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Sample records for acute insulin resistance

  1. Acute pain induces insulin resistance in humans

    DEFF Research Database (Denmark)

    Greisen, J.; Juhl, C.B.; Grøfte, Thorbjørn;

    2001-01-01

    Background: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin. Methods: Ten healthy male volunteers underwent two......, circulating concentrations of glucagon and growth hormone tended to increase during pain. Conclusions: Acute severe pain decreases insulin sensitivity, primarily by affecting nonoxidative glucose metabolism. It is conceivable that the counterregulatory hormonal response plays an important role. This may...

  2. Acute Aerobic Exercise and Plasma Levels of Orexin A, Insulin, Glucose, and Insulin Resistance in Males With Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Alizadeh

    2016-01-01

    Full Text Available Background The endocrine system disruptions are the main factors in metabolic disorders which are due to lifestyle changes, obesity, and aging. Insulin resistance is impaired glucose homeostasis in the presence of insulin and is related to many diseases such as hypertension, coronary artery disease, and type 2 diabetes Objectives This study aimed to investigate the effect of acute aerobic exercise on plasma levels of orexin A, insulin, glucose, and insulin resistance in males with type 2 diabetes. Patients and Methods Twenty subjects (mean age = 45.40 ± 5.42 years, mean weight = 80.91 ± 6.35 kg, body mass index = 25.41 ± 2.76 kg/m2 were randomly assigned into control and experimental groups, involving 10 people in each group. The exercise protocol consisted of one session of acute aerobic exercise on a treadmill at 60% maximal oxygen uptake and the same energy expenditure (300 kcal, which were determined by gas analyzers. Subjects were subjected to samplings before, immediately after, and 24 hours after the acute aerobic exercise. Results The analysis of findings in P ≤ 0.05 indicated that acute aerobic exercise caused a significant increase in plasma levels of orexin A and a significant decrease in plasma levels of glucose immediately after the aerobic activity, but insignificantly affected the plasma levels of insulin and insulin resistance. Conclusions It seems that in people with type 2 diabetes, acute aerobic exercise can decrease the plasma levels of glucose, possibly through increasing orexin A. In addition, negative energy balance is necessary to decrease the levels of insulin and insulin resistance during acute aerobic exercise.

  3. Insulin and Insulin Resistance

    OpenAIRE

    Wilcox, Gisela

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, stru...

  4. Determinants of C-peptide levels and acute insulin resistance/sensitivity in nondiabetic STEMI role of Killip class

    Directory of Open Access Journals (Sweden)

    Chiara Lazzeri

    2014-03-01

    According to our data, the development of acute insulin resistance in the early phase of STEMI can be viewed as an adaptive mechanism to stress (represented by acute myocardial ischemia, similar to other acute critical conditions, related to the severity of stress (that is to the hemodynamic impairment.

  5. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Sylow, Lykke; Fazakerley, Daniel J;

    2014-01-01

    The effect of acute inhibition of both mTORC1 and mTORC2 on metabolism is unknown. A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect. AZD8055...... SIN1 rescued glycolysis. Glucose intolerance following AZD8055 administration was absent in mice lacking the mTORC2 subunit Rictor in muscle, and in vivo glucose uptake into Rictor-deficient muscle was reduced despite normal Akt activity. Taken together, acute mTOR inhibition is detrimental to glucose...

  6. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Sylow, Lykke; Fazakerley, Daniel J.;

    2014-01-01

    The effect of acute inhibition of both mTORC1 and mTORC2 on metabolism is unknown. A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect. AZD8055...... SIN1 rescued glycolysis. Glucose intolerance following AZD8055 administration was absent in mice lacking the mTORC2 subunit Rictor in muscle, and in vivo glucose uptake into Rictor-deficient muscle was reduced despite normal Akt activity. Taken together, acute mTOR inhibition is detrimental to glucose...

  7. Preliminary study on the relationship between insulin resistance and stroke during acute stage

    International Nuclear Information System (INIS)

    Objective: To explore whether there are insulin resistance (IR) in the patients with stroke and the relationship between IR and the patients' condition and prognosis. Method: Fasting plasma glucose (FPG), fasting serum insulin and cortisol levels were determined in 30 patients with cerebral infarction, 31 patients with cerebral hemorrhage and 28 normal adults. The insulin sensitivity index (ISI) was calculated and the result was analyzed by linear correlation with the score of neurologic impairment and the size of lesions. Results: The study showed that the levels of FPG, FINS and cortisol of the patients with stroke were significantly higher than those of the control group (p < 0.001); ISI in patient was significantly lower than that in control group (p < 0.001). There were als significant deference in FPG, FINS levels and ISI between the mild group and moderate as well as severe groups of stroke (p < 0.001, p < 0.01, p < 0.05). ISI was negatively also correlated with area of infarction and volume of haemorrhage (r = -0.372, r -0.406, p < 0.05). It was also negatively correlated with the score of neurologic impairment (r = -0.321, p < 0.05). The mortality rate and the disability rate in moderate and severe groups were higher than those in mild group. Conclusion: There were presence of IR in the patients with stroke. The insulin level and IR during acute stage were correlated with patients condition and prognosis. It was suggested that insulin should be used to treat the patients with presence of IR (high plasma glucose level and low ISI)

  8. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Disease Organizations (PDF, 293 KB). Alternate Language URL Insulin Resistance and Prediabetes Page Content On this page: ... Nutrition Points to Remember Clinical Trials What is insulin? Insulin is a hormone made in the pancreas, ...

  9. Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function?

    DEFF Research Database (Denmark)

    Major-Pedersen, A; Ihlemann, N; Hermann, T S;

    2008-01-01

    The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin....... We found no relationship between postprandial hyperglycemia and post-OGL FMD....

  10. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    M. Langeveld; J.F.M.G. Aerts

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple sphingol

  11. A simple way to identify insulin resistance in non-diabetic acute coronary syndrome patients with impaired fasting glucose

    Directory of Open Access Journals (Sweden)

    Sayantan Ray

    2012-01-01

    Full Text Available Background and Objective: The incidence of coronary artery disease (CAD is increasing in India. Recent data suggesting insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity, or dyslipidemia, so a focus on the relation between acute coronary syndrome (ACS and insulin resistance is relevant. Several studies addressing serum lipoprotein ratios as surrogates for insulin resistance have found promising results. We analyzed the association of lipoprotein ratios with the homeostatic model assessment of insulin resistance (HOMA-IR. Methods: One hundred non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. Admission fasting glucose and insulin concentrations were measured. The HOMA-IR was used to calculate insulin resistance. The fasting serum total cholesterol (TC, triglycerides (TG, and high-density lipoprotein (HDL-C levels are used to calculate following lipid ratios: TC/HDL-C and TG/HDL-C. The areas under the curves (AUC of the receiver operating characteristic curves (ROC were used to compare the power of these serum lipoprotein ratio markers. Results: Lipoprotein ratios were significantly higher in patients with HOMA Index >2 as compared to patients with Index <2. TG/HDL-C ratio and TC/HDL-C ratio were significantly correlated with HOMA-IR (P < 0.05 as obtained by Pearson′s correlation analysis (r = 0.4459, P = 0.0012; r = 0.4815, P = 0.0004; r = 0.3993; P = 0.0041, respectively. The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratios for predicting insulin resistance was 0.80 (95% CI, 0.67-0.93, 0.78 (95% CI, 0.65-0.91, respectively. Conclusion: A plasma TG/HDL-C ratio and TC/HDL-C ratio provide a simple means of identifying insulin resistant and can be used as the markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

  12. Insulin Resistance and Hyperinsulinemia

    OpenAIRE

    Kim, Sun H.; Reaven, Gerald M

    2008-01-01

    OBJECTIVE—Recently, it has been suggested that insulin resistance and hyperinsulinemia can exist in isolation and have differential impacts on cardiovascular disease (CVD). To evaluate this suggestion, we assessed the degree of discordance between insulin sensitivity and insulin response in a healthy, nondiabetic population. RESEARCH DESIGN AND METHODS—Insulin sensitivity was quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 4...

  13. Effect of hepatic glucose production on acute insulin resistance induced by lipid-infusion in awake rats

    Institute of Scientific and Technical Information of China (English)

    Ling Li; Gang-Yi Yang

    2004-01-01

    AIM: To explore the influence of hepatic glucose production on acute insulin resistance induced by a lipid infusion in awake rats.METHODS: A hyperinsulinaemic-euglycaemic clamp was established in awake chronically catheterized rats. Two groups of rats were studied either with a 4-h intraarterial infusion of lipid/heparin or saline. Insulin-mediated peripheral and hepatic glucose metabolism was assessed by hyperinsulinaemiceuglycaemic clamp combined with [3-3H]-glucose infusion.RESULTS: During hyperinsulinaemic-euglycaemic clamp,there was a significant increase in plasma free fatty acid (FFA, from 741.9±50.6 to 2346.4±238.5 μmol/L, P<0.01) in lipid-infused group. The glucose infusion rates (GIR) in the lipid infusion rats, compared to control rats, were significantly reduced (200-240 min average: lipid infusion; 12.6±1.5 vs control; 34.0±1.6 mg/kg.min, P<0.01), declining to - 35%of the corresponding control values during the last time of the clamp (240 min: lipid infusion; 12.0±1.9 vs control;34.7±1.7 mg/kg.min, P<0.0001). At the end of clamp study,the hepatic glucose production (HGP) in control rats was significantly suppressed (88%) from 19.0±4.5 (basal) to 2.3±0.9 mg/kg.min (P<0.01). The suppressive effect of insulin on HGP was significantly blunted in the lipid-infused (P<0.05). The rate of glucose disappearance (GRd) was a slight decrease in the lipid-infused rats compared with controls during the clamp.CONCLUSION: These data suggest that lipid infusion could induces suppression of hepatic glucose production, impairs the abilities of insulin to suppress lipolysis and mediate glucose utilization in peripheral tissue. Therefore, we conclude that lipid-infusion induces an acute insulin resistance in vivo.

  14. Cinnamon intake alleviates the combined effects of dietary-induced insulin resistance and acute stress on brain mitochondria.

    Science.gov (United States)

    Couturier, Karine; Hininger, Isabelle; Poulet, Laurent; Anderson, Richard A; Roussel, Anne-Marie; Canini, Frédéric; Batandier, Cécile

    2016-02-01

    Insulin resistance (IR), which is a leading cause of the metabolic syndrome, results in early brain function alterations which may alter brain mitochondrial functioning. Previously, we demonstrated that rats fed a control diet and submitted to an acute restraint stress exhibited a delayed mitochondrial permeability transition pore (mPTP) opening. In this study, we evaluated the combined effects of dietary and emotional stressors as found in western way of life. We studied, in rats submitted or not to an acute stress, the effects of diet-induced IR on brain mitochondria, using a high fat/high fructose diet (HF(2)), as an IR inducer, with addition or not of cinnamon as an insulin sensitizer. We measured Ca(2+) retention capacity, respiration, ROS production, enzymatic activities and cell signaling activation. Under stress, HF(2) diet dramatically decreased the amount of Ca(2+) required to open the mPTP (13%) suggesting an adverse effect on mitochondrial survival. Cinnamon added to the diet corrected this negative effect and resulted in a partial recovery (30%). The effects related to cinnamon addition to the diet could be due to its antioxidant properties or to the observed modulation of PI3K-AKT-GSK3β and MAPK-P38 pathways or to a combination of both. These data suggest a protective effect of cinnamon on brain mitochondria against the negative impact of an HF(2) diet. Cinnamon could be beneficial to counteract deleterious dietary effects in stressed conditions. PMID:26878796

  15. Insulin Resistance and Hypertension

    Institute of Scientific and Technical Information of China (English)

    张建华; 张春秀

    2002-01-01

    Summary: The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT),impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance(IR) under the disorder of glucose metabolism and hypertension were studied. By glucose toler-ance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucosetolerance curve (AUCG) to area under insulin release curve (AUC1) were calculated and analyzed.The results showed that ISI was decreased to varying degrees in the patients with hypertension,the mildest in the group of NGT with hypertension, followed by the group of IGT without hyper-tension, the group of IGT with hypertension and DM (P=0). There was very significant differ-ence in the ratio of AUCG/AUC1 between the hypertensive patients with NGT and controls (P=0). It was concluded that a significant IR existed during the development of IGT both in hyperten-sion and nonhypertension. The increase of total insulin secretion (AUC1) was associated with non-hypertension simultaneously. IR of the hypertensive patients even existed in NGT and was wors-ened with the deterioration of glucose metabolism disorder, but the AUC1 in the HT groupchanged slightly. A relative deficiency of insulin secretion or dysfunction of β-cell of islet existed inIGT and DM of the hypertensive patients.

  16. Plasma phospholipid transfer protein activity is related to insulin resistance : impaired acute lowering by insulin in obese Type II diabetic patients

    NARCIS (Netherlands)

    Riemens, SC; van Tol, A; Sluiter, WJ; Dullaart, RPF

    1998-01-01

    Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) have important functions in high density lipoprotein (HDL) metabolism. We determined the association of plasma CETP and PLTP activities (measured with exogenous' substrate assays) with insulin resistance, plasma trigl

  17. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Samir Bhattacharya; Debleena Dey; Sib Sankar Roy

    2007-03-01

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, leading to a reduced amount of IR protein in insulin target cells. PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of this important area, emphasizing the current status.

  18. Adipokines and Hepatic Insulin Resistance

    OpenAIRE

    Yu Li; Lin Ding; Waseem Hassan; Daoud Abdelkader; Jing Shang

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarificatio...

