (triacylglycerol/diacylglycerol) content in liver and muscle. Collectively, these studies demonstrate marked differences in the acute insulin-independent effects by which leptin reverses fasting hyperglycemia and ketoacidosis in a rodent model of DKA versus the chronic pleotropic effects by which leptin reverses hyperglycemia in a non-DKA rodent model of T1D. PMID:28112679

  18. Insulin downregulates the expression of the Ca2+-activated nonselective cation channel TRPM5 in pancreatic islets from leptin-deficient mouse models

    OpenAIRE

    Colsoul, Barbara; Jacobs, Griet; Philippaert, Koenraad; Owsianik, Grzegorz; Segal, Andrei; Nilius, Bernd; Voets, Thomas; Schuit, Frans; Vennekens, Rudi

    2013-01-01

    We recently proposed that the transient receptor potential melastatin 5 (TRPM5) cation channel contributes to glucose-induced electrical activity of the β cell and positively influences glucose-induced insulin release and glucose homeostasis. In this study, we investigated Trpm5 expression and function in pancreatic islets from mouse models of type II diabetes. Gene expression analysis revealed a strong reduction of Trpm5 mRNA levels in pancreatic islets of db/db and ob/ob mice. The glucose-i...

  19. Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians

    Science.gov (United States)

    Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. We investigated the associations of meat intake and the intera...

  20. Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: A meta-analysis of 50,345 Caucasians

    NARCIS (Netherlands)

    A.M. Fretts (Amanda M.); J.L. Follis (Jack ); J.A. Nettleton (Jennifer ); R.N. Lemaitre (Rozenn ); J.S. Ngwa; M.K. Wojczynski (Mary ); I.-P. Kalafati (Ioanna-Panagiota); T.V. Varga (Tibor V.); A.C. Frazier-Wood (Alexis C.); D.K. Houston (Denise); J. Lahti (Jari); U. Ericson (Ulrika); E.H. van den Hooven (Edith); V. Mikkilä (Vera); J.C. Kiefte-de Jong (Jessica); D. Mozaffarian (Dariush); K.M. Rice (Kenneth); F. Renström (Frida); K.E. North (Kari); N.M. McKeown (Nicola ); M.F. Feitosa (Mary Furlan); S. Kanoni (Stavroula); C.E. Smith (Caren); M. Garcia (Melissa); A.-M. Tiainen (Anna-Maija); E. Sonestedt (Emily); A. Manichaikul (Ani); F.J.A. van Rooij (Frank); M. Dimitriou (Maria); O. Raitakari (Olli); J.S. Pankow (James); L. Djoussé (Luc); M.A. Province (Mike); F.B. Hu (Frank); C.-Q. Lai (Chao-Qiang); M.F. Keller (Margaux); M.-M. Perälä (Mia-Maria); J.I. Rotter (Jerome I.); A. Hofman (Albert); M.J. Graff (Maud J.L.); M. Kähönen (Mika); K. Mukamal (Kenneth); I. Johansson (Ingegerd); J.M. Ordovas (Jose); Y. Liu (YongMei); S. Männistö (Satu); A.G. Uitterlinden (André); P. Deloukas (Panagiotis); I. Seppälä (Ilkka); B.M. Psaty (Bruce); L.A. Cupples (Adrienne); I.B. Borecki (Ingrid); P.W. Franks (Paul W.); D.K. Arnett (Donna); M.A. Nalls (Michael); K. Hagen (Knut); M. Orho-Melander (Marju); O.H. Franco (Oscar); T. Lehtimäki (Terho); G.V. Dedoussis (George); J.B. Meigs (James); D.S. Siscovick (David)

    2015-01-01

    textabstractBackground: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the

  1. Effects of different levels of coconut fiber on blood glucose, serum insulin and minerals in rats.

    Science.gov (United States)

    Sindurani, J A; Rajamohan, T

    2000-01-01

    The effect of neutral detergent fiber (NDF) from coconut kernel (Cocos nucifera L) in rats fed 5%, 15% and 30% level on the concentration of blood glucose, serum insulin and excretion of minerals was studied. Increase in the intake of fiber resulted in significant decrease in the level of blood glucose and serum insulin. Faecal excretion of Cu, Cr, Mn, Mg, Zn and Ca was found to increase in rats fed different levels of coconut fiber when compared to fiber free group. The result of the present investigation suggest that inclusion of coconut fiber in the diet results in significant hypoglycemic action.

  2. Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents

    OpenAIRE

    Perry, Rachel J.; Cardone, Rebecca L.; Petersen, Max C.; Zhang, Dongyan; Fouqueray, Pascale; Hallakou-Bozec, Sophie; Bolze, Sébastien; Shulman, Gerald I.; Petersen, Kitt Falk; Kibbey, Richard G.

    2016-01-01

    Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1–3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the β-cell stimulatory effect of imeglimin is solely or par...

  3. Fat intake leads to differential response of rat adipocytes to glucose, insulin and ascorbic acid.

    Science.gov (United States)

    Garcia-Diaz, Diego F; Campion, Javier; Arellano, Arianna V; Milagro, Fermin I; Moreno-Aliaga, Maria J; Martinez, J Alfredo

    2012-04-01

    Antioxidant-based treatments have emerged as novel and interesting approaches to counteract fat accumulation in obesity and associated metabolic disturbances. Adipocytes from rats that were fed on chow or high-fat diet (HFD) for 50 d were isolated (primary adipocytes) and incubated (72 h) on low (LG; 5.6 mmol/L) or high (HG; 25 mmol/L) glucose levels, in the presence or absence of 1.6 nmol/L insulin and 200 μmol/L vitamin C (VC). Adipocytes from HFD-fed animals presented lower insulin-induced glucose uptake, lower lactate and glycerol release, and lower insulin-induced secretion of some adipokines as compared with controls. HG treatment restored the blunted response to insulin regarding apelin secretion in adipocytes from HFD-fed rats. VC treatment inhibited the levels of nearly all variables, irrespective of the adipocytes' dietary origin. The HG treatment reduced adipocyte viability, and VC protected from this toxic effect, although more drastically in control adipocytes. Summing up, in vivo chow or HFD intake determines a differential response to insulin and glucose treatments that appears to be dependent on the insulin-resistance status of the adipocytes, while VC modifies some responses from adipocytes independently of the previous dietary intake of the animals.

  4. Gestational Protein Restriction Impairs Insulin-Regulated Glucose Transport Mechanisms in Gastrocnemius Muscles of Adult Male Offspring

    Science.gov (United States)

    Blesson, Chellakkan S.; Sathishkumar, Kunju; Chinnathambi, Vijayakumar

    2014-01-01

    Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet–exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet–fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor

  5. Gestational protein restriction impairs insulin-regulated glucose transport mechanisms in gastrocnemius muscles of adult male offspring.

    Science.gov (United States)

    Blesson, Chellakkan S; Sathishkumar, Kunju; Chinnathambi, Vijayakumar; Yallampalli, Chandrasekhar

    2014-08-01

    Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet-exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet-fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor

  6. An injectable particle-hydrogel hybrid system for glucose-regulatory insulin delivery.

    Science.gov (United States)

    Zhao, Fuli; Wu, Di; Yao, Dan; Guo, Ruiwei; Wang, Weiwei; Dong, Anjie; Kong, Deling; Zhang, Jianhua

    2017-12-01

    Long-term and daily subcutaneous injections of insulin for the treatment of insulin-dependent diabetic patients often lead to poor patient compliance and undesired complications. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, their applications are limited by clinically irrelevant glucose-responsive range, slow response rate, low tissue-adhesiveness and poor biodegradability, undesirable leakage at normoglycemic state. Herein, we report a novel implantable insulin hydrogel for glucose-regulated delivery of insulin based on a unique particle-hydrogel hybrid platform featuring fast glucose responsiveness at physiological pH, shear-thinning behavior for injection, tissue-adhesive function for long-lasting adherence, and full biodegradability for safe use. The system was thoroughly characterized both in vitro and in vivo and was demonstrated to hold these unique functions. Using streptozotocin-induced diabetic mice as a model, it was shown that a single subcutaneous injection of the insulin-loaded particle-hydrogel formulation led to quasi-steady-state blood glucose levels within the normal range for about two weeks. In addition, the preparation of the formulation only involved simple mixing and self-assembling processes, and thus it had great scalability and reproducibility for practical use. The highly feasible preparation, excellent performance, inherent biocompatibility and biodegradability make this novel composite hydrogel promising platform for diabetes therapy. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, these hydrogels, mostly based on a variety of PBA-containing acrylamide monomers, are still far from clinical reality. Building upon a unique particle-hydrogel hybrid platform, herein we

  7. A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

    International Nuclear Information System (INIS)

    Namba, Hiroki; Nakagawa, Keiichi; Iyo, Masaomi; Fukushi, Kiyoshi; Irie, Toshiaki

    1994-01-01

    A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. (orig.)

  8. Does green tea affect postprandial glucose, insulin and satiety in healthy subjects: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lindstedt Sandra

    2010-11-01

    Full Text Available Abstract Background Results of epidemiological studies have suggested that consumption of green tea could lower the risk of type 2 diabetes. Intervention studies show that green tea may decrease blood glucose levels, and also increase satiety. This study was conducted to examine the postprandial effects of green tea on glucose levels, glycemic index, insulin levels and satiety in healthy individuals after the consumption of a meal including green tea. Methods The study was conducted on 14 healthy volunteers, with a crossover design. Participants were randomized to either 300 ml of green tea or water. This was consumed together with a breakfast consisting of white bread and sliced turkey. Blood samples were drawn at 0, 15, 30, 45, 60, 90, and 120 minutes. Participants completed several different satiety score scales at the same times. Results Plasma glucose levels were higher 120 min after ingestion of the meal with green tea than after the ingestion of the meal with water. No significant differences were found in serum insulin levels, or the area under the curve for glucose or insulin. Subjects reported significantly higher satiety, having a less strong desire to eat their favorite food and finding it less pleasant to eat another mouthful of the same food after drinking green tea compared to water. Conclusions Green tea showed no glucose or insulin-lowering effect. However, increased satiety and fullness were reported by the participants after the consumption of green tea. Trial registration number NCT01086189

  9. Does green tea affect postprandial glucose, insulin and satiety in healthy subjects: a randomized controlled trial.

    Science.gov (United States)

    Josic, Julija; Olsson, Anna Tholén; Wickeberg, Jennie; Lindstedt, Sandra; Hlebowicz, Joanna

    2010-11-30

    Results of epidemiological studies have suggested that consumption of green tea could lower the risk of type 2 diabetes. Intervention studies show that green tea may decrease blood glucose levels, and also increase satiety. This study was conducted to examine the postprandial effects of green tea on glucose levels, glycemic index, insulin levels and satiety in healthy individuals after the consumption of a meal including green tea. The study was conducted on 14 healthy volunteers, with a crossover design. Participants were randomized to either 300 ml of green tea or water. This was consumed together with a breakfast consisting of white bread and sliced turkey. Blood samples were drawn at 0, 15, 30, 45, 60, 90, and 120 minutes. Participants completed several different satiety score scales at the same times. Plasma glucose levels were higher 120 min after ingestion of the meal with green tea than after the ingestion of the meal with water. No significant differences were found in serum insulin levels, or the area under the curve for glucose or insulin. Subjects reported significantly higher satiety, having a less strong desire to eat their favorite food and finding it less pleasant to eat another mouthful of the same food after drinking green tea compared to water. Green tea showed no glucose or insulin-lowering effect. However, increased satiety and fullness were reported by the participants after the consumption of green tea. NCT01086189.

  10. Growth factors, glucose and insulin kinetics after low dose growth hormone in HIV - lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Flyvbjerg, Allan

    2006-01-01

    OBJECTIVES: Low-dose growth hormone (GH) administration has been suggested as a treatment for HIV-lipodystrophy. METHODS: Postglucose GH-secretion, kinetics of insulin-like growth factors (IGFs), insulin, and glucose metabolism were examined in six male HIV-infected lipodystrophic patients (two...... normal-weight patients with normal glucose-tolerance (NGT), two normal-weight with impaired glucose-tolerance (IGT), and two obese patients with diabetes (DM)) during a 16 weeks open-labelled pilot-study of low-dose GH, 0.7 mg/day. RESULTS: DM, compared to NGT and IGT, displayed an impaired rebound of GH...... during a 5h oral glucose-tolerance test. Near lower normal limits in all patients before GH-therapy, total and free IGF-I increased between 87 and 152% during the GH-therapy (Pupper normal limits in all patients with the highest incremental percentages shown in DM. A slight...

  11. High Glucose Predisposes Gene Expression and ERK Phosphorylation to Apoptosis and Impaired Glucose-Stimulated Insulin Secretion via the Cytoskeleton

    Science.gov (United States)

    Yeo, Ronne Wee Yeh; Yang, Kaiyuan; Li, GuoDong; Lim, Sai Kiang

    2012-01-01

    Chronic high glucose (HG) inflicts glucotoxicity on vulnerable cell types such as pancreatic β cells and contributes to insulin resistance and impaired insulin secretion in diabetic patients. To identify HG-induced cellular aberrations that are candidate mediators of glucotoxicity in pancreatic β cells, we analyzed gene expression in ERoSHK6, a mouse insulin-secreting cell line after chronic HG exposure (six-day exposure to 33.3 mM glucose). Chronic HG exposure which reduced glucose-stimulated insulin secretion (GSIS) increased transcript levels of 185 genes that clustered primarily in 5 processes namely cellular growth and proliferation; cell death; cellular assembly and organization; cell morphology; and cell-to-cell signaling and interaction. The former two were validated by increased apoptosis of ERoSHK6 cells after chronic HG exposure and reaffirmed the vulnerability of β cells to glucotoxicity. The three remaining processes were partially substantiated by changes in cellular morphology and structure, and instigated an investigation of the cytoskeleton and cell-cell adhesion. These studies revealed a depolymerized actin cytoskeleton that lacked actin stress fibers anchored at vinculin-containing focal adhesion sites as well as loss of E-cadherin-mediated cell-cell adherence after exposure to chronic HG, and were concomitant with constitutive ERK1/2 phosphorylation that was refractory to serum and glucose deprivation. Although inhibition of ERK phosphorylation by PD98059 promoted actin polymerization, it increased apoptosis and GSIS impairment. These findings suggest that ERK phosphorylation is a proximate regulator of cellular processes targeted by chronic HG-induced gene expression and that dynamic actin polymerization and depolymerization is important in β cell survival and function. Therefore, chronic HG alters gene expression and signal transduction to predispose the cytoskeleton towards apoptosis and GSIS impairment. PMID:23024780

  12. Does green tea affect postprandial glucose, insulin and satiety in healthy subjects: a randomized controlled trial

    OpenAIRE

    Josic, Julija; Olsson, Anna Thol?n; Wickeberg, Jennie; Lindstedt, Sandra; Hlebowicz, Joanna

    2010-01-01

    Abstract Background Results of epidemiological studies have suggested that consumption of green tea could lower the risk of type 2 diabetes. Intervention studies show that green tea may decrease blood glucose levels, and also increase satiety. This study was conducted to examine the postprandial effects of green tea on glucose levels, glycemic index, insulin levels and satiety in healthy individuals after the consumption of a meal including green tea. Methods The study was conducted on 14 hea...

  13. Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

    DEFF Research Database (Denmark)

    Hansen, Tue Haldor; Vestergaard, Henrik; Jørgensen, Torben

    2015-01-01

    ,641 glucose tolerant controls, respectively. Quantitative trait analyses were performed in up to 13,605 individuals subjected to an OGTT or blood samples obtained after an overnight fast, as well as in 596 individuals subjected to an IVGTT. Results: Analyses of fasting and OGTT-derived quantitative traits did...... of this variant in PTBP1 on glucose stimulated insulin release open for further investigation. However, the present study does not support the hypothesis that the variant confers risk of type 2 diabetes....

  14. Insulin and glucose play a role in foam cell formation and function

    Directory of Open Access Journals (Sweden)

    Keller Susanna R

    2006-06-01

    Full Text Available Abstract Background Foam cell formation in diabetic patients often occurs in the presence of high insulin and glucose levels. To test whether hyperinsulinemic hyperglycemic conditions affect foam cell differentiation, we examined gene expression, cytokine production, and Akt phosphorylation in human monocyte-derived macrophages incubated with two types of oxidized low density lipoprotein (LDL, minimally modified LDL (mmLDL and extensively oxidized LDL (OxLDL. Methods and results Using Affymetrix GeneChip® arrays, we found that several genes directly related to insulin signaling were changed. The insulin receptor and glucose-6-phosphate dehydrogenase were upregulated by mmLDL and OxLDL, whereas insulin-induced gene 1 was significantly down-regulated. In hyperinsulinemic hyperglycemic conditions, modified LDL upregulated Akt phosphorylation and expression of the insulin-regulated aminopeptidase. The level of proinflammatory cytokines, IL-lβ, IL-12, and IL-6, and of a 5-lipoxygenase eicosanoid, 5-hydroxyeicosatetraenoic acid (5-HETE, was also increased. Conclusion These results suggest that the exposure of macrophages to modified low density lipoproteins in hyperglycemic hyperinsulinemic conditions affects insulin signaling and promotes the release of proinflammatory stimuli, such as cytokines and eicosanoids. These in turn may contribute to the development of insulin resistance.

  15. An Amperometric Glucose Sensor Integrated into an Insulin Delivery Cannula: In Vitro and In Vivo Evaluation.

    Science.gov (United States)

    Ward, W Kenneth; Heinrich, Gabriel; Breen, Matthew; Benware, Sheila; Vollum, Nicole; Morris, Kristin; Knutsen, Chad; Kowalski, Joseph D; Campbell, Scott; Biehler, Jerry; Vreeke, Mark S; Vanderwerf, Scott M; Castle, Jessica R; Cargill, Robert S

    2017-04-01

    Labeling prohibits delivery of insulin at the site of subcutaneous continuous glucose monitoring (CGM). Integration of the sensing and insulin delivery functions into a single device would likely increase the usage of CGM in persons with type 1 diabetes. To understand the nature of such interference, we measured glucose at the site of bolus insulin delivery in swine using a flexible electrode strip that was laminated to the outer wall of an insulin delivery cannula. In terms of sensing design, we compared H 2 O 2 -measuring sensors biased at 600 mV with redox mediator-type sensors biased at 175 mV. In H 2 O 2 -measuring sensors, but not in sensors with redox-mediated chemistry, a spurious rise in current was seen after insulin lis-pro boluses. This prolonged artifact was accompanied by electrode poisoning. In redox-mediated sensors, the patterns of sensor signals acquired during delivery of saline and without any liquid delivery were similar to those acquired during insulin delivery. Considering in vitro and in vivo findings together, it became clear that the mechanism of interference is the oxidation, at high bias potentials, of phenolic preservatives present in insulin formulations. This effect can be avoided by the use of redox mediator chemistry using a low bias potential.