  19. Insulin resistance and hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Manuel Romero-Gómez

    2006-01-01

    Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients.Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: "viral" and "metabolic" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American.Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin.Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA ≤ 2 than patients with HOMA > 2. In experiments carried out on Huh-7cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance,steatosis and fibrosis progression.

  20. Admission insulin resistance index in nondiabetic patients with acute coronary syndrome ( clinical and angiographic features

    Directory of Open Access Journals (Sweden)

    Wael Refaie

    2013-01-01

    Conclusion Elevated AIRI can predict coronary artery events in nondiabetic patients with acute chest pain. Multiple coronary vessel involvement is common in such cases and suitable planned invasive therapeutic strategies have to be considered.

  1. Nutritional Modulation of Insulin Resistance

    OpenAIRE

    Weickert, Martin O.

    2012-01-01

    Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM). Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss i...

  2. Hyperglycemia, acute insulin resistance, and renal dysfunction in the early phase of ST-elevation myocardial infarction without previously known diabetes: impact on long-term prognosis.

    Science.gov (United States)

    Lazzeri, Chiara; Valente, Serafina; Chiostri, Marco; Attanà, Paola; Mattesini, Alessio; Nesti, Martina; Gensini, Gian Franco

    2014-11-01

    We evaluated the relationship between admission renal function (as assessed by estimated glomerular filtration rate (eGFR)), hyperglycemia, and acute insulin resistance, indicated by the homeostatic model assessment (HOMA) index, and their impact on long-term prognosis in 825 consecutive patients with ST-elevation myocardial infarction (STEMI) without previously known diabetes who underwent primary percutaneous coronary intervention (PCI). Admission eGFR showed a significant indirect correlation with admission glycemia (Spearman's ρ -0.23, P renal function and glucose values and acute insulin resistance in the early phase of STEMI was detectable, since a significant, indirect correlation between eGFR, insulin values, and glycemia was observed. Patients with renal dysfunction (eGFR renal function (eGFR ≥60 ml/min/1.73 m(2)). The prognostic role of glucose values for 1-year mortality was confined to patients with eGFR ≥60 ml/min/m(2), who represent the large part of our population and are thought to be at lower risk. In these patients, an independent relationship between 1-year mortality and glucose values was detectable not only for admission glycemia but also for glucose values measured at discharge.

  3. Metabolic flexibility and insulin resistance

    OpenAIRE

    Galgani, Jose E.; Moro, Cedric; Ravussin, Eric

    2008-01-01

    Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability. The inability to modify fuel oxidation in response to changes in nutrient availability has been implicated in the accumulation of intramyocellular lipid and insulin resistance. The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this “metabolic inflexibility” i...

  4. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    OpenAIRE

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu; Cao, Wenhong

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative s...

  5. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ...

  6. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... use it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ... also helps a person lose weight control blood glucose levels control blood pressure control cholesterol levels People in the ...

  7. Metabolic flexibility and insulin resistance.

    Science.gov (United States)

    Galgani, Jose E; Moro, Cedric; Ravussin, Eric

    2008-11-01

    Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability. The inability to modify fuel oxidation in response to changes in nutrient availability has been implicated in the accumulation of intramyocellular lipid and insulin resistance. The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this "metabolic inflexibility" is mostly the consequence of impaired cellular glucose uptake. Indeed, after controlling for insulin-stimulated glucose disposal rate (amount of glucose available for oxidation), metabolic flexibility is not altered in obesity regardless of the presence of type 2 diabetes. To understand how intramyocellular lipids accumulate and cause insulin resistance, the assessment of metabolic flexibility to high-fat diets is more relevant than metabolic flexibility during a hyperinsulinemic clamp. An impaired capacity to upregulate muscle lipid oxidation in the face of high lipid supply may lead to increased muscle fat accumulation and insulin resistance. Surprisingly, very few studies have investigated the response to high-fat diets. In this review, we discuss the role of glucose disposal rate, adipose tissue lipid storage, and mitochondrial function on metabolic flexibility. Additionally, we emphasize the bias of using the change in respiratory quotient to calculate metabolic flexibility and propose novel approaches to assess metabolic flexibility. On the basis of current evidence, one cannot conclude that impaired metabolic flexibility is responsible for the accumulation of intramyocellular lipid and insulin resistance. We propose to study metabolic flexibility in response to high-fat diets in individuals having contrasting degree of insulin sensitivity and/or mitochondrial characteristics. PMID:18765680

  8. Nutritional Modulation of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Martin O. Weickert

    2012-01-01

    Full Text Available Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM. Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss is generally difficult to achieve, and distinct metabolic characteristics in patients with T2DM further compromise success. Therefore, investigating the effects of modulating the macronutrient composition of isoenergetic diets is an interesting concept that may lead to additional important insights. Metabolic effects of various different dietary concepts and strategies have been claimed, but results from randomized controlled studies and particularly from longer-term-controlled interventions in humans are often lacking. However, some of these concepts are supported by recent research, at least in animal models and short-term studies in humans. This paper provides an update of the current literature regarding the role of nutrition in the modulation of insulin resistance, which includes the discussion of weight-loss-independent metabolic effects of commonly used dietary concepts.

  9. Obesity genes and insulin resistance

    Science.gov (United States)

    Belkina, Anna C.; Denis, Gerald V.

    2011-01-01

    Purpose of review The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of ‘metabolically healthy but obese’ (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review. Recent findings The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D. Summary Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients. PMID:20585247

  10. Treatment of insulin resistance in uremia.

    Science.gov (United States)

    Stefanović, V; Nesić, V; Stojimirović, B

    2003-02-01

    Insulin resistance is a characteristic feature of uremia. As long as the hyperinsulinemia adequate to overcome the insulin resistance, glucose tolerance remains normal. In patients destined to develop type 2 diabetes, the beta cell compensatory response declines, and relative, or absolute, insulin deficiency develops. At this point glucose intolerance and eventually frank type 2 diabetes occur. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Several studies have confirmed that hemodialysis (HD) treatment significantly improves insulin resistance. Both CAPD and CCPD are shown to improve insulin resistance in uremic patients. Comparing the effect of PD and HD treatment, it was found that the CCPD group has significantly higher insulin sensitivity than the HD group with the CAPD group similar to HD. Treatment of calcium and phosphate disturbances, including vitamin D therapy, significantly reduces insulin resistance in uremia. Treatment with recombinant human erythropoietin (EPO) is an efficient way to increase hematocrit, to reverse cardiovascular problems and to improve insulin sensitivity. Angiotensin-converting enzyme inhibitors have been shown to improve insulin resistance, hyperinsulinemia and glucose intolerance in uremic patients. Thiazolidinediones (TZDs), the new insulin-sensitizing drugs, provide the proof that pharmacologic treatment of insulin resistance can be of enormous clinical benefit. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms. PMID:12653342

  11. Insulin resistance: β-arrestin development

    Institute of Scientific and Technical Information of China (English)

    Joseph T Rodgers; Pere Puigserver

    2009-01-01

    @@ Insulin resistance is simply the in-ability of insulin to elicit a physiologic response. While insulin resistance is most commonly associated with the pathogenesis of metabolic disorders such as type II diabetes and obesity, it is also a predisposing factor to a number of other diseases such as cancer and car-diovascular disease . There are just as many theories as to the cause of insulin resistance as there are insulin signal-ing molecules and it is very unclear as to which are the actual molecular mechanisms of insulin resistance in diseased states.

  12. Mitochondrial efficiency and insulin resistance.

    Science.gov (United States)

    Crescenzo, Raffaella; Bianco, Francesca; Mazzoli, Arianna; Giacco, Antonia; Liverini, Giovanna; Iossa, Susanna

    2014-01-01

    Insulin resistance, "a relative impairment in the ability of insulin to exert its effects on glucose, protein and lipid metabolism in target tissues," has many detrimental effects on metabolism and is strongly correlated to deposition of lipids in non-adipose tissues. Mitochondria are the main cellular sites devoted to ATP production and fatty acid oxidation. Therefore, a role for mitochondrial dysfunction in the onset of skeletal muscle insulin resistance has been proposed and many studies have dealt with possible alteration in mitochondrial function in obesity and diabetes, both in humans and animal models. Data reporting evidence of mitochondrial dysfunction in type two diabetes mellitus are numerous, even though the issue that this reduced mitochondrial function is causal in the development of the disease is not yet solved, also because a variety of parameters have been used in the studies carried out on this subject. By assessing the alterations in mitochondrial efficiency as well as the impact of this parameter on metabolic homeostasis of skeletal muscle cells, we have obtained results that allow us to suggest that an increase in mitochondrial efficiency precedes and therefore can contribute to the development of high-fat-induced insulin resistance in skeletal muscle. PMID:25601841

  13. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

    the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...... hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...

  14. Fatty acid-induced insulin resistance

    DEFF Research Database (Denmark)

    Le Marchand-Brustel, Y; Gual, P; Grémeaux, T;

    2003-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterized by a decrease in the insulin effect on glucose transport in muscle and adipose tissue. Tyrosine phosphorylation of IRS-1 (insulin receptor...... substrate 1) and its binding to PI 3-kinase (phosphoinositide 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Various studies have implicated lipids as a cause of insulin resistance in muscle. Elevated plasma fatty acid concentrations...... are associated with reduced insulin-stimulated glucose transport activity as a consequence of altered insulin signalling through PI 3-kinase. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose...

  15. Differential impact of acute high-intensity exercise on circulating endothelial microparticles and insulin resistance between overweight/obese males and females.

    Directory of Open Access Journals (Sweden)

    Cody Durrer

    Full Text Available An acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE to high-intensity interval exercise (HIIE on circulating endothelial microparticles (EMPs and insulin sensitivity in overweight/obese men and women.Inactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6 and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7 participated in three experimental trials in a randomized counterbalanced crossover design: 1 No exercise control (Control; 2 HICE (20 min cycling @ just above ventilatory threshold; 3 HIIE (10 X 1-min @ ∼ 90% peak aerobic power. Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼ 18 hr after each condition. CD62E(+ and CD31(+/CD42b- EMPs were assessed by flow cytometry and insulin resistance (IR was estimated by homeostasis model assessment (HOMA-IR.There was a significant sex X exercise interaction for CD62E(+ EMPs, CD31(+/CD42b- EMPs, and HOMA-IR (all P < 0.05. In males, both HICE and HIIE reduced EMPs compared to Control (P ≤ 0.05. In females, HICE increased CD62E(+ EMPs (P < 0.05 vs. Control whereas CD31(+/CD42b- EMPs were unaltered by either exercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (P<0.05.Overweight/obese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E(+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females.

  16. Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans

    OpenAIRE

    Halperin, Florencia; Lopez, Ximena; Manning, Raquel; Kahn, C. Ronald; Kulkarni, Rohit Narayan; Goldfine, Allison Braunwald

    2012-01-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic β-cell dysfunction, the latter possibly caused by a defect in insulin signaling in β-cells. We hypothesized that insulin’s effect to potentiate glucose-stimulated insulin secretion (GSIS) would be diminished in insulin-resistant persons. To evaluate the effect of insulin to modulate GSIS in insulin-resistant compared with insulin-sensitive subjects, 10 participants with impaired glucose tolerance (IGT), 11 with T2D, a...

  17. Insulin resistance and Alzheimer’s disease

    OpenAIRE

    de la Monte, Suzanne M.

    2009-01-01

    Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer’s disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second maj...

  18. Role of Mitochondrial Dysfunction in Insulin Resistance

    OpenAIRE

    Kim, Jeong-a; Wei, Yongzhong; Sowers, James R.

    2008-01-01

    Insulin resistance is characteristic of obesity, type 2 diabetes, and components of the cardiometabolic syndrome, including hypertension and dyslipidemia, that collectively contribute to a substantial risk for cardiovascular disease. Metabolic actions of insulin in classic insulin target tissues (eg, skeletal muscle, fat, and liver), as well as actions in nonclassic targets (eg, cardiovascular tissue), help to explain why insulin resistance and metabolic dysregulation are central in the patho...

  19. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  20. Adipose Inflammation, Insulin Resistance, and Cardiovascular Disease

    OpenAIRE

    Shah, Arti; Mehta, Nehal; Reilly, Muredach P.

    2008-01-01

    Adiposity-associated inflammation and insulin resistance are strongly implicated in the development of type 2 diabetes and atherosclerotic cardiovascular disease. This article reviews the mechanisms of adipose inflammation, because these may represent therapeutic targets for insulin resistance and for prevention of metabolic and cardiovascular consequences of obesity. The initial insult in adipose inflammation and insulin resistance, mediated by macrophage recruitment and endogenous ligand ac...

  1. Insulin Resistance: From Theory To Practice

    Directory of Open Access Journals (Sweden)

    Srinivas Kakkilaya Bevinje

    2006-07-01

    Full Text Available Insulin resistance is at the core of the well recognised metabolic syndrome and possibly many other ailments commonly seen in the modern society. While the quantification of insulin resistance remains a difficult task, the problems associated with it are increasing in epidemic proportions. Need of the hour therefore is to develop concise dietary and pharmacological guidelines for for prevention and management of insulin resistance

  2. Antibody against the insulin receptor causes disappearance of insulin receptors in 3T3-L1 cells: a possible explanation of antibody-induced insulin resistance.

    OpenAIRE

    Grunfeld, C.

    1984-01-01

    The effect of a rabbit antibody induced against the rat insulin receptor (RAR) was tested using cultured 3T3-L1 fat cells. As previously seen with antibodies against the insulin receptor from patients with the type B syndrome of insulin resistance and acanthosis nigricans, RAR acutely mimicked the action of insulin by stimulating deoxyglucose uptake. After prolonged exposure of 3T3-L1 cells to RAR, insulinomimetic activity was lost and the cells became resistant to the action of insulin. This...