  16. Sexual dimorphism in the lasting effects of moderate caloric restriction during gestation on energy homeostasis in rats is related with fetal programming of insulin and leptin resistance

    Directory of Open Access Journals (Sweden)

    Palou Mariona

    2010-08-01

    Full Text Available Abstract Aim We aimed to characterize the lasting effect of moderate caloric restriction during early pregnancy on offspring energy homeostasis, by focusing on the effects on food intake and body weight as well as on the insulin and leptin systems. Methods Male and female offspring of 20% caloric restricted dams (from 1 to 12 days of pregnancy (CR and from control dams were studied. These animals were fed after weaning with a normal-fat (NF diet until the age of 4 months, and then moved to a high-fat (HF diet. Blood parameters were measured under fed and 14-h fasting conditions at different ages (2, 4 and 5 months. Food preferences were also assessed in adult animals. Results Accumulated caloric intake from weaning to the age of 5 months was higher in CR animals compared with their controls, and this resulted in higher body weight in adulthood in males, but not in females. Both male and female CR animals already showed higher insulin levels at the age of 2 months, under fed conditions, and higher HOMA-IR from the age of 4 months, compared with their controls. CR male animals, but not females, displayed higher preference for fat-rich food than their controls in adulthood and higher circulating leptin levels when they were under HF diet. Conclusion It is suggested that hyperinsulinemia may play a role in the etiology of hyperphagia in the offspring of caloric restricted animals during gestation, with different outcomes on body weight depending on the gender, which could be associated with different programming effects on later leptin resistance.

  17. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy

    DEFF Research Database (Denmark)

    Battelino, T; Conget, I; Olsen, B

    2012-01-01

    The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes.......The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes....

  18. Effects of high glucose on caveolin-1 and insulin signaling in 3T3-L1 adipocytes.

    Science.gov (United States)

    Palacios-Ortega, Sara; Varela-Guruceaga, Maider; Martínez, J Alfredo; de Miguel, Carlos; Milagro, Fermín I

    2016-01-01

    Adipocytes exposed to high glucose concentrations exhibit impaired metabolic function, including an increase of oxidative and proinflammatory factors that might favor the development of insulin resistance. Caveolin-1 (Cav-1) is a key mediator of the insulin transduction pathway whose expression is significantly enhanced during adipocyte differentiation. In this work, we studied the effects of high glucose concentration on the regulation of Cav-1 expression and activation and its relation to the insulin signaling pathway during the adipogenic process and in long-term differentiated adipocytes. Both, long-term high glucose exposure during adipogenesis and short-term glucose incubation of mature adipocytes, promoted triglyceride accumulation in 3T3-L1 cells. The short-term exposure of mature adipocytes to high glucose significantly reduced the sensitivity to insulin of Cav-1, insulin receptor (IR) and potein kinase B (AKT-2) phosphorylation, as well as insulin-induced deoxyglucose uptake. Adipocytes differentiated in the presence of high glucose lost Cav-1 and IR response to insulin-stimulated phosphorylation, but maintained the insulin sensitivity of AKT-2 phosphorylation and deoxyglucose uptake. Although long-term high glucose exposure increased DNA methylation in Cav-1 promoter, Cav-1 expression was not affected. Moreover, these cells showed an increase of Cav-1, IR and AKT-2 protein content, pointing to an adaptive response induced by the long-term high glucose exposure.

  19. Mathematical modeling of the glucose-insulin system

    DEFF Research Database (Denmark)

    Palumbo, Pasquale; Ditlevsen, Susanne; Bertuzzi, Alessandro

    2013-01-01

    Mathematical modeling of the glucose–insulin feedback system is necessary to the understanding of the homeostatic control, to analyze experimental data, to identify and quantify relevant biophysical parameters, to design clinical trials and to evaluate diabetes prevention or disease modification...

  20. Postprandial Glucose and Insulin Responses to Grain Products in ...

    African Journals Online (AJOL)

    Prof. Ogunji

    disrupt the food structure increase the glycaemic and insulinemic responses as seen in maize and bread in this study. Whole grain cereal products with low-GI characteristics might thus be particularly advantageous with respect to the insulin resistance syndrome since from this study the low glycaemic index meals (acha ...

  1. Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

    DEFF Research Database (Denmark)

    van Opstal, Anna M.; Akintola, Abimbola A.; Elst, Marjan van der

    2017-01-01

    The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this s......The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease....... In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood......-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose...

  2. Postprandial glucose and insulin responses to various snacks of equivalent carbohydrate content in normal subjects.

    Science.gov (United States)

    Shively, C A; Apgar, J L; Tarka, S M

    1986-03-01

    To evaluate glucose and insulin responses after ingestion of snacks, we gave healthy, nondiabetic male subjects carbohydrate equivalent (25 g) snacks or isocaloric (265 kcal) snack meals in a random crossover design. Individual snacks composed of either a milk chocolate bar, granola bar, chocolate milk, peanut butter cups, yogurt, or potato chips produced similar glucose response curves. Plasma glucose concentrations were lower (p less than or equal to 0.05) at 30 and 60 min postprandially than after a corresponding oral glucose challenge. In contrast, insulin responses to the snacks exhibited a two-fold variation in peak values. Isocaloric snack meals of cereal-milk, cheese sandwich-milk, and peanut butter sandwich-chocolate milk produced glucose and insulin responses similar to individual snacks. Although glucose concentrations at 60 min fell somewhat below baseline values after each snack, clinical hypoglycemia was not evident. These data clearly indicate a similarity in glycemic response among normal individuals consuming a variety of common snacks.

  3. Trefoil factor 3 (TFF3 expression is regulated by insulin and glucose

    Directory of Open Access Journals (Sweden)

    Girolamo Jose Barrera Roa

    2013-04-01

    Full Text Available Introduction: Trefoil factors are effector molecules in gastrointestinal tract physiology. They are classified into three groups: the gastric peptides (TFF1, spasmolytic peptide (TFF2 and intestinal trefoil factor (TFF3. Previous studies have shown that trefoil factors are located and expressed in human endocrine pancreas suggesting that TFF3 play a role in: a pancreatic cells migration, b β-cell mitosis, and c pancreatic cells regeneration. We speculated that the presence of TFF3 in pancreas, could be associated to a possible regulation mechanism by insulin and glucose. To date, there are not reports whether the unbalance in carbohydrate metabolism observed in diabetes could affect the production or expression of TFF3.Methods: We determined the TFF3 levels and expression by immunoassay (ELISA and semi-quantitative RT-PCR technique respectively, of intestinal epithelial cells (HT-29 treated with glucose and insulin. Also,Real Time-PCR (RTq-PCR was done.Results: Increasing concentrations of glucose improved TFF3 expression and these levels were further elevated after insulin treatment. Insulin treatment also led to the up-regulation of human sodium/glucose transporter 1 (hSGLT1, which further increases intracellular glucose levels. Finally, we investigated theTFF3 levels in serum of diabetes mellitus type 1 (T1DM and healthy patients. Here we shown that serum TFF3 levels were down-regulated in T1DM and this levels were up-regulated after insulin treatment. Also, the TFF3 levels of healthy donors were up-regulated 2 h after breakfast.Conclusion: Our fi ndings suggest for the fi rst time that insulin signaling is important for TFF3 optimal expression in serum and intestinal epithelial cells.

  4. Effects of a fibre-enriched milk drink on insulin and glucose levels in healthy subjects

    Directory of Open Access Journals (Sweden)

    Pilvi Taru K

    2009-10-01

    Full Text Available Abstract Background The glycaemic response to foods is dependent on the quality and content of carbohydrates. Carbohydrates in the form of dietary fibre have favourable effects on insulin and glucose metabolism and may help to control energy intake. Dairy products have a relatively low carbohydrate content, and most of the carbohydrate is in the form of lactose which causes gastrointestinal symptoms in part of the population. In order to avoid these symptoms, dairy products can be replaced with lactose-free dairy products which are on the market in many parts of the world. However, the effects of lactose-free products on insulin and glucose metabolism have not been studied. Methods In the present study, we investigated the effects of 1 a lactose-free milk drink, 2 a novel fibre-enriched, fat- and lactose-free milk drink and 3 normal fat-free milk on serum glucose and insulin levels and satiety using a randomized block design. Following an overnight fast, 26 healthy volunteers ingested 200 ml of one of these drinks on three non-consecutive days. Insulin and glucose levels and subjective satiety ratings were measured before the ingestion of the milk product and 20, 40, 60, 120 and 180 minutes after ingestion. The responses were calculated as the area under the curve subtracted by the baseline value (AUC minus baseline. Results The insulin response was significantly lower for the fibre-enriched milk drink than it was for the other milk products (AUC, P = 0.007. There were no differences in the response for glucose or in the AUC for the subjective satiety ratings between the studied milk products. Conclusion The present results suggest that this novel milk drink could have positive effects on insulin response.