  3. Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance.

    Science.gov (United States)

    McNay, Ewan C; Ong, Cecilia T; McCrimmon, Rory J; Cresswell, James; Bogan, Jonathan S; Sherwin, Robert S

    2010-05-01

    Insulin regulates glucose uptake and storage in peripheral tissues, and has been shown to act within the hypothalamus to acutely regulate food intake and metabolism. The machinery for transduction of insulin signaling is also present in other brain areas, particularly in the hippocampus, but a physiological role for brain insulin outside the hypothalamus has not been established. Recent studies suggest that insulin may be able to modulate cognitive functions including memory. Here we report that local delivery of insulin to the rat hippocampus enhances spatial memory, in a PI-3-kinase dependent manner, and that intrahippocampal insulin also increases local glycolytic metabolism. Selective blockade of endogenous intrahippocampal insulin signaling impairs memory performance. Further, a rodent model of type 2 diabetes mellitus produced by a high-fat diet impairs basal cognitive function and attenuates both cognitive and metabolic responses to hippocampal insulin administration. Our data demonstrate that insulin is required for optimal hippocampal memory processing. Insulin resistance within the telencephalon may underlie the cognitive deficits commonly reported to accompany type 2 diabetes.

  4. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  5. Insulin resistance and maximal oxygen uptake

    DEFF Research Database (Denmark)

    Seibaek, Marie; Vestergaard, Henrik; Burchardt, Hans;

    2003-01-01

    Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown.......Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown....

  6. Insulin resistance and diabetes in HIV infection.

    Science.gov (United States)

    Das, Satyajit

    2011-09-01

    Insulin resistance is an important and under recognized consequence of HIV treatment. Different studies have yielded widely varying estimates of the prevalence of impaired glucose metabolism in people on highly active antiretroviral therapy (HAART). The risk increases further with hepatitis C co infection. Although Protease inhibitors (PIs) are the main drug class implicated in insulin resistance, some studies have shown an association of increased risk of diabetes with cumulative exposure of nucleoside reverse transcriptase inhibitors (NRTIs). The effect of switching to other antiretrovirals has not been fully determined and the long-term consequences of insulin resistance in this population are not known. Treatment of established diabetes mellitus should generally follow existing guidelines. It is therefore reasonable to recommend general measures to increase insulin sensitivity in all patients infected with HIV, such as regular aerobic exercise and weight reduction for overweight persons. The present review article has the information of some recent patents regarding the insulin resistance in HIV infection. PMID:21824074

  7. LINK BETWEEN OXIDATIVE STRESS AND INSULIN RESISTANCE

    Institute of Scientific and Technical Information of China (English)

    Lan-fang Li; Jian Li

    2007-01-01

    Many studies on oxidative stress, insulin resistance, and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states. Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress. And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance. However, negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications. Furthermore, it appears that oxidative stress is only one of the factors contributing to diabetic complications. Thus, antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.

  8. Selective insulin resistance in hepatocyte senescence

    International Nuclear Information System (INIS)

    Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance

  9. Selective insulin resistance in hepatocyte senescence

    Energy Technology Data Exchange (ETDEWEB)

    Aravinthan, Aloysious [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Challis, Benjamin [Institute of Metabolic Sciences, University of Cambridge, Cambridge (United Kingdom); Shannon, Nicholas [Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Hoare, Matthew [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Heaney, Judith [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Foundation for Liver Research, Institute of Hepatology, London (United Kingdom); Alexander, Graeme J.M., E-mail: gja1000@doctors.org.uk [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom)

    2015-02-01

    Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance.

  10. [Insulin resistance - its causes and therapy possibilities].

    Science.gov (United States)

    Pelikánová, Terezie

    2014-09-01

    Insulin resistance (IR) is defined as a condition where normal plasma free insuconcentrations induce a reduced response of the body. In the narrower sense we understand IR as the impairment of insulin action in the target structure which may arise at any level of the insulin signalling cascade. In the clinical conditions we usually define it as the impairment of insulin action in glucose metabolism, although it is true that the impairment may concern different effects of insulin and different cell structures. The characteristic feature of IR linked to the metabolic syndrome or Type 2 diabetes is defective signalling which affects PI3-kinase branch of insulin signalling cascade. Other insulin actions depending on the signalling through the Ras complex and MAP-kinase, may not be affected. Due to compensatory hyperinsulinemia they may be even increased. The article summarizes some recent findings regarding the structure and regulation of insulin signalling cascade and analyses selected primary and secondary causes of IR which include genetic and epigenetic factors, the microRNA regulation role, metabolic, humoral and immunological factors. The detailed knowledge of the causes of IR opens possibilities of its rational treatment. This is currently based on the treatment of curable causes of IR, i.e. consistent compensation of diabetes, weight reduction, regimen arrangements (diet, physical activity), re-assessment of the need to use corticosteroids in therapy, treatment of coexisting conditions and possibly administration of metformin or pioglitazone.Key words: cytokines - insulin resistance - insulin signalling cascade. PMID:25294764

  11. A novel surrogate index for hepatic insulin resistance.

    LENUS (Irish Health Repository)

    Vangipurapu, J

    2011-03-01

    In epidemiological and genetic studies surrogate indices are needed to investigate insulin resistance in different insulin-sensitive tissues. Our objective was to develop a surrogate index for hepatic insulin resistance.

  12. Ghrelin- and GH-induced insulin resistance

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Krag, Morten B; Poulsen, Morten M;

    2013-01-01

    Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects....

  13. Mechanisms Linking Inflammation to Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Li Chen

    2015-01-01

    Full Text Available Obesity is now widespread around the world. Obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, which makes obesity a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by overnutrition which leads to lipid accumulation in adipocytes. Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuation of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance. In this paper, we discuss how these factors and signaling pathways contribute to insulin resistance and the therapeutic promise targeting inflammation in insulin resistance based on the latest experimental studies.

  14. Managing insulin resistance: role of liraglutide

    OpenAIRE

    Kalra, Sanjay

    2010-01-01

    Sanjay Kalra1, Bharti Kalra1, Satish Kumar2, Amit Sharma11Department of Endocrinology, Bharti Hospital, Karnal, India; 2Department of Clinical Operations, Excel Life Sciences, Noida, IndiaAbstract: Diabetes mellitus is part of the insulin resistance syndrome, which includes hypertension, dyslipidemia, and obesity as its other components. Conversely, insulin resistance is a major pathophysiologic factor in the development of type 2 diabetes. It makes sense, therefore, to choose an anti-diabeti...

  15. Hypoadiponectinemia in Obesity: Association with Insulin Resistance

    OpenAIRE

    Prakash, Jai; Mittal, Balraj; Awasthi, Shally; Agarwal, C.G.; Srivastava, Neena

    2012-01-01

    Obesity is risk factor for insulin resistance, diabetes, and other chronic diseases. Adiponectin, an adipose-specific protein with antiatherogenic and antiinflammatory effects, were found to be associated with obesity, type 2 diabetes, and insulin resistance. Our aim to identify possible relationships between circulating adiponectin and obesity as well as obesity related phenotypes. A total of 642, obese and non-obese individuals were included in this cross-sectional study. Hormone and glucos...

  16. High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Li Zhi

    Full Text Available Clinical studies have shown hyperuricemia strongly associated with insulin resistance as well as cardiovascular disease. Direct evidence of how high uric acid (HUA affects insulin resistance in cardiomyocytes, but the pathological mechanism of HUA associated with cardiovascular disease remains to be clarified. We aimed to examine the effect of HUA on insulin sensitivity in cardiomyocytes and on insulin resistance in hyperuricemic mouse model. We exposed primary cardiomyocytes and a rat cardiomyocyte cell line, H9c2 cardiomyocytes, to HUA, then quantified glucose uptake with a fluorescent glucose analog, 2-NBDG, after insulin challenge and detected reactive oxygen species (ROS production. Western blot analysis was used to examine the levels of insulin receptor (IR, phosphorylated insulin receptor substrate 1 (IRS1, Ser307 and phospho-Akt (Ser473. We monitored the impact of HUA on insulin resistance, insulin signaling and IR, phospho-IRS1 (Ser307 and phospho-Akt levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment. HUA inhibited insulin-induced glucose uptake in H9c2 and primary cardiomyocytes. It increased ROS production; pretreatment with N-acetyl-L-cysteine (NAC, a ROS scavenger, reversed HUA-inhibited glucose uptake induced by insulin. HUA exposure directly increased the phospho-IRS1 (Ser307 response to insulin and inhibited that of phospho-Akt in H9C2 cardiomyocytes, which was blocked by NAC. Furthermore, the acute hyperuricemic mice model showed impaired glucose tolerance and insulin tolerance accompanied by increased phospho-IRS1 (Ser307 and inhibited phospho-Akt response to insulin in myocardial tissues. HUA inhibited insulin signaling and induced insulin resistance in cardiomyocytes in vitro and in vivo, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease.

  17. Patients with psoriasis are insulin resistant

    DEFF Research Database (Denmark)

    Gyldenløve, Mette; Storgaard, Heidi; Holst, Jens Juul;

    2015-01-01

    BACKGROUND: Patients with psoriasis have increased risk of type 2 diabetes. The pathophysiology is largely unknown, but it is hypothesized that systemic inflammation causes insulin resistance. Insulin sensitivity has only been sparsely investigated in patients with psoriasis, and previous studies...... have used suboptimal methodology. The hyperinsulinemic euglycemic clamp remains the gold standard for quantifying whole-body insulin sensitivity. OBJECTIVE: We sought to investigate if normal glucose-tolerant patients with psoriasis exhibit impaired insulin sensitivity. METHODS: Three....... Mean ± SEM psoriasis duration was 23 ± 3 years and Psoriasis Area and Severity Index score was 12.7 ± 1.4. Patients with psoriasis exhibited reduced insulin sensitivity compared with control subjects (median M-value 4.5 [range 1.6-14.0] vs 7.4 [range 2.1-10.8] mg/kg/min, P = .046). There were...

  18. Nonalcoholic steatohepatitis and insulin resistance in children

    Institute of Scientific and Technical Information of China (English)

    Mikage; Arata; Junya; Nakajima; Shigeo; Nishimata; Tomomi; Nagata; Hisashi; Kawashima

    2014-01-01

    Various pathological conditions can cause fatty liver in children. Nonalcoholic steatohepatitis(NASH) in children has been known since 1983. However, NASH diagnosed in childhood does not have a favorable outcome.The pathological characteristics of NASH are significantly different between children and adults. Nonalcoholic fatty liver disease(NAFLD)/NASH is accompanied by insulin resistance, which plays a pivotal role in its pathophysiology in both children and adults. In NASH,a “two-hit” model involving triglyceride accumulation(first hit) and liver damage(second hit) has been accepted. Insulin resistance was found to correlate with changes in fat levels; however, it did not correlate with fibrosis or NAFLD activity score in children. Therefore,insulin resistance may be important in the first hit.Because there is obvious familial clustering in NASH,genetic predisposition as well as environmental factors including diet might be the second hit of NAFLD/NASH.

  19. Chemokine Systems Link Obesity to Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Tsuguhito Ota

    2013-06-01

    Full Text Available Obesity is a state of chronic low-grade systemic inflammation. This chronic inflammation is deeply involved in insulin resistance, which is the underlying condition of type 2 diabetes and metabolic syndrome. A significant advance in our understanding of obesity-associated inflammation and insulin resistance has been recognition of the critical role of adipose tissue macrophages (ATMs. Chemokines are small proteins that direct the trafficking of immune cells to sites of inflammation. In addition, chemokines activate the production and secretion of inflammatory cytokines through specific G protein-coupled receptors. ATM accumulation through C-C motif chemokine receptor 2 and its ligand monocyte chemoattractant protein-1 is considered pivotal in the development of insulin resistance. However, chemokine systems appear to exhibit a high degree of functional redundancy. Currently, more than 50 chemokines and 18 chemokine receptors exhibiting various physiological and pathological properties have been discovered. Therefore, additional, unidentified chemokine/chemokine receptor pathways that may play significant roles in ATM recruitment and insulin sensitivity remain to be fully identified. This review focuses on some of the latest findings on chemokine systems linking obesity to inflammation and subsequent development of insulin resistance.

  20. Acute knockdown of the insulin receptor or its substrates Irs1 and 2 in 3T3-L1 adipocytes suppresses adiponectin production

    OpenAIRE

    Groeneveld, Matthijs P; Brierley, Gemma V.; Rocha, Nuno M.; Kenneth Siddle; Semple, Robert K.

    2016-01-01

    Loss of function of the insulin receptor (INSR) in humans produces severe insulin resistance. Unlike “common” insulin resistance, this is associated with elevated plasma levels of the insulin-sensitising, adipose-derived protein adiponectin. The underlying mechanism for this paradox is unclear, and it is at odds with the acute stimulation of adiponectin secretion reported on insulin treatment of cultured adipocytes. Given recent evidence for ligand-independent actions of the INSR, we used a l...

  1. Role of resistin in diet-induced hepatic insulin resistance

    OpenAIRE

    Muse, Evan D.; Obici, Silvana; Bhanot, Sanjay; Monia, Brett P.; McKay, Robert A.; Rajala, Michael W.; Scherer, Philipp E.; Rossetti, Luciano

    2004-01-01

    Resistin is an adipose-derived hormone postulated to link adiposity to insulin resistance. To determine whether resistin plays a causative role in the development of diet-induced insulin resistance, we lowered circulating resistin levels in mice by use of a specific antisense oligodeoxynucleotide (ASO) directed against resistin mRNA and assessed in vivo insulin action by the insulin-clamp technique. After 3 weeks on a high-fat (HF) diet, mice displayed severe insulin resistance associated wit...

  2. 急性颅脑损伤后胰岛素抵抗、血清IL-6的相关性研究%Relationship of insulin resistance and IL-6 after acute brain injury

    Institute of Scientific and Technical Information of China (English)

    陈耀隆; 何朝晖; 刘浏

    2013-01-01

    目的 探讨不同程度、不同时间段急性颅脑损伤患者血糖、胰岛素水平关系及血清白细胞介素-6(IL-6)的含量变化及临床意义.方法 106例急性颅脑损伤患者按入院时GCS评分分为轻度、中度和重度3组,分别于伤后1、2、3、4、5 d测定空腹血糖、血清胰岛素值并计算胰岛素抵抗指数(HOMA-IR),分析急性颅脑损伤程度与HOMA-IR之间关系;采用酶联免疫吸附(ELISA)法测定血清IL-6含量,根据IL-6的动态变化,分析急性颅脑损伤程度与血清IL-6含量之间关系.结果 不同程度的急性颅脑损伤患者血糖、胰岛素水平及HOMA-IR比较差异有统计学意义(P<0.05),血糖、血清胰岛素和HOMA-IR越高,急性颅脑损伤的程度越重,同时血清IL-6含量在伤后高于对照组(P<0.05),而在重型颅脑损伤中增高较轻型和中型颅脑损伤更为明显(P<0.05).结论 空腹血糖值、HOMA-IR及血清IL-6含量与急性颅脑损伤程度存在相关性,可作为评估急性颅脑损伤严重程度及预后的一个客观指标.%Objective Analysis of acute brain injury in different degree and different period of time of blood glucose, insulin levels and the relationship between the serum levels of interleukin 6 (IL-6) content change and its clinical significance. Methods 106 cases of acute brain injury patients according to their GCS scores were divided into mild, moderate and severe group three, respectively, after injury in ID, 2D, 3D, 4D, 5D determination of fasting blood glucose, serum insulin values and calculated the insulin resistance index (HOMA-IR), analysis of acute craniocerebral injury degree and the relationship between HOM A-IR; using enzyme ELISA (ELISA ) method for the determination of the content of serum IL-6, according to the dynamic changes of IL-6, analysis of a-cute head injury severity and the content of serum IL-6 relationship. Results Different degree of acute craniocerebral injury patients blood glucose, insulin

  3. Serum acylated ghrelin is negatively correlated with the insulin resistance in the CODING study.

    Directory of Open Access Journals (Sweden)

    Peyvand Amini

    Full Text Available OBJECTIVE: Ghrelin is a 28-amino acid orexigenic peptide synthesized mainly in the stomach. Acute administration of ghrelin has been found to decrease insulin secretion. However, little data is available regarding whether ghrelin contributes to the long-term regulation of insulin resistance at the population level. The aim of this study is to investigate the association between circulating ghrelin and insulin resistance in a large population based study. DESIGN: A total of 2082 CODING study (Complex Diseases in the Newfoundland population: Environment and Genetics subjects were assessed. Subjects were of at least third generation Newfoundland descent, between the ages of 20 and 79 years, and had no serious metabolic, cardiovascular, or endocrine diseases. Ghrelin was measured with an Enzyme Immunoassay method. Insulin and fasting glucose were measured by Immulite 2500 autoanalyzer and Lx20 clinical chemistry analyzer, respectively. Homeostatic Model Assessment of β cell function (HOMA-β and Insulin Resistance (HOMA-IR and Quantitative Insulin-sensitivity Check Index (QUICKI were used for measurement of insulin resistance. RESULTS: Partial correlation analyses showed a significant negative correlation between circulating ghrelin and insulin level and insulin resistance in the entire cohort and also in men and women separately. The aforementioned correlation was independent of age, percentage of trunk fat and HDL-cholesterol. According to menopausal status, only pre-menopausal women revealed negative correlations. CONCLUSION: Our results suggest that except for postmenopausal women, high circulating ghrelin level is associated with lower insulin resistance in the general population.

  4. Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

    Institute of Scientific and Technical Information of China (English)

    Takumi; Kawaguchi; Michio; Sata

    2010-01-01

    Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indic...

  5. Epigenetic markers to further understand insulin resistance.

    Science.gov (United States)

    Ling, Charlotte; Rönn, Tina

    2016-11-01

    Epigenetic variation in human adipose tissue has been linked to type 2 diabetes and its related risk factors including age and obesity. Insulin resistance, a key risk factor for type 2 diabetes, may also be associated with altered DNA methylation in visceral and subcutaneous adipose tissue. Furthermore, linking epigenetic variation in target tissues to similar changes in blood cells may identify new blood-based biomarkers. In this issue of Diabetologia, Arner et al studied the transcriptome and methylome in subcutaneous and visceral adipose tissue of 80 obese women who were either insulin-sensitive or -resistant (DOI 10.1007/s00125-016-4074-5 ). While they found differences in gene expression between the two groups, no alterations in DNA methylation were found after correction for multiple testing. Nevertheless, based on nominal p values, their methylation data overlapped with methylation differences identified in adipose tissue of individuals with type 2 diabetes compared with healthy individuals. Differential methylation of these overlapping CpG sites may predispose to diabetes by occurring already in the insulin-resistant state. Furthermore, some methylation changes may contribute to an inflammatory process in adipose tissue since the identified CpG sites were annotated to genes encoding proteins involved in inflammation. Finally, the methylation pattern in circulating leucocytes did not mirror the adipose tissue methylome of these 80 women. Together, identifying novel molecular mechanisms contributing to insulin resistance and type 2 diabetes may help advance the search for new therapeutic alternatives. PMID:27650286

  6. Insulin resistance, steatosis and hepatitis C virus

    OpenAIRE

    Mangia, Alessandra; Ripoli, Maria

    2013-01-01

    Epidemiological studies have shown an increased occurrence of metabolic disorders such as insulin resistance (IR) and steatosis in patients with hepatitis C virus (HCV) infection. IR is believed to represent one of the central clinical features of the “metabolic syndrome” and the major pathogenetic factor for type 2 diabetes mellitus. In patients with chronic HCV hepatitis, IR may have several dangerous consequences such as accelerated progression of liver fibrosis, resistance to antiviral th...

  7. Interleukin-10 Prevents Diet-Induced Insulin Resistance by Attenuating Macrophage and Cytokine Response in Skeletal Muscle

    OpenAIRE

    Hong, Eun-Gyoung; Ko, Hwi Jin; Cho, You-Ree; Kim, Hyo-Jeong; Ma, Zhexi; Yu, Tim Y.; Friedline, Randall H; Kurt-Jones, Evelyn; Finberg, Robert; Matthew A Fischer; Granger, Erica L.; Norbury, Christopher C.; Hauschka, Stephen D.; Philbrick, William M.; Lee, Chun-Geun

    2009-01-01

    OBJECTIVE Insulin resistance is a major characteristic of type 2 diabetes and is causally associated with obesity. Inflammation plays an important role in obesity-associated insulin resistance, but the underlying mechanism remains unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine with lower circulating levels in obese subjects, and acute treatment with IL-10 prevents lipid-induced insulin resistance. We examined the role of IL-10 in glucose homeostasis using transgenic mice with m...

  8. Advances in TCM Research of Insulin Resistance

    Institute of Scientific and Technical Information of China (English)

    尚文斌; 程海波

    2001-01-01

    @@Insulin resistance (IR) refers to subnormal response to a certain amount of insulin and is the most characteristic phenomenon in non-insulin dependent diabetes mellitus (NIDDM). It is also an element of the pathogenic mechanism shared with obesity, systemic hypertension, abnormal lipid metabolism and atherosclerosis. In recent years, studies on its treatment with traditional Chinese medicine (TCM) have gradually been carried out and the following is a report of them. Mechanisms of Diabetic IR in TCM Terms Action of insulin antagonizing hormones in peripheral tissues is one of the causes of diabetic IR. Cyclic nucleosides cAMP and cGMP, important intracellular messengers, are considered to be the second messenger of insulin, and cAMP is related to the amount of insulin receptors. Early in 1980s, some authors investigated the relationship among the symptoms of diabetes and such hormones and cAMP/cGMP ratio. Although they did not give due attention to IR, their studies provided evidences for differentiation of symptoms and signs in IR typing.

  9. Adipokines mediate inflammation and insulin resistance

    Directory of Open Access Journals (Sweden)

    Jeffrey E. Pessin

    2013-06-01

    Full Text Available For many years, adipose tissue was considered as an inert energy storage organ that accumulates and stores triacylglycerols during energy excess and releases fatty acids in times of systemic energy need. However, over the last two decades adipose tissue depots have been established as highly active endocrine and metabolically important organs that modulate energy expenditure and glucose homeostasis. In rodents, brown adipose tissue plays an essential role in non-shivering thermogenesis and in energy dissipation that can serve to protect against diet-induced obesity. White adipose tissue collectively referred too as either subcutaneous or visceral adipose tissue is responsible for the secretion of an array of signaling molecules, termed adipokines. These adipokines function as classic circulating hormones to communicate with other organs including brain, liver, muscle, the immune system and adipose tissue itself. The dysregulation of adipokines has been implicated in obesity, type 2 diabetes and cardiovascular disease. Recently, inflammatory responses in adipose tissue have been shown as a major mechanism to induce peripheral tissue insulin resistance. Although leptin and adiponectin regulate feeding behavior and energy expenditure, these adipokines are also involved in the regulation of inflammatory responses. Adipose tissue secrete various pro- and anti-inflammatory adipokines to modulate inflammation and insulin resistance. In obese humans and rodent models, the expression of pro-inflammatory adipokines is enhanced to induce insulin resistance. Collectively, these findings have suggested that obesity-induced insulin resistance may result, at least in part, from an imbalance in the expression of pro- and anti-inflammatory adipokines. Thus we will review the recent progress regarding the physiological and molecular functions of adipokines in the obesity-induced inflammation and insulin resistance with perspectives on future directions.

  10. Molecular Mechanisms of Insulin Resistance Development

    Directory of Open Access Journals (Sweden)

    Vsevolod Arsen'evich Tkachuk

    2014-05-01

    Full Text Available Insulin resistance (IR is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion.IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell. Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades.This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.

  11. Effect of insulin on the inflammatory and acute phase response after burn injury.

    Science.gov (United States)

    Jeschke, Marc G; Boehning, Darren F; Finnerty, Celeste C; Herndon, David N

    2007-09-01

    After a severe burn, the liver plays a pivotal role by modulating inflammatory processes, metabolic pathways, immune functions, and the acute phase response. Therefore, liver integrity and function are important for recovery. A thermal injury, however, causes hepatic damage by inducing hepatic edema, fatty infiltration, hepatocyte apoptosis, and metabolic derangements associated with insulin resistance and impaired insulin signaling. In preliminary studies, we found that these pathophysiological processes are related to hepatic inflammation, altered intracellular signaling, and mitochondrial dysfunction. We hypothesize that modulation of these processes with insulin could improve hepatic structure and function and, therefore, outcome of burned and critically ill patients. Insulin administration improves survival and decreases the rate of infections in severely burned and critically ill patients. Here, we show that insulin administration decreases the synthesis of proinflammatory cytokines and signal transcription factors and improves hepatic structure and function after a severe burn injury; insulin also restores hepatic homeostasis and improves hepatic dysfunction postburn via alterations in the signaling cascade.

  12. Insulin resistance alters islet morphology in nondiabetic humans

    DEFF Research Database (Denmark)

    Mezza, Teresa; Muscogiuri, Giovanna; Sorice, Gian Pio;

    2014-01-01

    Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects...... pancreatic β-cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared...... insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of β- and α-cells that resulted in an altered β-cell-to-α-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from...

  13. Excess exposure to insulin is the primary cause of insulin resistance and its associated atherosclerosis.

    Science.gov (United States)

    Cao, Wenhong; Ning, Jie; Yang, Xuefeng; Liu, Zhenqi

    2011-11-01

    The main goal of this review is to provide more specific and effective targets for prevention and treatment of insulin resistance and associated atherosclerosis. Modern technologies and medicine have vastly improved human health and prolonged the average life span of humans primarily by eliminating various premature deaths and infectious diseases. The modern technologies have also provided us abundant food and convenient transportation tools such as cars. As a result, more people are becoming overfed and sedentary. People are generally ingesting more calories than their bodies' need, leading to the so-called "positive energy imbalance", which is inseparable from the development of insulin resistance and its associated atherosclerosis. A direct consequence of insulin resistance is hyperinsulinemia. The current general view is that insulin is not functional properly in the presence of insulin resistance. Thus, the role of insulin itself in the development of insulin resistance and associated atherosclerosis has not been recognized. We have recently observed that the basal level of insulin signaling is increased in the presence of insulin resistance and hyperinsulinemia. In this review, we will explain how the increased basal insulin signaling contributes to the development of insulin resistance and associated atherosclerosis. We will first explain how insulin causes insulin resistance through two arbitrary stages (before and after the presence of obvious insulin resistance), and, then, explain how the excess exposure to insulin and the relative insulin insufficiency contributes to the atherosclerotic diseases. We propose that blockade of the excess insulin signaling is a viable approach to prevent and/or reverse insulin resistance and its associated atherosclerosis.

  14. Insulin resistance and laminitis in horses

    OpenAIRE

    Horn, Isabella

    2009-01-01

    Kliinisen hevos- ja pienelÀinlÀÀketieteen laitos, sisÀtautiopin oppiaine. Laminitis is a common painful condition in horses that often has a poor outcome. The aetiology of laminitis has been widely studied, but still not completely understood. There is some evidence that pasture associated laminitis is one of the most common forms of laminitis , and this is most likely associated with underlying endocrine dysfunction i.e. insulin resistance. However, what the prevalence of insulin resi...