  5. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

    NARCIS (Netherlands)

    R. Saxena (Richa); M.-F. Hivert (Marie-France); C. Langenberg (Claudia); T. Tanaka (Toshiko); J.S. Pankow (James); P. Vollenweider (Peter); V. Lyssenko (Valeriya); N. Bouatia-Naji (Nabila); J. Dupuis (Josée); A.U. Jackson (Anne); W.H.L. Kao (Wen); M. Li (Man); N.L. Glazer (Nicole); A.K. Manning (Alisa); J. Anluan (Jian); H.M. Stringham (Heather); I. Prokopenko (Inga); T. Johnson (Toby); N. Grarup (Niels); T.W. Boesgaard (Trine); C. Lecoeur (Cécile); P. Shrader (Peter); J.R. O´Connell; E. Ingelsson (Erik); D.J. Couper (David); K. Rice (Kenneth); K. Song (Kijoung); C.H. Andreasen (Camilla); C. Dina (Christian); A. Köttgen (Anna); O.L. Bacquer (Olivier); F. Pattou (François); J. Taneera (Jalal); V. Steinthorsdottir (Valgerdur); D. Rybin (Denis); K.G. Ardlie (Kristin); M.J. Sampson (Michael); L. Qi (Lu); M.V. Hoek; M.N. Weedon (Michael); Y.S. Aulchenko (Yurii); B.F. Voight (Benjamin); H. Grallert (Harald); B. Balkau (Beverley); R.N. Bergman (Richard); S.J. Bielinski (Suzette); A. Bonnefond (Amélie); L.L. Bonnycastle (Lori); K. Borch-Johnsen; Y. Böttcher (Yvonne); E. Brunner (Eric); T.A. Buchanan (Thomas); S. Bumpstead (Suzannah); C. Cavalcanti-Proença (Christine); G. Charpentier (Guillaume); Y.D.I. Chen (Yii-Der Ida); P.S. Chines (Peter); F.S. Collins (Francis); M. Cornelis (Marilyn); G. Crawford (Gabe); J. Delplanque (Jerome); A.S.F. Doney (Alex); J.M. Egan (Josephine); M.R. Erdos (Michael); M. Firmann (Mathieu); N.G. Forouhi (Nita); C.S. Fox (Caroline); M. Goodarzi (Mark); J. Graessler (Jürgen); A. Hingorani (Aroon); B. Isomaa (Bo); T. Jørgensen (Torben); M. Kivimaki (Mika); P. Kovacs (Peter); K. Krohn (Knut); M. Kumari (Meena); T. Lauritzen (Torsten); C. Lévy-Marchal (Claire); V. Mayor (Vladimir); J.B. McAteer (Jarred); D. Meyre (David); B.D. Mitchell (Braxton); K.L. Mohlke (Karen); M.A. Morken (Mario); N. Narisu (Narisu); C.N.A. Palmer (Colin); R. Pakyz (Ruth); L. Pascoe (Laura); F. Payne (Felicity); D. Pearson (Daniel); W. Rathmann (Wolfgang); A. Sandbaek (Annelli); A.A. Sayer; L.J. Scott (Laura); S.J. Sharp (Stephen); E.J.G. Sijbrands (Eric); A. Singleton (Andrew); D.S. Siscovick (David); N.L. Smith (Nicholas); T. Sparsø (Thomas); A.J. Swift (Amy); H. Syddall (Holly); G. Thorleifsson (Gudmar); A. Tönjes (Anke); T. Tuomi (Tiinamaija); J. Tuomilehto (Jaakko); T.T. Valle (Timo); G. Waeber (Gérard); A. Walley (Andrew); D. Waterworth (Dawn); E. Zeggini (Eleftheria); J.H. Zhao (Jing Hua); G. Consortium (Giant); T. Illig (Thomas); H.E. Wichmann (Erich); J.F. Wilson (James); C.M. van Duijn (Cornelia); F.B. Hu (Frank); A.D. Morris (Andrew); T.M. Frayling (Timothy); A.T. Hattersley (Andrew); U. Thorsteinsdottir (Unnur); J-A. Zwart (John-Anker); P. Nilsson (Peter); A.C. Syvänen; A.R. Shuldiner (Alan); M. Walker (Mark); S.R. Bornstein (Stefan); P. Schwarz (Peter); G.H. Williams (Gordon); D.M. Nathan (David); J. Kuusisto (Johanna); M. Laakso (Markku); C. Cooper (Charles); M. Marmot (Michael); L. Ferrucci (Luigi); V. Mooser (Vincent); M. Stumvoll (Michael); R.J.F. Loos (Ruth); D. Altshuler (David); B.M. Psaty (Bruce); J.I. Rotter (Jerome); E.A. Boerwinkle (Eric); T. Hansen (Torben); O. Pedersen (Oluf); J.C. Florez (Jose); M.I. McCarthy (Mark); M. Boehnke (Michael); I.E. Barroso (Inês); R. Sladek (Rob); P. Froguel (Philippe); J.B. Meigs (James); L. Groop (Leif); N.J. Wareham (Nick); R.M. Watanabe (Richard)

    2010-01-01

    textabstractGlucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n =

  6. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

    DEFF Research Database (Denmark)

    Saxena, Richa; Hivert, Marie-France; Langenberg, Claudia

    2010-01-01

    Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620)...

  7. Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients

    NARCIS (Netherlands)

    Jazet, I. M.; Schaart, G.; Gastaldelli, A.; Ferrannini, E.; Hesselink, M. K.; Schrauwen, P.; Romijn, J. A.; Maassen, J. A.; Pijl, H.; Ouwens, D. M.; Meinders, A. E.

    2008-01-01

    Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with

  8. Absence of an acute insulin response predicts onset of type 2 diabetes in a Caucasian population with impaired glucose tolerance

    NARCIS (Netherlands)

    Nijpels, G.; Boorsma, W.; Dekker, J.M.; Hoeksema, F.; Kostense, P.J.; Bouter, L.M.; Heine, R.J.

    2008-01-01

    Context: In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes mellitus (T2DM). However, few studies have used criterion standard measures to asses the predictive value of impaired insulin secretion

  9. Glucose and insulin variations in patients during the time course of a FDG-PET study and implications for the 'glucose-corrected' SUV

    International Nuclear Information System (INIS)

    Hadi, Mohiuddin; Bacharach, Stephen L.; Whatley, Millie; Libutti, Steven K.; Straus, Stephen E.; Rao, V. Koneti; Wesley, Robert; Carrasquillo, Jorge A.

    2008-01-01

    Introduction: 2-Deoxy-2[ 18 F]fluoro-D-glucose (FDG) positron emission tomography (PET) has an established role in the evaluation of cancer. Generally, tumor uptake and response to treatment are evaluated using the standardized uptake value (SUV). Some authors have proposed correcting SUV for glucose levels. Insulin is also thought to influence tumor uptake by changing uptake in other tissues. However, little attention has been paid to understanding the variability of glucose or insulin during a single PET study. Method: We studied the biological and instrumental variability of glucose and insulin measurements in 71 nondiabetic patients undergoing FDG-PET studies. Multiple glucose measurements were obtained in all 71 subjects, and in 69 of these 71 subjects, multiple serum insulin measurements were made. We determined the coefficient of observed variation (CV ow ) and the coefficient of variation attributable to biological variability (CV bv ) for both glucose and insulin. Results: The mean glucose concentration was 78.9±13.5 mg/dl. The mean insulin value was 6.49±5.92 μU/ml. The weighted mean CV ow and CV bv was 5.0% and 3.6%, respectively, for glucose and 14.2% and 8.3%, respectively, for insulin. Conclusions: Variations in the range of 3.6% are observed in glucose measurements during the time course of an FDG scan even after accounting for analytical error; larger variations of 8.3% are observed in insulin levels. Therefore, corrections of SUV for blood glucose, especially if obtained from single measurements, can introduce additional errors of at least this much

  10. Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B

    DEFF Research Database (Denmark)

    Hribal, M L; Presta, I; Procopio, T

    2011-01-01

    The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry.......The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry....

  11. Expression of the major insulin regulatable glucose transporter (GLUT4) in skeletal muscle of noninsulin-dependent diabetic patients and healthy subjects before and after insulin infusion

    DEFF Research Database (Denmark)

    Andersen, P H; Lund, S; Vestergaard, H

    1993-01-01

    In a cross-sectional study we have examined the regulatory effect of insulin in vivo on the major insulin regulatable glucose transporter (GLUT4) in vastus lateralis muscle from 12 noninsulin-dependent diabetes mellitus (NIDDM) patients and 8 healthy control subjects. Insulin-stimulated glucose...... uptake rate in peripheral tissue was decreased by 41% (P 2 groups in muscle biopsies obtained...... in the basal state. In healthy subjects, 4 h of insulin infusion (2 mU/kg/min) induced a 31% reduction (P

  12. Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

    International Nuclear Information System (INIS)

    Perret, Pascale; Slimani, Lotfi; Briat, Arnaud; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine; Halimi, Serge; Demongeot, Jacques

    2007-01-01

    Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using 125 I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p < 0.05; heart, p < 0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p < 0.001; muscle, p < 0.001; heart, p < 0.01) whereas no significant changes were observed in fructose-fed rats. This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging. (orig.)

  13. Glucose-induced time-dependent potentiation of insulin release, but not islet blood perfusion, in anesthetized rats.

    Science.gov (United States)

    Jansson, Leif; Bodin, Birgitta; Källskog, Orjan

    2008-01-01

    Repeated administration of glucose in vivo leads to a time-dependent potentiation of insulin release. Glucose is also known to stimulate pancreatic islet blood flow, but whether this is associated with a time-dependent potentiation is unknown. We therefore repeatedly administered glucose to anesthetized rats and evaluated effects on insulin release and islet blood flow. Male Wistar-Furth rats, anesthetized with thiobutabarbital, were injected intravenously with 1 ml of saline or glucose at times 0, 30 and 60 min. The combinations used were saline + saline + saline (SSS), glucose + saline + saline (GSS), saline + saline + glucose (SSG) and glucose + glucose + glucose (GGG). Regional organ blood flow values were measured 3 min after the final injection with a microsphere technique, and at this time also serum insulin concentrations were determined with ELISA. Serum insulin concentrations as well as total pancreatic, pancreatic islet and duodenal blood flow were higher in SSG and GGG-treated rats when compared to those given SSS and GSS. However, only insulin concentrations, not blood flow values, were higher in GGG rats when compared to SSG animals. Glucose-induced time-dependent potentiation of insulin release occurs in vivo in thiobutabarbital-anesthetized rats, but is not associated with a further increase in islet blood flow.

  14. Mitochondrial GTP Regulates Glucose-Stimulated Insulin Secretion

    OpenAIRE

    Kibbey, Richard G.; Pongratz, Rebecca L.; Romanelli, Anthony J.; Wollheim, Claes B.; Cline, Gary W.; Shulman, Gerald I.