  15. A new antihypertensive drug ameliorates insulin resistance

    Institute of Scientific and Technical Information of China (English)

    Yan-xia LIU

    2012-01-01

    Insulin resistance (IR)is defined as decreased sensitivity and/or responsiveness to insulin that promote glucose disposal.A growing body of clinical and epidemiologic evidence indicates that essential hypertension and IR often coexist[1].Approximately 50 percent of patients with hypertension can be considered to have IR and hyperinsulinemia[1].This inextricable linkage between hypertension and IR has been identified to increase the prevalence of cardiovascular disease (CVD)and new onset of type Ⅱ diabetes that is the major cause of morbidity and mortality in this clinical syndrome[2].However,the driving force linking IR and hypertension remains to be fully elucidated.

  16. Relationship between adiponectin, obesity and insulin resistance

    Directory of Open Access Journals (Sweden)

    Guilherme Ardenghi Balsan

    2015-02-01

    Full Text Available Objectives: the conditions of obesity and overweight pose a major risk for a number of comorbidities, including clinical syndromes resulting from atherosclerotic disease. Recent studies strongly indicate that adipose tissue is an active endocrine organ that secretes bioactive factors such as adipokines. Adiponectin appears to have a regulatory role in the mechanism of insulin resistance and in the development of atherosclerosis. This systematic review aims to evaluate the anti-atherogenic effects of adiponectin and its properties to improve and mimic metabolic and vascular actions of insulin and its influence on endothelial function. Methods: a qualitative, exploratory and literature review was performed in the PubMed, Portal Capes and Scielo databases using as key-words "adiponectin", "obesity", "insulin resistance", "anti-inflammatory", "therapeutic strategies" and "future prospects". Results: evidence suggests that adiponectin has anti-atherogenic properties with anti-inflammatory effects on the vascular wall. Moreover, it modifies the vascular intracellular signaling and has indirect antioxidant effects on the human myocardium. On the other hand, there are studies suggesting that increased levels of adiponectin are paradoxically associated with a worse prognosis in heart failure syndrome, although the mechanisms are not clear. Conclusion: it is not clear whether adiponectin levels have any clinical significance for risk stratification in cardiovascular disease or if they simply reflect the activation of complex underlying mechanisms. Changes in lifestyle and some drug treatments for hypertension and coronary heart disease have shown significant effect to increase adiponectin levels, and simultaneously decrease in insulin resistance and endothelial dysfunction.

  17. Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population

    Directory of Open Access Journals (Sweden)

    Sudha S. Shankar, MD

    2015-12-01

    Conclusions: Significant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712.

  18. Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study

    NARCIS (Netherlands)

    A.E. Hak (Liesbeth); H.A.P. Pols (Huib); C.D. Stehouwer (Coen); J. Meijer (John); A.J. Kiliaan (Amanda); M.M.B. Breteler (Monique); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2001-01-01

    textabstractInsulin resistance, which is highly prevalent in the elderly, is suggested to be accompanied by an increased acute phase response. Until now, it is unclear whether cellular adhesion molecules are involved in the clustering of insulin resistance. In the present study, we

  19. Defective insulin response of cyclic adenosine monophosphate-dependent protein kinase in insulin-resistant humans.

    OpenAIRE

    Kida, Y; Nyomba, B L; Bogardus, C; Mott, D M

    1991-01-01

    Insulin-stimulated glycogen synthase activity in human muscle correlates with insulin-mediated glucose disposal and is reduced in insulin-resistant subjects. Inhibition of the cyclic AMP-dependent protein kinase (A-kinase) is considered as a possible mechanism of insulin action for glycogen synthase activation. In this study, we investigated the time course of insulin action on human muscle A-kinase activity during a 2-h insulin infusion in 13 insulin-sensitive (group S) and 7 insulin-resista...

  20. Methodological and Clinical Studies on Insulin Resistance in Childhood

    OpenAIRE

    Rössner, Sophia

    2011-01-01

    Insulin resistance is a condition in which adequate amounts of insulin fail to give an adequate response in target tissues. This thesis is based on five different studies, aiming to investigate different aspects of insulin resistance and the assessment methods thereof in children and in adults. The rationale for performing these studies is that insulin resistance is a key component of the metabolic syndrome and crucial in the development of type 2 diabetes. Concomitant with the in...

  1. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

    DEFF Research Database (Denmark)

    Højlund, Kurt

    2014-01-01

    . These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance...

  2. Vascular Stiffness in Insulin Resistance and Obesity

    Directory of Open Access Journals (Sweden)

    Guanghong eJia

    2015-08-01

    Full Text Available Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis and stiffness, with attendant increased risk of cardiovascular and chronic kidney disease. Although the underlying mechanisms and mediators of vascular stiffness are not well understood, accumulating evidence supports the role of metabolic and immune dysregulation related to increased adiposity, activation of the renin angiotensin aldosterone system, reduced bioavailable nitric oxide, increased vascular extracellular matrix (ECM and ECM remodeling in the pathogenesis of vascular stiffness. This review will give a brief overview of the relationship between obesity, insulin resistance and increased vascular stiffness to provide a contemporary understanding of the proposed underlying mechanisms and potential therapeutic strategies.

  3. Mitochondrial Deficiency Is Associated With Insulin Resistance

    OpenAIRE

    Goodpaster, Bret H.

    2013-01-01

    The specific cellular underpinnings or mechanisms of insulin resistance (IR) are not clear. Here I present evidence to support a causal association between mitochondrial energetics and IR. A large body of literature indicates that mitochondrial capacity for oxidative metabolism is lower in human obesity and type 2 diabetes. Whether or not mitochondria play a causal role in IR is hotly debated. First, IR can be caused by many factors, many of which may or may not involve mitochondria. These in...

  4. Acute and chronic effects of glyceryl trinitrate therapy on insulin and glucose regulation in humans.

    Science.gov (United States)

    Jedrzkiewicz, Sean; Parker, John D

    2013-05-01

    This study examined the effect of acute and sustained transdermal glyceryl trinitrate (GTN) therapy on insulin and glucose regulation. Totally, 12 males (18-30 years) underwent a glucose tolerance test at baseline (visit 1), 90 minutes after acute transdermal GTN 0.6 mg/h (visit 2), following 7 days of continuous GTN (visit 3), and 2 to 3 days after stopping GTN (visit 4). At each visit, plasma glucose and insulin concentrations were measured before and 30, 60, 90, and 120 minutes after a 75-g oral glucose load. Indices of glucose metabolism that were examined included the insulin sensitivity index, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulinogenic index. The acute administration of GTN had no effect on glucose and insulin responses (visit 2). However, after 7 days of GTN exposure (visit 3) there was an increase in the mean glucose concentration measured after the oral glucose load. On visit 1, the mean glucose concentration (± standard deviation) following the 75 g oral glucose challenge was 5.7 ± 0.5 µmol/L. On visit 3, after 7 days of transdermal GTN therapy, the mean glucose concentration after the oral glucose was significantly higher; 6.2 ± 0.5 µmol/L (P GTN therapy modifies glucose metabolism causing evidence of increased insulin resistance during sustained therapy in normal humans.

  5. Adrenocortical tumors and insulin resistance: What is the first step?

    Science.gov (United States)

    Altieri, Barbara; Tirabassi, Giacomo; Casa, Silvia Della; Ronchi, Cristina L; Balercia, Giancarlo; Orio, Francesco; Pontecorvi, Alfredo; Colao, Annamaria; Muscogiuri, Giovanna

    2016-06-15

    The pathogenetic mechanisms underlying the onset of adrenocortical tumors (ACTs) are still largely unknown. Recently, more attention has been paid to the role of insulin and insulin-like growth factor (IGF) system on general tumor development and progression. Increased levels of insulin, IGF-1 and IGF-2 are associated with tumor cell growth and increased risk of cancer promotion and progression in patients with type 2 diabetes. Insulin resistance and compensatory hyperinsulinemia may play a role in adrenal tumor growth through the activation of insulin and IGF-1 receptors. Interestingly, apparently non-functioning ACTs are often associated with a high prevalence of insulin resistance and metabolic syndrome. However, it is unclear if ACT develops from a primary insulin resistance and compensatory hyperinsulinemia or if insulin resistance is only secondary to the slight cortisol hypersecretion by ACT. The aim of this review is to summarize the current evidence regarding the relationship between hyperinsulinemia and adrenocortical tumors. PMID:26637955

  6. Adrenocortical tumors and insulin resistance: What is the first step?

    Science.gov (United States)

    Altieri, Barbara; Tirabassi, Giacomo; Della Casa, Silvia; Ronchi, Cristina L; Balercia, Giancarlo; Orio, Francesco; Pontecorvi, Alfredo; Colao, Annamaria; Muscogiuri, Giovanna

    2016-06-15

    The pathogenetic mechanisms underlying the onset of adrenocortical tumors (ACTs) are still largely unknown. Recently, more attention has been paid to the role of insulin and insulin-like growth factor (IGF) system on general tumor development and progression. Increased levels of insulin, IGF-1 and IGF-2 are associated with tumor cell growth and increased risk of cancer promotion and progression in patients with type 2 diabetes. Insulin resistance and compensatory hyperinsulinemia may play a role in adrenal tumor growth through the activation of insulin and IGF-1 receptors. Interestingly, apparently non-functioning ACTs are often associated with a high prevalence of insulin resistance and metabolic syndrome. However, it is unclear if ACT develops from a primary insulin resistance and compensatory hyperinsulinemia or if insulin resistance is only secondary to the slight cortisol hypersecretion by ACT. The aim of this review is to summarize the current evidence regarding the relationship between hyperinsulinemia and adrenocortical tumors.

  7. Insulin signaling and glucose transport in insulin resistant human skeletal muscle

    OpenAIRE

    Karlsson, Håkan KR

    2005-01-01

    Insulin resistance in skeletal muscle is a hallmark feature of Type 2 diabetes mellitus. The overall aim of this thesis was to investigate downstream intermediates in the insulin signaling pathway in an attempt to characterize the molecular mechanism of skeletal muscle insulin resistance in Type 2 diabetes. Skeletal muscle biopsies were obtained from healthy and Type 2 diabetic subjects before and after an in vivo hyperinsulinemic infusion. Insulin infusion increased the...

  8. Fructose, insulin resistance, and metabolic dyslipidemia

    Directory of Open Access Journals (Sweden)

    Adeli Khosrow

    2005-02-01

    Full Text Available Abstract Obesity and type 2 diabetes are occurring at epidemic rates in the United States and many parts of the world. The "obesity epidemic" appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in the amount of dietary fructose consumption from high intake of sucrose and high fructose corn syrup, a common sweetener used in the food industry. A high flux of fructose to the liver, the main organ capable of metabolizing this simple carbohydrate, perturbs glucose metabolism and glucose uptake pathways, and leads to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG synthesis, driven by the high flux of glycerol and acyl portions of TG molecules from fructose catabolism. These metabolic disturbances appear to underlie the induction of insulin resistance commonly observed with high fructose feeding in both humans and animal models. Fructose-induced insulin resistant states are commonly characterized by a profound metabolic dyslipidemia, which appears to result from hepatic and intestinal overproduction of atherogenic lipoprotein particles. Thus, emerging evidence from recent epidemiological and biochemical studies clearly suggests that the high dietary intake of fructose has rapidly become an important causative factor in the development of the metabolic syndrome. There is an urgent need for increased public awareness of the risks associated with high fructose consumption and greater efforts should be made to curb the supplementation of packaged foods with high fructose additives. The present review will discuss the trends in fructose consumption, the metabolic consequences of increased fructose intake, and the molecular mechanisms leading to fructose-induced lipogenesis, insulin resistance and metabolic dyslipidemia.

  9. Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance.

    Science.gov (United States)

    Mohamad, Mashani; Mitchell, Sarah Jayne; Wu, Lindsay Edward; White, Melanie Yvonne; Cordwell, Stuart James; Mach, John; Solon-Biet, Samantha Marie; Boyer, Dawn; Nines, Dawn; Das, Abhirup; Catherine Li, Shi-Yun; Warren, Alessandra; Hilmer, Sarah Nicole; Fraser, Robin; Sinclair, David Andrew; Simpson, Stephen James; de Cabo, Rafael; Le Couteur, David George; Cogger, Victoria Carroll

    2016-08-01

    While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' are essential for insulin transfer across the liver sinusoidal endothelium and that age-related loss of fenestrations causes an impaired insulin clearance and hyperinsulinemia, induces hepatic insulin resistance, impairs hepatic insulin signaling, and deranges glucose homeostasis. To further define the role of fenestrations in hepatic insulin signaling without any of the long-term adaptive responses that occur with aging, we induced acute defenestration using poloxamer 407 (P407), and this replicated many of the age-related changes in hepatic glucose and insulin handling. Loss of fenestrations in the liver sinusoidal endothelium is a hallmark of aging that has previously been shown to cause deficits in hepatic drug and lipoprotein metabolism and now insulin. Liver defenestration thus provides a new mechanism that potentially contributes to age-related insulin resistance. PMID:27095270

  10. Serum Insulin, Proinsulin and Proinsulin/Insulin Ratio in Type 2 Diabetic Patients: As an Index of β-Cell Function or Insulin Resistance

    OpenAIRE

    Kim, Nan Hee; Kim, Dong Lim; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop

    2000-01-01

    Background Although insulin resistance and decreased insulin secretion are characteristics of established type 2 DM, which of these metabolic abnormalities is the primary determinant of type 2 DM is controversial. It is also not well known how insulin resistance and beta cell dysfunction influence serum insulin, proinsulin, proinsulin/insulin ratio in type 2 DM. Methods We compared serum insulin, proinsulin and proinsulin/insulin ratio in type 2 diabetic patients and control subjects. We also...