    2007-01-01

    Nucleotide-specific isoforms of the tricarboxylic acid (TCA) cycle enzyme succinyl-CoA synthetase (SCS) catalyze substrate-level synthesis of mitochondrial GTP (mtGTP) and ATP (mtATP). While mtATP yield from glucose metabolism is coupled with oxidative phosphorylation and can vary, each molecule of glucose metabolized within pancreatic beta cells produces approximately one mtGTP, making mtGTP a potentially important fuel signal. In INS-1 832/13 cells and cultured rat islets, siRNA suppression...

  15. Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice

    Science.gov (United States)

    Diaz-Castroverde, Sabela; Gómez-Hernández, Almudena; Fernández, Silvia; García-Gómez, Gema; Di Scala, Marianna; González-Aseguinolaza, Gloria; Fernández-Millán, Elisa; González-Rodríguez, Águeda; García-Bravo, María; Chambon, Pierre; Álvarez, Carmen; Perdomo, Liliana; Beneit, Nuria; Benito, Manuel

    2016-01-01

    ABSTRACT Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte­-specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8 weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus. PMID:27562101

  16. Browning of white adipose tissue uncouples glucose uptake from insulin signaling.

    Directory of Open Access Journals (Sweden)

    Karin Mössenböck

    Full Text Available Presence of thermogenically active adipose tissue in adult humans has been inversely associated with obesity and type 2 diabetes. While it had been shown that insulin is crucial for the development of classical brown fat, its role in development and function of inducible brown-in-white (brite adipose tissue is less clear. Here we show that insulin deficiency impaired differentiation of brite adipocytes. However, adrenergic stimulation almost fully induced the thermogenic program under these settings. Although brite differentiation of adipocytes as well as browning of white adipose tissue entailed substantially elevated glucose uptake by adipose tissue, the capacity of insulin to stimulate glucose uptake surprisingly was not higher in the brite state. Notably, in line with the insulin-independent stimulation of glucose uptake, our data revealed that brite recruitment results in induction of solute carrier family 2 (GLUT-1 expression in adipocytes and inguinal WAT. These results for the first time demonstrate that insulin signaling is neither essential for brite recruitment, nor is it improved in cells or tissues upon browning.

  17. Effect of Iranian Honey bee (Apis Mellifera Venom on Blood Glucose and Insulin in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Seyyedeh Mahbubeh Mousavi

    2012-12-01

    Full Text Available Background: Diabetes is an important disease. This disease is a metabolic disorder characterized by hyperglycemia resulting from perturbation in insulin secretion, insulin action or both. Honey bee venom contains a wide range of polypeptide agents. The principle components of bee venom are mellitin and phospholipase A2. These components increase insulin secretion from the β-cells of pancreas. This study was conducted to show the hypoglycemic effect of honey bee venom on alloxan induced diabetic male rats.Methods: Eighteen adult male rats weighting 200±20 g were placed into 3 randomly groups: control, alloxan monohy­drate-induced diabetic rat and treated group that received honey bee venom daily before their nutrition for four months. Forty eight hours after the last injection, blood was collected from their heart, serum was dissented and blood glucose, insulin, triglyceride and total cholesterol were determined.Results: Glucose serum, triglyceride and total cholesterol level in treated group in comparison with diabetic group was significantly decreased (P< 0.01. On the other hand, using bee venom causes increase in insulin serum in com­parison with diabetic group (P< 0.05.Conclusion: Honeybee venom (apitoxin can be used as therapeutic option to lower blood glucose and lipids in dia­betic rats.

  18. Methylated trivalent arsenicals are potent inhibitors of glucose stimulated insulin secretion by murine pancreatic islets

    Energy Technology Data Exchange (ETDEWEB)

    Douillet, Christelle [Department of Nutrition, Gillings School of Global Public Health, 2302 MHRC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States); Currier, Jenna [Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States); Saunders, Jesse [Department of Nutrition, Gillings School of Global Public Health, 2302 MHRC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States); Bodnar, Wanda M. [Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7431 (United States); Matoušek, Tomáš [Institute of Analytical Chemistry of the ASCR, v.v.i., Veveří 97, 602 00 Brno (Czech Republic); Stýblo, Miroslav, E-mail: styblo@med.unc.edu [Department of Nutrition, Gillings School of Global Public Health, 2302 MHRC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States)

    2013-02-15

    Epidemiologic evidence has linked chronic exposure to inorganic arsenic (iAs) with an increased prevalence of diabetes mellitus. Laboratory studies have identified several mechanisms by which iAs can impair glucose homeostasis. We have previously shown that micromolar concentrations of arsenite (iAs{sup III}) or its methylated trivalent metabolites, methylarsonite (MAs{sup III}) and dimethylarsinite (DMAs{sup III}), inhibit the insulin-activated signal transduction pathway, resulting in insulin resistance in adipocytes. Our present study examined effects of the trivalent arsenicals on insulin secretion by intact pancreatic islets isolated from C57BL/6 mice. We found that 48-hour exposures to low subtoxic concentrations of iAs{sup III}, MAs{sup III} or DMAs{sup III} inhibited glucose-stimulated insulin secretion (GSIS), but not basal insulin secretion. MAs{sup III} and DMAs{sup III} were more potent than iAs{sup III} as GSIS inhibitors with estimated IC{sub 50} ≤ 0.1 μM. The exposures had little or no effects on insulin content of the islets or on insulin expression, suggesting that trivalent arsenicals interfere with mechanisms regulating packaging of the insulin transport vesicles or with translocation of these vesicles to the plasma membrane. Notably, the inhibition of GSIS by iAs{sup III}, MAs{sup III} or DMAs{sup III} could be reversed by a 24-hour incubation of the islets in arsenic-free medium. These results suggest that the insulin producing pancreatic β-cells are among the targets for iAs exposure and that the inhibition of GSIS by low concentrations of the methylated metabolites of iAs may be the key mechanism of iAs-induced diabetes. - Highlights: ► Trivalent arsenicals inhibit glucose stimulated insulin secretion by pancreatic islets. ► MAs{sup III} and DMAs{sup III} are more potent inhibitors than arsenite with IC{sub 50} ∼ 0.1 μM. ► The arsenicals have little or no effects on insulin expression in pancreatic islets. ► The inhibition of

  19. Caffeine's impairment of insulin-mediated glucose disposal cannot be solely attributed to adrenaline in humans

    DEFF Research Database (Denmark)

    Battram, D S; Graham, T E; Dela, F

    2007-01-01

    Caffeine (CAF) impedes insulin-mediated glucose disposal (IMGD) and increases plasma adrenaline concentrations ([ADR]; 0.6 nm). While the antagonism of ADR abolishes the CAF effect, infusion of ADR (0.75 nm) has no effect on IMGD. We have now examined CAF and ADR in concert to determine whether...

  20. Combining insulin pumps and continuous glucose monitors; where are we to go from here?

    NARCIS (Netherlands)

    DeVries, J. Hans

    2008-01-01

    Insulin pump development started in 1978, with the first commercially available glucose sensor marketed in 1999. Combining these two instruments is a logical step toward the closed loop. This article discusses three questions: Is pump development complete? How can a pump and a sensor be combined?

  1. Phase-locking regions in a forced model of slow insulin and glucose oscillations

    DEFF Research Database (Denmark)

    Sturis, Jeppe; Knudsen, Carsten; O'Meara, Niall M.

    1995-01-01

    We present a detailed numerical investigation of the phase-locking regions in a forced model of slow oscillations in human insulin secretion and blood glucose concentration. The bifurcation structures of period 2pi and 4pi tongues are mapped out and found to be qualitatively identical to those of...

  2. Interactions of obesity and glucose-stimulated insulin secretion in familial hypertriglyceridemia.

    Science.gov (United States)

    Maruhama, Y; Abe, R; Okuguchi, F; Oikawa, S; Ohneda, A; Goto, Y

    1978-06-01

    Plasma lipids and lipoproteins, glucose tolerance, plasma insulin response to glucose load, and liver function were examined in 81 relatives of 12 index cases with primary endogenous hypertriglyceridemia, hyperinsulinemia, and hepatic steatosis, as well as in 90 nonrelatives, including the spouses, as controls. Insulin hypersecretion (with or without glucose intolerance), endogenous hypertriglyceridemia, and abnormal liver function suggesting hepatic steatosis were shown to exist in the relatives mostly in combined fashion. Correlation analysis and stepwise multiple regression analysis revealed that the combined disorder developed on the basis of obesity. The incidence of diabetes mellitus was significantly high in the relatives (14.8 per cent) as compared with the normal Japanese population (3.5 per cent). Although the vertical transmission of the combined disorder was noted in almost all pedigrees, the frequency distribution analysis of insulin response, glucose tolerance, and plasma triglyceride showed the histograms of these variables similarly skewed to the right as compared with those of the controls, with no apparent bimodality. In view of the hitherto suggested role of insulin in triglyceride metabolism, it is concluded that hyperinsulinemia coupled with obesity seems to be the basic trait of this form of familial hypertriglyceridemia and hepatic steatosis, though the mode of transmission remains to be elucidated.

  3. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling

    Directory of Open Access Journals (Sweden)

    Nigel Beaton

    2015-11-01

    Conclusions: Collectively, these findings establish TUSC5 as an adipose tissue-specific protein that enables proper protein recycling, linking the ubiquitous vesicle traffic machinery with tissue-specific insulin-mediated glucose uptake into adipose tissue and the maintenance of a healthy metabolic phenotype in mice and humans.

  4. Plasma insulin response to oral glucose tolerance test in type-2 ...

    African Journals Online (AJOL)

    Objective: To study the plasma insulin pattern in type 2 diabetic Nigerians both in the fasting state and in response to a standard oral glucose tolerance test. Design: A cross sectional study. Setting: Diabetic clinic, Ahmadu Bello University Teaching Hospital, Zaria Nigeria. Subjects: Forty type 2 diabetic patients and thirty six ...

  5. Optimizing insulin injection technique and its effect on blood glucose control

    Directory of Open Access Journals (Sweden)

    Giorgio Grassi, MD

    2014-12-01

    Conclusions: Targeted individualized training in IT, including the switch to a 4 mm needle, is associated with improved glucose control, greater satisfaction with therapy, better and simpler injection practices and possibly lower consumption of insulin after only a three month period.

  6. Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats

    DEFF Research Database (Denmark)

    Mikines, K J; Sonne, B; Richter, Erik

    1985-01-01

    The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetize...

  7. Phase-locking regions in a forced model of slow insulin and glucose oscillations

    DEFF Research Database (Denmark)

    Sturis, J.; Knudsen, C.; O'Meara, N.M.

    1996-01-01

    We present a detailed numerical investigation of the phase-locking regions in a forced model of slow oscillations in human insulin secretion and blood glucose concentration. The bifurcation structures of period 2pi and 4pi tongues are mapped out and found to be qualitatively identical to those...

  8. Model of the Glucose-Insulin-Glucagon Dynamics after Subcutaneous Administration of a Glucagon Rescue Bolus in Healthy Humans

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Møller, Jan Kloppenborg; Haidar, Ahmad

    effect of EGP. Ten healthy subjects received a 1 mg subcutaneous (SC) glucagon bolus (GlucaGen®). Plasma samples were collected until 300 minutes post dose and analyzed for glucagon, insulin, and glucose concentrations. All observations were used to fit a physiological model of the glucose......In healthy individuals, insulin and glucagon work in a complex fashion to maintain blood glucose levels within a narrow range. This regulation is distorted in patients with diabetes. The hepatic glucose response due to an elevated glucagon level depends on the current insulin concentration and thus...... endogenous glucose production (EGP) can not be modelled without knowledge of the concentration of both hormones in plasma. Furthermore, literature suggests an upper limit to EGP irrespective of glucagon levels. We build a simulation model of the glucose-insulin-glucagon dynamics in man including saturation...

  9. Non-starch polysaccharides extracted from seaweed can modulate intestinal absorption of glucose and insulin response in the pig.

    Science.gov (United States)

    Vaugelade, P; Hoebler, C; Bernard, F; Guillon, F; Lahaye, M; Duee, P H; Darcy-Vrillon, B

    2000-01-01

    We have investigated the possible effects of algal polysaccharides on postprandial blood glucose and insulin responses in an animal model, the pig. Three seaweed fibres of different viscosities, extracted from Palmaria palmata (PP), Eucheuma cottonii (EC), or Laminaria digitata (LD), were compared to purified cellulose (CEL). Blood glucose and plasma insulin levels were monitored and intestinal absorption quantified for 8 h following a high carbohydrate test-meal supplemented with 5% fibre. Digestive contents were also sampled, 5 h postprandial. As compared to CEL, PP had no effect on glucose and insulin responses. The latter decreased with EC, but glucose absorption balance was not modified. LD addition resulted in a dramatically reduced glucose absorption balance, accompanied by a higher amount of starch left in the small intestine. Among polysaccharides tested, only the highly viscous alginates could affect intestinal absorption of glucose and insulin response.

  10. Alteration of endothelial proteoglycan and heparanase gene expression by high glucose, insulin and heparin.

    Science.gov (United States)

    Han, J; Hiebert, L M

    2013-01-01

    Heparan sulfate proteoglycans (HSPGs) contain a core protein with glycosaminoglycans attached. Reduced glycosaminoglycan, in endothelial HSPGs syndecan and perlecan, is associated with diabetic cardiovascular complications but changes in core protein remain controversial. Since heparanase degrades heparan sulfate, we wished to determine if changes in endothelial heparanase mRNA, by high glucose (HG), correlate with changes in syndecan and perlecan core proteins, and to observe effects of heparin or insulin. RNA was isolated from cultured human aortic endothelial cells treated with HG (30mM), insulin (0.01 units/mL), heparin (0.5μg/mL), HG plus heparin and/or insulin for 24h. Real time PCR revealed that HG alone significantly increased heparanase, decreased syndecan with no effect on perlecan mRNA. Heparin or insulin significantly prevented the increase in heparanase but decreased perlecan mRNA while heparin, but not insulin, prevented the decrease in syndecan mRNA in HG treated cells. HG plus heparin and insulin increased heparanase and syndecan mRNA compared to all other treatments and decreased perlecan mRNA compared to control and HG alone. Heparin may protect endothelium from HG injury by reducing heparanase and increasing syndecan while insulin inhibits heparanase expression. Effects with insulin plus heparin suggest interference in transcriptional regulation of heparanase and syndecan genes. © 2013.

  11. Dissociation of the effects of epinephrine and insulin on glucose and protein metabolism

    International Nuclear Information System (INIS)

    Castellino, P.; Luzi, L.; Del Prato, S.; DeFronzo, R.A.

    1990-01-01

    The separate and combined effects of insulin and epinephrine on leucine metabolism were examined in healthy young volunteers. Subjects participated in four experimental protocols: (1) euglycemic insulin clamp (+80 microU/ml), (2) epinephrine infusion (50 ng.kg-1.min-1) plus somatostatin with basal replacement of insulin and glucagon, (3) combined epinephrine (50 ng.kg-1.min-1) plus insulin (+80 microU/ml) infusion, and (4) epinephrine and somatostatin as in study 2 plus basal amino acid replacement. Studies were performed with a prime-continuous infusion of [1-14C]leucine and indirect calorimetry. Our results indicate that (1) hyperinsulinemia causes a generalized decrease in plasma amino acid concentrations, including leucine; (2) the reduction in plasma leucine concentration is primarily due to an inhibition of endogenous leucine flux; nonoxidative leucine disposal decreases after insulin infusion; (3) epinephrine, without change in plasma insulin concentration, reduces plasma amino acid levels; (4) combined epinephrine-insulin infusion causes a greater decrease in plasma amino levels than observed with either hormone alone; this is because of a greater inhibition of endogenous leucine flux; and (5) when basal amino acid concentrations are maintained constant with a balanced amino acid infusion, epinephrine inhibits the endogenous leucine flux. In conclusion, the present results do not provide support for the concept that epinephrine is a catabolic hormone with respect to amino acid-protein metabolism. In contrast, epinephrine markedly inhibits insulin-mediated glucose metabolism

  12. Effects of high-bran bread on blood glucose control in insulin-dependent diabetic patients.

    Science.gov (United States)

    Nygren, C; Hallmans, G; Lithner, F

    1984-01-01

    The purpose of these studies was to determine whether rye bran, baked into crisp bread (high-bran bread), would affect the blood glucose levels and insulin requirements in insulin-dependent diabetic patients. The high-bran bread was compared with a low-bran bread (series I) and with the usual bread in the patients' diet (series II). The low-bran bread contained 5% dietary fiber, the high-bran bread 18% and the usual bread in the patient's diet 4% as a mean (enzymatic method). In series I five women consumed the low-bran bread for two weeks and then changed to the high-bran bread for four weeks. In series II two men and five women consumed their usual bread during a control period of two weeks and high-bran during the following two weeks. The insulin doses were reduced or the blood glucose concentrations were lowered during the high-bran bread periods.

  13. Closed-Loop Noninvasive Ultrasound Glucose Sensing and Insulin Delivery

    Science.gov (United States)

    2006-09-01

    They have always supported me in my education and I owe my success to them. Esta sequnda tesis es para ustedes y gracias por siempre creer en mi. xi...Glucose monitoring: state of the art and future possibilities,” Medical Engineering Physics, vol.18, no.4, 196, pp.273-288. [21] K. Ogata, Modern

  14. Assessment of glucose, triglycerides and insulin resistance in ...

    African Journals Online (AJOL)

    Background: Malnutrition remains a significant but intriguing consequence of Human immunodeficiency virus (HIV) infection. Besides factors such as decreased food intake and malabsorption, Human immunodeficiency virus infection is typically associated with adverse metabolic events. Aim: We examine the glucose; ...

  15. The SH2B gene is associated with serum leptin and body fat in normal female twins

    NARCIS (Netherlands)

    Jamshidi, Yalda; Snieder, Harold; Ge, Dongliang; Spector, Tim D.; O'Dell, Sandra D.

    Src-homology-2 (SH2)-B, a Janus tyrosine kinase 2-interacting protein, has been identified recently as a key regulator of leptin and insulin sensitivity, glucose homeostasis, and body weight in mice. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the human

  16. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

    Science.gov (United States)

    Qinna, Nidal A; Badwan, Adnan A

    2015-01-01

    Streptozotocin (STZ) is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL), noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents

  17. Insulin sensitivity and beta-cell function in healthy cats: assessment with the use of the hyperglycemic glucose clamp.

    Science.gov (United States)

    Slingerland, L I; Robben, J H; van Haeften, T W; Kooistra, H S; Rijnberk, A

    2007-05-01

    A hyperglycemic clamp (HGC) was developed for use in conscious cats. In 21 healthy, normal glucose tolerant cats glucose disposal rate (M), insulin sensitivity (ISI (HGC)), and beta-cell response (I) at arterial plasma glucose of 9 mmol.l (-1) were measured. The HGC was tolerated well and steady state glucose infusion was achieved. Compared to values reported for humans, M values for the cats were low, which appeared to relate to both a low ISI (HGC) and a low I. HGC measures correlated with fasting plasma glucose and insulin concentrations as well as with their HOMA (homeostasis model assessment) and QUICKI (quantitative insulin sensitivity check index) counterparts. Also, I and ISI (HGC) correlated with their counterparts derived from intravenous glucose tolerance tests. In conclusion, this is the first report of hyperglycemic glucose clamping in cats. The procedure (HGC) allows for measurements of glucose disposal, beta-cell response and insulin sensitivity. Compared to human data, both insulin sensitivity and insulin secretion appeared to be low in cats. This is compatible with the carnivorous nature of this species, for which insulin resistance would be advantageous during periods of restricted food availability.