  11. A paradox: Insulin inhibits expression and secretion of resistin which induces insulin resistance

    Institute of Scientific and Technical Information of China (English)

    Feng Liu; Mei Guo; Rong-Hua Chen; Xi-Rong Guo; Hong-Qi Fan; Jie Qiu; Bin Wang; Min Zhang; Nan Gu; Chun-Mei Zhang; Li Fei; Xiao-Qing Pan

    2008-01-01

    AIM:To confirm whether insulin regulates resistin expression and secretion during differentiation of 3T3-L1 preadipocytes and the relationship of resistin with insulin resistance both in vivo and in vitro. METHODS: Supernatant resistin was measured during differentiation of 3T3-L1 preadipocytes. L6 rat myoblasts and hepatoma cell line H4IIE were used to confirm the cellular function of resistin. Diet-induced obese rats were used as an insulin resistance model to study the relationship of resistin with insulin resistance.RESULTS: Resistin expression and secretion were enhanced during differentiation 3T3-L1 preadipocytes. This cellular differentiation stimulated resistin expression and secretion, but was suppressed by insulin. Resistin also induced insulin resistance in H4IIE hepatocytes and L6 myoblasts. In diet-induced obese rats, serum resistin levels were negatively correlated with insulin sensitivity,but not with serum insulin. CONCLUSION: Insulin can inhibit resistin expression and secretion in vitro, but insulin is not a major regulator of resistin in vivo. Fat tissue mass affects insulin sensitivity by altering the expression and secretion of resistin.

  12. Metabolic syndrome and insulin resistance in obese adolescents

    Directory of Open Access Journals (Sweden)

    Amanda Oliva Gobato

    2014-03-01

    Full Text Available Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI, body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032 and with metabolic syndrome (p=0.006. All body composition indicators were correlated with insulin resistance (p<0.01. In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.

  13. Less of insulin desensitization in sympathetic nerve terminals from wistar rats with insulin resistance.

    Science.gov (United States)

    Chi, T C; Liu, I M; Cheng, J T

    2000-04-12

    In an attempt to determine the effect of hyperinsulinemia on sympathetic function, release of norepinephrine (NE) from isolated aorta by insulin was measured in Wistar rats with insulin resistance. Insulin resistance was produced when the hypoglycemic action of glibenclamide at a dose of 10 mg/kg was almost abolished in rats that received daily injections of long-acting insulin for 15 days. Moreover, the stimulatory effect of insulin on glucose uptake was markedly reduced in both skeletal muscle strips and white adipocytes obtained from these rats with insulin resistance. However, the stimulatory effects of insulin at concentrations from 5 to 15 U/l on the release of NE from the aortic strip of insulin-resistant rats were not modified in the same manner but only slightly reduced compared with that of normal rats. These results suggest that insulin desensitization was produced later in sympathetic nerve terminals than in other organs in insulin-resistant rats and this may be helpful to explain the sympathetic hyperactivity associated with diabetes in clinics.

  14. Method for preventing and/or treating insulin resistance

    NARCIS (Netherlands)

    Nieuwdorp, M.; Vos, de W.M.

    2013-01-01

    The present invention describes use of Eubacterium hallii et rel. and/or Alcaligenes faecalis et rel., as well as pharmaceutical, food, or feed compositions comprising these bacteria, as a medicament, in particular for preventing and/or treating insulin resistance and/or insulin resistance-related c

  15. Insulin resistance : pathophysiology in South Asians & therapeutic strategies

    NARCIS (Netherlands)

    Sleddering, Maria Alexandra

    2014-01-01

    This thesis describes the pathophysiology of insulin resistance in the South Asian population and comprises studies on pharmacological and weight loss interventions in insulin resistant patients. Because of the increasing number of patients with obesity and T2DM, more research is needed to identify

  16. Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization

    Science.gov (United States)

    Sears, D. D.; Hsiao, G.; Hsiao, A.; Yu, J. G.; Courtney, C. H.; Ofrecio, J. M.; Chapman, J.; Subramaniam, S.

    2009-01-01

    Cellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPARγ ligands. We characterized 72 human subjects by relating their clinical phenotypes with functional pathway alterations. We transcriptionally profiled 364 biopsies harvested before and after hyperinsulinemic-euglycemic clamp studies, at baseline and after 3-month TZD treatment. We have identified molecular and functional characteristics of insulin resistant subjects and distinctions between TZD treatment responder and nonresponder subjects. Insulin resistant subjects exhibited alterations in skeletal muscle (e.g., glycolytic flux and intramuscular adipocytes) and adipose tissue (e.g., mitochondrial metabolism and inflammation) that improved relative to TZD-induced insulin sensitization. Pre-TZD treatment expression of MLXIP in muscle and HLA-DRB1 in adipose tissue from insulin resistant subjects was linearly predictive of post-TZD insulin sensitization. We have uniquely characterized coordinated cellular and tissue functional pathways that are characteristic of insulin resistance, TZD-induced insulin sensitization, and potential TZD responsiveness. PMID:19841271

  17. Insulin resistance is associated with reduced fasting and insulin-stimulated glycogen synthase phosphatase activity in human skeletal muscle.

    OpenAIRE

    Kida, Y; Esposito-Del Puente, A; Bogardus, C; Mott, D M

    1990-01-01

    Insulin-stimulated glycogen synthase activity in human skeletal muscle correlates with insulin-mediated glucose disposal rate (M) and is reduced in insulin-resistant subjects. We have previously reported reduced insulin-stimulated glycogen synthase activity associated with reduced fasting glycogen synthase phosphatase activity in skeletal muscle of insulin-resistant Pima Indians. In this study we investigated the time course for insulin stimulation of glycogen synthase and synthase phosphatas...

  18. Insulin resistance in human subjects having impaired glucose regulation

    International Nuclear Information System (INIS)

    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)

  19. Whole-body and hepatic insulin resistance in obese children.

    Directory of Open Access Journals (Sweden)

    Lorena del Rocío Ibarra-Reynoso

    Full Text Available Insulin resistance may be assessed as whole body or hepatic.To study factors associated with both types of insulin resistance.Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (<6.67 ng/ml. We determined metabolite and hormone levels and performed a liver ultrasound.The majority, 73.1%, of obese children had whole-body insulin resistance and hepatic insulin resistance, while 7% did not have either type. HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother's BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver.In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance.

  20. The Effect of Different Intensities of Acute Aerobic Exercise on Plasma Resistin Concentration and Insulin Resistance Index in Type 2 Diabetic Males

    Directory of Open Access Journals (Sweden)

    Ziba Davoudi

    2016-04-01

    Conclusion: It can be stated that acute exercise with different intensities does not affect resistin action in individuals with diabetes. These results may be due to the constant energy cost which is equivalent to 300 kcal per session, having no influence on the study variables.

  1. Relationship between insulin resistance and plasma endothelin in hypertension patients

    International Nuclear Information System (INIS)

    To explore the relationship between plasma endothelin and hypertension insulin resistance, and the improvement of insulin resistance in hypertension patients treated with captopril and l-amlodipine, 25 patients with primary hypertension and impaired glucose tolerance were selected and treated by captopril and l-amlodipine. Systolic pressure, diastolic pressure, fasting blood glucose, insulin and insulin antibody were measured before and after treatment and compared with healthy controls. The results showed that the plasma ET-1 level in hypertension group was significantly higher than that of healthy controls (P<0.01), and he plasma ET-1 level was positively correlated with FPG, FINS, Anti-INS, HOMA-IR. The systolic pressure, diastolic pressure, fasting blood glucose, insulin, insulin antibody and insulin resistance index in hypertension patients were decreased significantly after treatment (P<0.05). There is a good correlation between endothelin and insulin resistance index in hypertension patients. Captopril and l-amlodipine had obvious improvement effect on insulin resistance in hypertension patients. (authors)

  2. Insulin resistance and breast-cancer risk.

    Science.gov (United States)

    Bruning, P F; Bonfrèr, J M; van Noord, P A; Hart, A A; de Jong-Bakker, M; Nooijen, W J

    1992-10-21

    Life-style has a major influence on the incidence of breast cancer. To evaluate the effects of life-style related metabolic-endocrine factors on breast cancer risk we conducted a case-control study comparing 223 women aged 38 to 75 years presenting with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer, who participated in a population-based breast cancer screening program. Women reporting diabetes mellitus were excluded. Sera from 110 women of the same age group presenting with early stage melanoma, lymphoma or cervical cancer were used as a second 'other-cancer control group'. Serum levels of C-peptide were significantly higher in early breast cancer cases compared to controls. The same was found for the ratios C-peptide to glucose or C-peptide to fructosamine, indicating insulin resistance. Sex hormone binding globulin was inversely, triglycerides and available estradiol were positively related to C-peptide. Serum C-peptide levels were related to body mass index (BMI), and to waist/hip ratio (WHR), in particular in controls. However, the relative increase of C-peptide, C-peptide to glucose or C-peptide to fructosamine in cases was independent of BMI or WHR. The log relative risk was linearly related to the log C-peptide levels. Relative risk according to quintiles, and adjusted for age, family history, BMI and WHR, for women at the 80% level was 2.9 as compared with those at the 20% level for C-peptide. Elevated C-peptide or C-peptide to fructosamine values were not observed in the sera from women belonging to the 'other-cancer control group'. This study suggests that hyperinsulinemia with insulin resistance is a significant risk factor for breast cancer independent of general adiposity or body fat distribution. PMID:1399128

  3. Related Factors of Insulin Resistance in Korean Children: Adiposity and Maternal Insulin Resistance

    OpenAIRE

    Kang-Sook Lee; Yang-Im Hur; Jihyun Song; Young-Gyu Cho; Jae-Heon Kang

    2011-01-01

    Increased adiposity and unhealthy lifestyle augment the risk for type 2 diabetes in children with familial predisposition. Insulin resistance (IR) is an excellent clinical marker for identifying children at high risk for type 2 diabetes. This study was conducted to investigate parental, physiological, behavioral and socio-economic factors related to IR in Korean children. This study is a cross-sectional study using data from 111 children aged 7 years and their parents. Homeostasis model asses...

  4. Prevalence of insulin resistance in obese adolescents

    Directory of Open Access Journals (Sweden)

    Aman B. Pulungan

    2013-01-01

    Full Text Available Background Childhood obesity is a global health problem, with the prevalence is differed in each country and affected by many factors, such as lifestyle and physical activity. Insulin resistance (IR as a basic mechanism of several metabolic diseases in obesity, is related with metabolic syndrome (MetS along with its long term complications, such as type 2 diabetes mellitus (T2DM. Several factors are known to be associated with IR, and the presence of acanthosis nigricans (AN has an important meaning in predicting IR.Objectives To assess the prevalence of IR, MetS in obese adolescents and its potentially associated factors, such as gender, signs of AN, and family history of metabolic diseases.Methods A cross-sectional study was performed in obese adolescents, aged 12-15 years, over a two-month period. Fasting blood glucose, insulin, and lipid profiles were measured. Oobesity was defined using body mass index (BMI. Insulin resistance was quantified by the homeostasis model assessment for IR (HOMA-IR. Metabolic syndrome was defined according to the International Diabetes Federation (IDF 2007 criteria.Results Of 92 obese adolescents, IR was found in 38% of subjects, with females predominating (57.2%. Signs of AN were seen in 71.4% of subjects and a positive family history of metabolic diseases was found in 82.8% of subjects, including family history of obesity, type 2 diabetes mellitus (T2DM, and hypertension. Less than 10% of subjects were considered to be in a prediabetic state, and none had T2DM. No statistical significance was found between gender, family history, or signs of AN and IR (P>0.05. Metabolic syndromes was found in 19.6% of subjects, with the following prevalences for each component: 34.8% for hypertension, 78.3% for central obesity, 8.7% for impaired fasting glucose (IFG, 22.8% for low levels of HDL, and 21.7% for high triglyceride levels. A strong correlation was found between IR and IFG with OR=5.69 (95%CI 1.079 – 29.993, P=0

  5. Prevalence of insulin resistance in obese adolescents

    Directory of Open Access Journals (Sweden)

    Aman B. Pulungan

    2013-05-01

    Full Text Available Background Childhood obesity is a global health problem, with the prevalence is differed in each country and affected by many factors, such as lifestyle and physical activity. Insulin resistance (IR as a basic mechanism of several metabolic diseases in obesity, is related with metabolic syndrome (MetS along with its long term complications, such as type 2 diabetes mellitus (T2DM. Several factors are known to be associated with IR, and the presence of acanthosis nigricans (AN has an important meaning in predicting IR. Objectives To assess the prevalence of IR, MetS in obese adolescents and its potentially associated factors, such as gender, signs of AN, and family history of metabolic diseases. Methods A cross-sectional study was performed in obese adolescents, aged 12-15 years, over a two-month period. Fasting blood glucose, insulin, and lipid profiles were measured. Oobesity was defined using body mass index (BMI. Insulin resistance was quantified by the homeostasis model assessment for IR (HOMA-IR. Metabolic syndrome was defined according to the International Diabetes Federation (IDF 2007 criteria. Results Of 92 obese adolescents, IR was found in 38% of subjects, with females predominating (57.2%. Signs of AN were seen in 71.4% of subjects and a positive family history of metabolic diseases was found in 82.8% of subjects, including family history of obesity, type 2 diabetes mellitus (T2DM, and hypertension. Less than 10% of subjects were considered to be in a prediabetic state, and none had T2DM. No statistical significance was found between gender, family history, or signs of AN and IR (P>0.05. Metabolic syndromes was found in 19.6% of subjects, with the following prevalences for each component: 34.8% for hypertension, 78.3% for central obesity, 8.7% for impaired fasting glucose (IFG, 22.8% for low levels of HDL, and 21.7% for high triglyceride levels. A strong correlation was found between IR and IFG with OR=5.69 (95%CI 1.079 – 29.993, P=0

  6. Insulin resistance and mitochondrial function in skeletal muscle

    DEFF Research Database (Denmark)

    Dela, Flemming; Helge, Jørn Wulff

    2013-01-01

    are used in the attempt to resolve the mechanisms of insulin resistance. In this context, a dysfunction of mitochondria in the skeletal muscle has been suggested to play a pivotal role. It has been postulated that a decrease in the content of mitochondria in the skeletal muscle can explain the insulin...... resistance. Complementary to this also specific defects of components in the respiratory chain in the mitochondria have been suggested to play a role in insulin resistance. A key element in these mechanistic suggestions is inability to handle substrate fluxes and subsequently an accumulation of ectopic...... intramyocellular lipids, interfering with insulin signaling. In this review we will present the prevailing view-points and argue for the unlikelihood of this scenario being instrumental in human insulin resistance. This article is part of a Directed Issue entitled: Bioenergetic dysfunction....

  7. Acute and chronic effects of glyceryl trinitrate therapy on insulin and glucose regulation in humans.

    Science.gov (United States)

    Jedrzkiewicz, Sean; Parker, John D

    2013-05-01

    This study examined the effect of acute and sustained transdermal glyceryl trinitrate (GTN) therapy on insulin and glucose regulation. Totally, 12 males (18-30 years) underwent a glucose tolerance test at baseline (visit 1), 90 minutes after acute transdermal GTN 0.6 mg/h (visit 2), following 7 days of continuous GTN (visit 3), and 2 to 3 days after stopping GTN (visit 4). At each visit, plasma glucose and insulin concentrations were measured before and 30, 60, 90, and 120 minutes after a 75-g oral glucose load. Indices of glucose metabolism that were examined included the insulin sensitivity index, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulinogenic index. The acute administration of GTN had no effect on glucose and insulin responses (visit 2). However, after 7 days of GTN exposure (visit 3) there was an increase in the mean glucose concentration measured after the oral glucose load. On visit 1, the mean glucose concentration (± standard deviation) following the 75 g oral glucose challenge was 5.7 ± 0.5 µmol/L. On visit 3, after 7 days of transdermal GTN therapy, the mean glucose concentration after the oral glucose was significantly higher; 6.2 ± 0.5 µmol/L (P versus 6.9 (6.8) on visit 3 (P < .015). Other indices of glucose metabolism did not change. These observations document that GTN therapy modifies glucose metabolism causing evidence of increased insulin resistance during sustained therapy in normal humans. PMID:23230283

  8. The Effect of Acute Exercise on Serum Vaspin Level and Its Relation to Insulin Sensitivity in Overweight Elderly Men

    Directory of Open Access Journals (Sweden)

    Jabbar Bashiri

    2014-08-01

    Full Text Available Background: Vaspin is a new discovered adipocytokine which is a member of serine protease inhibitor family secreted from adipose tissue and might play a role in insulin sensitivity. The purpose of this study was to investigate the effect of acute exercise on serum vaspin levels and its relation to insulin sensitivity in overweight elderly men. Materials and Methods: In this semi-experimental study, 12 healthy elderly men volunteers randomly selected and performed one session aerobic exercise including 30 minutes of cycling at 70-75% of HRmax, which was followed by 30 minutes of recovery. Three blood samples were taken before exercise, immediately after exercise and after 30 minutes of recovery. Data were analyzed by repeated measure ANOVA and Bonferroni test and Pearson’s correlations were performed to identify possible relationship among the assessed variables. Statistical significance was set at p≤0.05. Results: There were no significant differences for vaspin across time. Insulin and glucose concentration and insulin resistance decreased immediately after exercise. However insulin concentration and insulin resistance returned to pre-exercise level at the end of recovery. Furthermore, no significant correlations were observed among the variables assessed except for the expected between insulin level and insulin resistance. Conclusion: These results indicate that a sub-maximal aerobic workout does not result in significant changes in vaspin levels in elderly men. Furthermore, we observed that vaspin is not associated with insulin sensitivity in this study.

  9. The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

    OpenAIRE

    Lewitt, Moira S; Dent, Mairi S.; Kerstin Hall

    2014-01-01

    The insulin-like growth factor (IGF) system, acting in concert with other hormone axes, is important in normal metabolism. In obesity, the hyperinsulinaemia that accompanies peripheral insulin resistance leads to reduced growth hormone (GH) secretion, while total IGF-I levels are relatively unchanged due to increased hepatic GH sensitivity. IGF-binding protein (IGFBP)-1 levels are suppressed in relation to the increase in insulin levels in obesity and low levels predict the development of typ...

  10. Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis

    OpenAIRE

    Semple, Robert K.; Sleigh, Alison; Murgatroyd, Peter R; Adams, Claire A.; Bluck, Les; Jackson, Sarah; Vottero, Alessandra; Kanabar, Dipak; Charlton-Menys, Valentine; Durrington, Paul; Soos, Maria A.; Carpenter, T. Adrian; David J Lomas; Cochran, Elaine K.; Gorden, Phillip

    2009-01-01

    Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fat...

  11. Experimental study of the hexosamine biosynthesis pathway and insulin resistance

    Institute of Scientific and Technical Information of China (English)

    FeiYE; JiangLI; Jin-ying; TIAN

    2004-01-01

    AIM: To set up the GDH method and the insulin resistance cell model for screening the glutamine:fructose-6-phosphate amidotransferase (GFAT) inhibitors. METHODS: Glutamine can be converted to glutamate by GFAT, then, affected with APAD to produce APADH by GDH. APADH showed a peak at the 360 nm wavelength. Each factor of the active system was regulated. After the insulin administration in HIRc cells, the GFAT activity and the insulin-induced glucose uptake were

  12. The Association Between IGF-I and Insulin Resistance

    DEFF Research Database (Denmark)

    Friedrich, Nele; Thuesen, Betina; Jørgensen, Torben;

    2012-01-01

    the association between IGF-I level and insulin resistance in a Danish general population.RESEARCH DESIGN AND METHODSIncluded were 3,354 adults, aged 19-72 years, from the cross-sectional Health2006 study. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to estimate insulin...... with intermediate (Q3) IGF-I levels. These associations remained statistically significant after the exclusion of subjects with type 2 diabetes and by using the updated computer HOMA2-IR model.CONCLUSIONSLow- and high-normal IGF-I levels are both related to insulin resistance. The biological mechanism......OBJECTIVEIGF-I has an almost 50% amino acid sequence homology with insulin and elicits nearly the same hypoglycemic response. Studies showed that low and high IGF-I levels are related to impaired glucose tolerance and to a higher risk of type 2 diabetes. The aim of the current study was to evaluate...

  13. Treatment of Type B Insulin Resistance: A Novel Approach to Reduce Insulin Receptor Autoantibodies

    OpenAIRE

    "R. Malek; Chong, A. Y.; Lupsa, B. C.; Lungu, A. O.; Cochran, E. K.; Soos, M. A.; Semple, R.K.; Balow, J E; Gorden, P

    2010-01-01

    Background: Type B insulin resistance belongs to a class of diseases caused by an autoantibody to a cell surface receptor. Blockade of insulin action results in hyperglycemia, hypercatabolism, severe acanthosis nigricans, and hyperandrogenism in women. This rare autoimmune disorder has been treated with various forms of immunosuppression with mixed success.

  14. Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization

    OpenAIRE

    Sears, D. D.; Hsiao, G.; Hsiao, A.; Yu, J. G.; Courtney, C. H.; J.M. Ofrecio; Chapman, J; Subramaniam, S

    2009-01-01

    Cellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPARγ ligands. We characterized 72 human subjects by relating their clinical phenotypes with functional pathway alterations. We transcriptionally profiled 364 biopsies harvested before and after hyperinsulinemic-euglycemic clamp studies, at baseline and after 3-month TZD treatment. We have identified molecula...

  15. Related Factors of Insulin Resistance in Korean Children: Adiposity and Maternal Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Kang-Sook Lee

    2011-12-01

    Full Text Available Increased adiposity and unhealthy lifestyle augment the risk for type 2 diabetes in children with familial predisposition. Insulin resistance (IR is an excellent clinical marker for identifying children at high risk for type 2 diabetes. This study was conducted to investigate parental, physiological, behavioral and socio-economic factors related to IR in Korean children. This study is a cross-sectional study using data from 111 children aged 7 years and their parents. Homeostasis model assessment of insulin resistance (HOMA-IR was calculated using fasting glucose and insulin level as a marker of IR. All children’s adiposity indices (r = 0.309–0.318, all P-value = 0.001 and maternal levels of fasting insulin (r = 0.285, P-value = 0.003 and HOMA-IR (r = 0.290, P-value = 0.002 were positively correlated with children’s HOMA-IR level. There was no statistical difference of children’s HOMA-IR level according to children’s lifestyle habits and socioeconomic status of families. An increase of 1 percentage point in body fat was related to 2.7% increase in children’s HOMA-IR (P-value < 0.001 and an increase of 1% of maternal level of HOMA-IR was related to 0.2% increase in children’s HOMA-IR (P-value = 0.002. This study shows that children’s adiposity and maternal IR are positively associated with children’s IR.

  16. Mild electrical stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling.

    Directory of Open Access Journals (Sweden)

    Saori Morino

    Full Text Available Low-intensity electrical current (or mild electrical stimulation; MES influences signal transduction and activates phosphatidylinositol-3 kinase (PI3K/Akt pathway. Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance. In addition, it was also previously reported that heat shock protein 72 (Hsp72 alleviates hyperglycemia. Thus, we applied MES in combination with heat shock (HS to in vitro and in vivo models of insulin resistance. Here we show that 10-min treatment with MES at 5 V (0.1 ms pulse duration together with HS at 42 degrees C increased the phosphorylation of insulin signaling molecules such as insulin receptor substrate (IRS and Akt in HepG2 cells maintained in high-glucose medium. MES (12 V+mild HS treatment of high fat-fed mice also increased the phosphorylation of insulin receptor beta subunit (IRbeta and Akt in mice liver. In high fat-fed mice and db/db mice, MES+HS treatment for 10 min applied twice a week for 12-15 weeks significantly decreased fasting blood glucose and insulin levels and improved insulin sensitivity. The treated mice showed significantly lower weight of visceral and subcutaneous fat, a markedly improved fatty liver and decreased size of adipocytes. Our findings indicated that the combination of MES and HS alleviated insulin resistance and improved fat metabolism in diabetes mouse models, in part, by enhancing the insulin signaling pathway.

  17. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin resistant phenotypes

    DEFF Research Database (Denmark)

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas;

    2013-01-01

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance, however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization......) and were instructed to maintain a eucaloric diet. A euglycemic-hyperinsulinemic clamp (40 mU/m(2)/min) with [6,6-(2)H]-glucose was used to determine peripheral and hepatic insulin sensitivity. Non-oxidative glucose disposal and metabolic flexibility (insulin-stimulated respiratory quotient [RQ] minus...

  18. Xylitol prevents NEFA-induced insulin resistance in rats

    Science.gov (United States)

    Kishore, P.; Kehlenbrink, S.; Hu, M.; Zhang, K.; Gutierrez-Juarez, R.; Koppaka, S.; El-Maghrabi, M. R.

    2013-01-01

    Aims/hypothesis Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance. Methods We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic–hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol. Results Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol. Conclusions/interpretation We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects. PMID:22460760

  19. Relations between obesity, insulin resistance, and 25-hydroxyvitamin D123

    OpenAIRE

    Lamendola, Cynthia A; Ariel, Danit; Feldman, David; Reaven, Gerald M.

    2012-01-01

    Background: Although low circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance and obesity, the relations between these 3 variables have not been completely resolved.

  20. Early insulin resistance in severe trauma without head injury as outcome predictor? A prospective, monocentric pilot study

    Directory of Open Access Journals (Sweden)

    Bonizzoli Manuela

    2012-10-01

    Full Text Available Abstract Background Hyperglycemia following major trauma is a well know phenomenon related to stress-induced systemic reaction. Reports on glucose level management in patients with head trauma have been published, but the development of insulin resistance in trauma patients without head injury has not been extensively studied. The aim of this study was therefore to investigate the prognostic role of acute insulin-resistance, assessed by the HOMA model, in patients with severe trauma without head injury. Methods All patients consecutively admitted to the Intensive Care Unit (ICU of a tertiary referral center (Careggi Teaching Hospital, Florence, IT for major trauma without head injury (Jan-Dec 2010 were enrolled. Patients with a previous diagnosis of diabetes mellitus requiring insulin therapy or metabolism alteration were excluded from the analysis. Patients were divided into “insulin resistant” and “non-insulin resistant” based on the Homeostasis Model Assessment index (HOMA IR. Results are expressed as medians. Results Out of 175 trauma patients admitted to the ICU during the study period, a total of 54 patients without head trauma were considered for the study, 37 of whom met the inclusion criteria. In total, 23 patients (62.2% resulted insulin resistant, whereas 14 patients (37.8% were non-insulin resistant. Groups were comparable in demographic, clinical/laboratory characteristics, and severity of injury. Insulin resistant patients had a significantly higher BMI (P=0.0416, C-reactive protein (P=0.0265, and leukocytes count (0.0301, compared to non-insulin resistant patients. Also ICU length of stay was longer in insulin resistant patients (P=0.0381. Conclusions Our data suggest that admission insulin resistance might be used as an early outcome predictor.