  18. Impact of taurine depletion on glucose control and insulin secretion in mice.

    Science.gov (United States)

    Ito, Takashi; Yoshikawa, Natsumi; Ito, Hiromi; Schaffer, Stephen W

    2015-09-01

    Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  19. Depressive symptoms and the glucose tolerance test and insulin tolerance test.

    Science.gov (United States)

    Heninger, G R; Mueller, P S; Davis, L S

    1975-12-01

    Patients with severe depression have been observed previously to have a reduced rate of glucose utilization accompanied by elevated serum insulin levels during the intravenous glucose tolerance test (GTT) and a reduced metabolic responsiveness to exogenous insulin during the insulin tolerance test (ITT). These abnormalities were less obvious in patients with neurotic depression as compared to patients with severe endogenous or "psychotic" depression. To evaluate more fully the relationships of depressive symptomatology to these metabolic abnormalities, patients were rated by nursing staff on a short clinical rating scale (SCRS) and by a psychiatrist on the Brief Psychiatric Rating Scale (BPRS) at the time the metabolic measurements were made. Patients were given the GTT and the ITT once when they were off medication and symptomatic and then again 3 to 8 weeks later when symptoms had decreased following amitriptyline treatment. Fasting serum-free fatty acid levels (FFA) had a significant positive correlation to rating of anxiety. Fasting levels of glucose, insulin, and human growth hormone (HGH) did not significantly correlate to any of the ratings. A decreased rate of glucose utilization (k) correlated significantly with increased ratings of motor retardation, emotional withdrawal, and blunt affects, but not to other depressive symptoms. The responsiveness of FFA and HGH during the ITT was significantly less in patients with more severe symptomatology; responsiveness improved when those patients improved. Neither incorrelated to the ratings. These data suggest that within the sydrome of depression, increased FFA is realated to anxiety, decreased glucose utilization is related to motor retardation, emotional withdrawal, and blunt affect, and that decreased FFA and HGH responsiveness to insulin is a nonspecific correlate of the general depressive syndrome.

  20. Insulin induces an increase in cytosolic glucose levels in 3T3-L1 cells with inhibited glycogen synthase activation.

    Science.gov (United States)

    Chowdhury, Helena H; Kreft, Marko; Jensen, Jørgen; Zorec, Robert

    2014-10-02

    Glucose is an important source of energy for mammalian cells and enters the cytosol via glucose transporters. It has been thought for a long time that glucose entering the cytosol is swiftly phosphorylated in most cell types; hence the levels of free glucose are very low, beyond the detection level. However, the introduction of new fluorescence resonance energy transfer-based glucose nanosensors has made it possible to measure intracellular glucose more accurately. Here, we used the fluorescent indicator protein (FLIPglu-600µ) to monitor cytosolic glucose dynamics in mouse 3T3-L1 cells in which glucose utilization for glycogen synthesis was inhibited. The results show that cells exhibit a low resting cytosolic glucose concentration. However, in cells with inhibited glycogen synthase activation, insulin induced a robust increase in cytosolic free glucose. The insulin-induced increase in cytosolic glucose in these cells is due to an imbalance between the glucose transported into the cytosol and the use of glucose in the cytosol. In untreated cells with sensitive glycogen synthase activation, insulin stimulation did not result in a change in the cytosolic glucose level. This is the first report of dynamic measurements of cytosolic glucose levels in cells devoid of the glycogen synthesis pathway.

  1. Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production

    DEFF Research Database (Denmark)

    Lee, Ying Shiuan; De Vadder, Filipe; Tremaroli, Valentina

    2016-01-01

    OBJECTIVE: Insulin-like peptide 5 (INSL5) is a recently identified gut hormone that is produced predominantly by L-cells in the colon, but its function is unclear. We have previously shown that colonic expression of the gene for the L-cell hormone GLP-1 is high in mice that lack a microbiota...... expression in the brain was higher in CONV-R versus GF mice. We also observed that colonic Insl5 expression was suppressed by increasing the energy supply in GF mice by colonization or high-fat feeding. We did not observe any differences in food intake, gut transit or oral glucose tolerance between Insl5......-/- and wild-type mice. However, we showed impaired intraperitoneal glucose tolerance in Insl5-/- mice. We also observed improved insulin tolerance and reduced hepatic glucose production in Insl5-/- mice. CONCLUSIONS: We have shown that colonic Insl5 expression is regulated by the gut microbiota and energy...

  2. Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations

    Directory of Open Access Journals (Sweden)

    Sriskandarajah Nadarajah

    2004-09-01

    Full Text Available Abstract Background Elevated non-esterified fatty acids (NEFA concentrations in non-pregnant animals have been reported to decrease pancreatic responsiveness. As ovine gestation advances, maternal insulin concentrations fall and NEFA concentrations increase. Experiments were designed to examine if the pregnancy-associated rise in NEFA concentration is associated with a reduced pancreatic sensitivity to glucose in vivo. We investigated the possible relationship of NEFA concentrations in regulating maternal insulin concentrations during ovine pregnancy at three physiological states, non-pregnant, non-lactating (NPNL, 105 and 135 days gestational age (dGA, term 147+/- 3 days. Methods The plasma concentrations of insulin, growth hormone (GH and ovine placental lactogen (oPL were determined by double antibody radioimmunoassay. Insulin responsiveness to glucose was measured using bolus injection and hyperglycaemic clamp techniques in 15 non-pregnant, non-lactating ewes and in nine pregnant ewes at 105 dGA and near term at 135 dGA. Plasma samples were also collected for hormone determination. In addition to bolus injection glucose and insulin Area Under Curve calculations, the Mean Plasma Glucose Increment, Glucose Infusion Rate and Mean Plasma Insulin Increment and Area Under Curve were determined for the hyperglycaemic clamp procedures. Statistical analysis of data was conducted with Students t-tests, repeated measures ANOVA and 2-way ANOVA. Results Maternal growth hormone, placental lactogen and NEFA concentrations increased, while basal glucose and insulin concentrations declined with advancing gestation. At 135 dGA following bolus glucose injections, peak insulin concentrations and insulin area under curve (AUC profiles were significantly reduced in pregnant ewes compared with NPNL control ewes (p Conclusions Results suggest that despite an acute suppression of circulating NEFA concentrations during pregnancy, the associated steroids and hormones

  3. Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians12

    Science.gov (United States)

    Fretts, Amanda M; Follis, Jack L; Nettleton, Jennifer A; Lemaitre, Rozenn N; Ngwa, Julius S; Wojczynski, Mary K; Kalafati, Ioanna Panagiota; Varga, Tibor V; Frazier-Wood, Alexis C; Houston, Denise K; Lahti, Jari; Ericson, Ulrika; van den Hooven, Edith H; Mikkilä, Vera; Kiefte-de Jong, Jessica C; Mozaffarian, Dariush; Rice, Kenneth; Renström, Frida; North, Kari E; McKeown, Nicola M; Feitosa, Mary F; Kanoni, Stavroula; Smith, Caren E; Garcia, Melissa E; Tiainen, Anna-Maija; Sonestedt, Emily; Manichaikul, Ani; van Rooij, Frank JA; Dimitriou, Maria; Raitakari, Olli; Pankow, James S; Djoussé, Luc; Province, Michael A; Hu, Frank B; Lai, Chao-Qiang; Keller, Margaux F; Perälä, Mia-Maria; Rotter, Jerome I; Hofman, Albert; Graff, Misa; Kähönen, Mika; Mukamal, Kenneth; Johansson, Ingegerd; Ordovas, Jose M; Liu, Yongmei; Männistö, Satu; Uitterlinden, André G; Deloukas, Panos; Seppälä, Ilkka; Psaty, Bruce M; Cupples, L Adrienne; Borecki, Ingrid B; Franks, Paul W; Arnett, Donna K; Nalls, Mike A; Eriksson, Johan G; Orho-Melander, Marju; Franco, Oscar H; Lehtimäki, Terho; Dedoussis, George V; Meigs, James B; Siscovick, David S

    2015-01-01

    Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049–ln-pmol/L (95% CI: 0.035, 0.063–ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic

  4. The effect of dietary starch level on postprandial glucose and insulin concentrations in cats and dogs.

    Science.gov (United States)

    Hewson-Hughes, Adrian K; Gilham, Matthew S; Upton, Sarah; Colyer, Alison; Butterwick, Richard; Miller, Andrew T

    2011-10-01

    A charge made against feeding dry foods to cats is that the high carbohydrate (i.e. starch) content results in high blood glucose levels which over time may have detrimental health effects. The present study determined the post-meal concentrations of plasma glucose and insulin in adult cats (seven males and four females) and dogs (Labrador retrievers; four males and five females) fed dry diets with low-starch (LS), moderate-starch (MS) or high-starch (HS) levels. In a cross-over design with at least 7 d between the test meals, plasma glucose and insulin concentrations were measured following a single meal of a LS, MS and HS diet (209 kJ/kg bodyweight). Only the HS diet resulted in significant post-meal increases in plasma glucose concentration in cats and dogs although the time-course profiles were different between the species. In cats, plasma glucose concentration was significantly increased above the pre-meal concentration from 11 h until 19 h after the meal, while in dogs, a significant increase above baseline was seen only at the 7 h time point. Plasma insulin was significantly elevated in dogs 4-8 h following the MS diet and 2-8 h after the HS diet. In cats, plasma insulin was significantly greater than baseline from 3-7 and 11-17 h after the HS diet. The time lag (approximately 11 h) between eating the HS diet and the subsequent prolonged elevation of plasma glucose concentration seen in cats may reflect metabolic adaptations that result in a slower digestive and absorptive capacity for complex carbohydrate.

  5. Increased Insulin following an Oral Glucose Load, Genetic Variation near the Melatonin Receptor MTNR1B, but No Biochemical Evidence of Endothelial Dysfunction in Young Asian Men and Women.

    Directory of Open Access Journals (Sweden)

    Maria A Matuszek

    Full Text Available To identify biochemical and genetic variation relating to increased risk of developing type 2 diabetes mellitus and cardiovascular disease in young, lean male and female adults of different ethnicities.Fasting blood and urine and non-fasting blood following oral glucose intake were analysed in 90 Caucasians, South Asians and South East/East Asians.There were no differences in age, birthweight, blood pressure, body mass index, percent body fat, total energy, percentage of macronutrient intake, microalbumin, leptin, cortisol, adrenocorticotropic hormone, nitric oxide metabolites, C-reactive protein, homocysteine, tumor necrosis factor-α, interleukin-6, von Willebrand factor, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and tissue plasminogen activator. Fasting total cholesterol (P = .000, triglycerides (P = .050, low density lipoprotein (P = .009 and non-fasting blood glucose (15 min (P = .024 were elevated in South Asians compared with Caucasians, but there was no significant difference in glucose area under curve (AUC. Non-fasting insulin in South Asians (15-120 min, in South East/East Asians (60-120 min, and insulin AUC in South Asians and South East/East Asians, were elevated compared with Caucasians (P≤0.006. The molar ratio of C-peptide AUC/Insulin AUC (P = .045 and adiponectin (P = .037 were lower in South Asians compared with Caucasians. A significant difference in allele frequency distributions in Caucasians and South Asians was found for rs2166706 (P = 0.022 and rs10830963 (P = 0.009, which are both near the melatonin receptor MTNR1B.Elevated non-fasting insulin exists in young South Asians of normal fasting glucose and insulin. Hepatic clearance of insulin may be reduced in South Asians. No current biochemical evidence exists of endothelial dysfunction at this stage of development. MTNR1B signalling may be a useful therapeutic target in Asian populations in the prevention of type 2 diabetes mellitus.

  6. Enhancement of glomerular filtration rate and renal plasma flow by oral glucose load in well controlled insulin-dependent diabetics

    DEFF Research Database (Denmark)

    Sandahl Christiansen, J; Christensen, C K; Hermansen, K

    1986-01-01

    Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in 27 patients with uncomplicated insulin-dependent diabetes (IDDM) before and after an oral glucose load of 1.1 g glucose/kg body wt. In the 18 patients showing near-normoglycaemia (blood glucose less than or equal to 8 m...

  7. Interaction Between the Central and Peripheral Effects of Insulin in Controlling Hepatic Glucose Metabolism in the Conscious Dog

    Science.gov (United States)

    Ramnanan, Christopher J.; Kraft, Guillaume; Smith, Marta S.; Farmer, Ben; Neal, Doss; Williams, Phillip E.; Lautz, Margaret; Farmer, Tiffany; Donahue, E. Patrick; Cherrington, Alan D.; Edgerton, Dale S.

    2013-01-01

    The importance of hypothalamic insulin action to the regulation of hepatic glucose metabolism in the presence of a normal liver/brain insulin ratio (3:1) is unknown. Thus, we assessed the role of central insulin action in the response of the liver to normal physiologic hyperinsulinemia over 4 h. Using a pancreatic clamp, hepatic portal vein insulin delivery was increased three- or eightfold in the conscious dog. Insulin action was studied in the presence or absence of intracerebroventricularly mediated blockade of hypothalamic insulin action. Euglycemia was maintained, and glucagon was clamped at basal. Both the molecular and metabolic aspects of insulin action were assessed. Blockade of hypothalamic insulin signaling did not alter the insulin-mediated suppression of hepatic gluconeogenic gene transcription but blunted the induction of glucokinase gene transcription and completely blocked the inhibition of glycogen synthase kinase-3β gene transcription. Thus, central and peripheral insulin action combined to control some, but not other, hepatic enzyme programs. Nevertheless, inhibition of hypothalamic insulin action did not alter the effects of the hormone on hepatic glucose flux (production or uptake). These data indicate that brain insulin action is not a determinant of the rapid (<4 h) inhibition of hepatic glucose metabolism caused by normal physiologic hyperinsulinemia in this large animal model. PMID:23011594

  8. Effect of superfused insulin on cerebral cortical glucose utilization in awake goats

    International Nuclear Information System (INIS)

    Pelligrino, D.A.; Miletich, D.J.; Albrecht, R.F.

    1987-01-01

    The effect on cortical cerebral glucose utilization (CMR glu ) of intracerebral insulin administration in awake goats was studied. The insulin was superfused in a mock cerebrospinal fluid (CSF) employing chronically implanted cranial windows. Two windows were implanted bilaterally: one window over an equivalent portion of each parietal cortex. With one window used to deliver insulin/CSF and the other used to simultaneously deliver CSF alone (control), changes in CMR glu were assessed using a modification of a sequential 2-[ 3 H]- then 2[ 14 C]deoxy-D-glucose (2DG) technique originally described by Altenau and Agranoff. Initial experiments employing 125 I-insulin demonstrated that the superfusion procedure increased insulin levels only in the outer 1 mm of cortical tissue exposed to insulin containing perfusate. Additional preliminary evaluations, using conditions known to alter CMR glu , generally established that present methods were adequate to induce and detect CMR glu changes. However, it was also shown experimentally and using a mathematical model that 2-[ 3 H]DG test/control tissue ratios could be influenced by subsequent changes in CMR glu and the dephosphorylation rate. Thus 3 H ratios could not be used to establish preexperimental test/control CMR glu relationships as the originally devised model assumed but could be employed to indicate changes in dephosphorylation. The mathematical model allowed for improved estimates of CMR glu changes from 2[ 14 C]DG/2-[ 3 H]DG test over control tissue ratios. Even with these corrections, insulin was estimated to cause no more than an 8-15% increase in cortical CMR glu . A very limited role for insulin, at least in cerebral cortical metabolic regulation, is thus indicated

  9. Insulin and Glucose Alter Death-Associated Protein Kinase 3 (DAPK3) DNA Methylation in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Mudry, Jonathan M; Lassiter, David G; Nylén, Carolina

    2017-01-01

    of selected genes was determined in muscle from healthy and type 2 diabetic men before and after a glucose tolerance test. Insulin altered DNA methylation in the 3'UTR of the calcium pump ATP2A3 gene. Insulin increased DNA methylation in the gene body of DAPK3, a gene involved in cell proliferation, apoptosis......DNA methylation is altered by environmental factors. We hypothesized DNA methylation is altered in skeletal muscle in response to either insulin or glucose exposure. We performed a genome-wide DNA methylation analysis in muscle from healthy men before and after insulin exposure. DNA methylation...... glucose incorporation to glycogen was unaltered by siRNA against DAPK3, palmitate oxidation was increased. In conclusion, insulin and glucose exposure acutely alter the DNA methylation profile of skeletal muscle, indicating DNA methylation constitutes a rapidly and adaptive epigenetic mark. Furthermore...

  10. Effect of triiodothyronine and insulin on glucose metabolism in tissue explants and isolated adipocytes from lean and obese Zucker rats

    International Nuclear Information System (INIS)

    Bailey, J.W.

    1985-01-01

    Glucose metabolism in adipocytes from 6 week old lean and obese Zucker rats were sensitive to direct and chronic treatment with insulin and triidothyronine (T 3 ). Insulin had a large stimulatory effect on glucose metabolism in acutely isolated adipocytes. This effect was greater in the lean than in the obese. Fatty acid, CO 2 , and glycerol-glyceride formation from radiolabeled glucose was elevated in the obese over the leans. Pretreatment of isolated adipocytes with pharmacological concentrations of T 3 for 30 minutes prior to the measurement of glucose metabolism had a greater effect on lean than obese adipocytes. The presence of insulin was required to observe the acute effects of T 3 . A 2-hour exposure to physiological levels of T 3 in the presence of insulin in both lean and obese adipocytes decreased lipogenesis. In the absence of insulin, a 2 hour pretreatment with physiological levels of T 3 in tissue from a euthyroid animal produced increased lipogenesis

  11. Insulin secretion and incretin hormones after oral glucose in non-obese subjects with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Rask, E; Olsson, T; Söderberg, S

    2004-01-01

    +/- SD] years) and body mass index (BMI; 26.0 +/- 4.0 kg/m(2)) did not differ between the groups. Subjects with IGT displayed lower TIS during the initial 30 minutes after oral glucose (0.97 +/- 0.17 [mean +/- SEM] v 1.75 +/- 0.23 nmol/L in NGT; P =.018) and lower OGIS (397 +/- 21 v 463 +/- 12 mL/min/m(2......); P =.005). The incremental 30-minute TIS times OGIS (reflecting insulin secretion in relation to insulin sensitivity) was significantly reduced in IGT (359 +/- 51 v 774 +/- 91 nmol/min/m(2), P =.001). This measure correlated inversely to the 2-hour glucose level (r = -0.71; P ...). Plasma levels of GLP-1 and GIP increased after oral glucose. Total secretion of these incretin hormones during the 3-hour test did not differ between the 2 groups. However, the 30-minute increase in GLP-1 concentrations was lower in IGT than in NGT (P =.036). We conclude that also in non-obese subjects...

  12. Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle.

    Science.gov (United States)

    Guo, Xiangyu; Yoshitomi, Hisae; Gao, Ming; Qin, Lingling; Duan, Ying; Sun, Wen; Xu, Tunhai; Xie, Peifeng; Zhou, Jingxin; Huang, Liansha; Liu, Tonghua

    2013-03-01

    Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome. Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured. Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles. These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.