  1. Insulin resistance and exercise tolerance in heart failure patients

    DEFF Research Database (Denmark)

    Snoer, Martin; Monk-Hansen, Tea; Olsen, Rasmus Huan;

    2012-01-01

    Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage.......Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage....

  2. Disruption of Adipose Rab10-Dependent Insulin Signaling Causes Hepatic Insulin Resistance.

    Science.gov (United States)

    Vazirani, Reema P; Verma, Akanksha; Sadacca, L Amanda; Buckman, Melanie S; Picatoste, Belen; Beg, Muheeb; Torsitano, Christopher; Bruno, Joanne H; Patel, Rajesh T; Simonyte, Kotryna; Camporez, Joao P; Moreira, Gabriela; Falcone, Domenick J; Accili, Domenico; Elemento, Olivier; Shulman, Gerald I; Kahn, Barbara B; McGraw, Timothy E

    2016-06-01

    Insulin controls glucose uptake into adipose and muscle cells by regulating the amount of GLUT4 in the plasma membrane. The effect of insulin is to promote the translocation of intracellular GLUT4 to the plasma membrane. The small Rab GTPase, Rab10, is required for insulin-stimulated GLUT4 translocation in cultured 3T3-L1 adipocytes. Here we demonstrate that both insulin-stimulated glucose uptake and GLUT4 translocation to the plasma membrane are reduced by about half in adipocytes from adipose-specific Rab10 knockout (KO) mice. These data demonstrate that the full effect of insulin on adipose glucose uptake is the integrated effect of Rab10-dependent and Rab10-independent pathways, establishing a divergence in insulin signal transduction to the regulation of GLUT4 trafficking. In adipose-specific Rab10 KO female mice, the partial inhibition of stimulated glucose uptake in adipocytes induces insulin resistance independent of diet challenge. During euglycemic-hyperinsulinemic clamp, there is no suppression of hepatic glucose production despite normal insulin suppression of plasma free fatty acids. The impact of incomplete disruption of stimulated adipocyte GLUT4 translocation on whole-body glucose homeostasis is driven by a near complete failure of insulin to suppress hepatic glucose production rather than a significant inhibition in muscle glucose uptake. These data underscore the physiological significance of the precise control of insulin-regulated trafficking in adipocytes. PMID:27207531

  3. Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

    OpenAIRE

    De Moura, Leandro Pereira; Souza Pauli, Luciana Santos; Cintra, Dennys Esper; de Souza, Claudio Teodoro; da Silva, Adelino Sanchez Ramos; Marinho, Rodolfo; de Melo, Maria Alice Rostom; Ropelle, Eduardo Rochete; Pauli, José Rodrigo

    2013-01-01

    It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the ...

  4. Effect of dehydroepiandrosterone on insulin action and development of insulin-induced resistance in C2C12 muscle cells

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Dehydroepiandrosterone (DHEA), a precursor of androgens and estrogens, has been demonstrated to have effect of preventing insulin resistance and development of diabetes mellitus. Administration of testosterone appears to induce a marked insulin resistance. How these two hormones affect insulin resistance through regulation of sensitivity of tissues to insulin deserves further studies. Here, the effects of DHEA and testosterone on response to insulin in C2C12 muscle cells are analyzed. After 24 h of DHEA (10-6 mol/L) treatment, C2C12 cells showed an increased insulin- stimulated glucose uptake and enhanced activities of glycogen synthase (GS), phosphofructokinase (PFK) and pyruvate dehydrogenase (PDH), whereas testosterone gave the opposite effects. Incubation of C2C12 cells with high-dose insulin (5×10-7 mol/L) for 24 hours decreased their sensitivity to insulin and led to a state of resistance as assessed on insulin-stimulated glucose uptake and activities of GS, PFK and PDH. Addition of DHEA to insulin-resistant C2C12 cells could reverse the response of these cells to high-dose insulin, but testosterone could further impair insulin sensitivity in insulin-resistant C2C12 cells. These results suggest that the two hormones may influence the development or inhibition of insulin-resistance in type 2 diabetes through regulating glucose uptake, glycogenesis and glycolysis to some extent.

  5. Association of resistin with visceral fat and muscle insulin resistance.

    Science.gov (United States)

    Borst, Stephen E; Conover, Christine F; Bagby, Gregory J

    2005-10-01

    Maturing Sprague-Dawley (S-D) rats develop obesity and skeletal muscle insulin resistance. To investigate the relationship between fat mass and insulin responses, we performed surgical removal of the epididymal and retroperitoneal depots of visceral adipose tissue (VF) or sham surgery (SHAM) in male rats aged 4 months. At sacrifice, 30 days later, the mass of visceral fat was 48% lower (pfat was essentially unchanged. VF- animals displayed increased insulin responses in isolated strips of skeletal muscle. Insulin-stimulated glucose transport was increased 28% in soleus muscle (pfat removal. In VF- animals, serum resistin was reduced 26% (pvisceral adiposity leads to an increase in systemic release in resistin and possibly interleukins. Elevation of circulating cytokines may play a role in the development of muscle insulin resistance. PMID:16154759

  6. INFLUENCE OF ACUPUNCTURE ON INSULIN RESISTANCE IN OBESITY PATIENTS

    Institute of Scientific and Technical Information of China (English)

    YI Wei; XU Nenggui; JIN Rui

    2002-01-01

    Aims: To investigate the influence of acupuncture on insulin resistance in obesity patients. Methods: In treatment group, 20 obesity patients were treated with acupuncture of Neiguan (PC 6), Zusanli (ST 36), Daimai (GB 26), Sanyinjiao (SP 6), Zhongwan (CV 12), etc.. In control group, 12 normal volunteer subjects were observed.The obesity index, fasting blood sugar (FPG), plasma insulin (FINS) and C-peptide contents, and insulin sensitive index (ISI) were measured before and after acupuncture treatment. Results: Before treatment in comparison with control group, FPG, FINS and C-peptide of obesity patients were significant higher (P < 0.01 ), while ISI was considerably lower ( P< 0.01 ); after acupuncture treatment, the levels of plasma insulin and C peptide decreased obviously, ISI increased markedly (P < 0.01 ), and the obesity index was considerably improved with a total effective rate of 85 %.Conclusion: Acupuncture can alleviate obesity and improve insulin resistance.

  7. Association of sleep duration and insulin resistance in Taiwanese vegetarians

    Directory of Open Access Journals (Sweden)

    Chang Jiunn-Kae

    2012-08-01

    Full Text Available Abstract Background Short sleep duration has been reported to associate with increased insulin resistance. However, no studies have investigated whether such association exists in vegetarians. The aim of this study was to investigate the association between sleep duration and insulin resistance in Taiwanese vegetarians. Methods A total of 1290 individuals were recruited from a regional hospital in south Taiwan during their regular routine physical examination. Only individuals who described themselves as Buddhist vegetarians were included in the study. Demographic information and clinical characteristics were collected and multiple logistic regression analysis was used to evaluate the association between sleep duration and insulin resistance. Results A total of 433 vegetarians were included in the study. Results from univariate logistic regression indicated that insulin resistance was significantly associated with male sex, greater waist circumference, higher triglyceride levels, lower high-density lipoprotein cholesterol levels, higher plasma creatinine levels, higher alanine transaminase levels, greater energy expenditure, and sleep duration of more than 8 hours per night. Multiple logistic regression revealed that insulin resistance was significantly and independently associated with sleep duration of more than 8 hours per night (odd ratios = 2.27, 95% confidence interval = 1.24, 4.11 after adjusting for waist circumference and levels of alanine transaminase. Conclusions Sleep duration of more than 8 hours per night is an independent risk factor associated with increased insulin resistance in vegetarians.

  8. Higher fetal insulin resistance in Chinese pregnant women with gestational diabetes mellitus and correlation with maternal insulin resistance.

    Directory of Open Access Journals (Sweden)

    Qiuwei Wang

    Full Text Available OBJECTIVE: The aim of this study was to determine the effect of gestational diabetes mellitus (GDM on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. MEASUREMENTS: Maternal fasting blood and venous cord blood samples (reflecting fetal condition were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function were calculated in maternal and cord blood respectively. RESULTS: Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively. Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019, in the pregnant women with GDM. CONCLUSIONS: Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.

  9. Human primary myoblast cell cultures from non-diabetic insulin resistant subjects retain defects in insulin action.

    OpenAIRE

    Thompson, D B; Pratley, R; Ossowski, V

    1996-01-01

    Insulin resistance is a predictor of the development of noninsulin-dependent diabetes mellitus (NIDDM) in humans. It is unclear whether insulin resistance is a primary defect leading to NIDDM or the result of hyperinsulinemia and hyperglycemia. To determine if insulin resistance is the result of extrinsic factors such as hyperinsulinemia primary skeletal muscle cell cultures were established from muscle biopsies from Pima Indians with differing in vivo insulin sensitivities. These cell cultur...

  10. Interleukin-6 and insulin resistance in obese adolescents

    Directory of Open Access Journals (Sweden)

    Raynald Takumansang

    2013-09-01

    Full Text Available Background Obesity has become a rapidly growing epidemic worldwide, increasing the risk of morbidity and mortality in adolescents. is due to an expansion of adipose tissue mass, which is an important source of cytokines and contributes to an increase in pro-inflammatory cytokines, such as interleukin-6 (IL-6. Interleukin-6 is significantly increased in obesity and may lead to a state of insulin resistance. Objective To assess for a correlation between IL-6 levels and insulin resistance in obese adolescents Methods We conducted a cross-sectional study from January to April 2012 in Manado, North Sulawesi. Subjects were either obese or normal body mass index (BMI teens aged 13-18 years. Data collected were anthropometric status, BMI, and blood specimens for fasting plasma glucose levels, fasting insulin levels, and ILl-6 levels. Insulin resistance was expressed as homeostatic model assessment of insulin resistance (HOMA-IR level >2.77. Data was analyzed by Pearson’s correlation and linear regression tests to assess for a possible correlation between IL-6 levels and insulin resistance. Results The mean BMI in the obese group was 31.21 (SD 3.61 kg/m2 while the mean BMI in the normal group was 19.52 (SD 2.38 kg/m2. There was no significant association between IL-6 and the occurrence of insulin resistance (P=0.309. The log regression coefficient value of IL-6 was negative (b = -0.329. Conclusion There is no correlation between IL-6 levels and incidence of insulin resistance in obese adolescents.[Paediatr Indones. 2013;53:268-72.].

  11. Predictors of insulin resistance in pediatric burn injury survivors 24 to 36 months post-burn

    Science.gov (United States)

    Chondronikola, Maria; Meyer, Walter J.; Sidossis, Labros S.; Ojeda, Sylvia; Huddleston, Joanna; Stevens, Pamela; Børsheim, Elisabet; Suman, Oscar E.; Finnerty, Celeste C.; Herndon, David N.

    2014-01-01

    Background Burn injury is a dramatic event with acute and chronic consequences including insulin resistance. However, factors associated with insulin resistance have not been previously investigated. Purpose To identify factors associated with long-term insulin resistance in pediatric burn injury survivors. Methods The study sample consisted of 61 pediatric burn injury survivors 24 to 36 months after the burn injury, who underwent an oral glucose tolerance test. To assess insulin resistance, we calculated the area under the curve for glucose and insulin. The diagnostic criteria of the American Diabetes Association were used to define individuals with impaired glucose metabolism. Additional data collected include body composition, anthropometric measurements, burn characteristics and demographic information. The data were analyzed using multivariate linear regression analysis. Results Approximately 12% of the patients met the criteria for impaired glucose metabolism. After adjusting for possible confounders, burn size, age and percent body fat were associated with the area under the curve for glucose (p<0.05 for all). Time post-burn and lean mass were inversely associated with the area under the curve for glucose (p<0.05 for both). Similarly, older age predicted higher insulin area under the curve. Conclusion A significant proportion of pediatric injury survivors suffer from glucose abnormalities 24–36 months post-burn. Burn size, time post-burn, age, lean mass and adiposity are significant predictors of insulin resistance in pediatric burn injury survivors. Clinical evaluation and screening for abnormal glucose metabolism should be emphasized in patients with large burns, older age and survivors with high body fat. PMID:24918945

  12. Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women

    DEFF Research Database (Denmark)

    Schmiegelow, Michelle D; Hedlin, Haley; Stefanick, Marcia L;

    2015-01-01

    studies with no history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993-1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-high-density lipoprotein-cholesterol ratio TG....../HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which.......98-1.15); for TG/HDL-C, 1.11 (CI, 0.99-1.25); and for glucose, 1.20 (CI, 0.96-1.50). Insulin resistance measures did not improve CVD risk discrimination and reclassification. CONCLUSIONS: Measures of insulin resistance were no longer associated with CVD risk after adjustment for high-density lipoprotein-cholesterol...

  13. Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

    DEFF Research Database (Denmark)

    Ruzzin, Jérôme; Petersen, Rasmus; Meugnier, Emmanuelle;

    2010-01-01

    of persistent organic pollutants (POPs). However, experimental evidence demonstrating a causal link between POPs and the development of insulin resistance is lacking. OBJECTIVE: We investigated whether exposure to POPs contributes to insulin resistance and metabolic disorders. METHODS: Wistar rats were exposed...... for 28 days to lipophilic POPs through the consumption of high-fat diet containing either refined or crude fish oil obtained from farmed Atlantic salmon. Furthermore, differentiated adipocytes were exposed to several POP mixtures that mimicked the relative abundance of organic pollutants present in crude...... salmon oil. We measured body weight, whole-body insulin sensitivity, POP accumulation, lipid and glucose homeostasis, gene expression and performed microarray analysis. RESULTS: Adult male rats exposed to crude, but not refined, salmon oil developed insulin resistance, abdominal obesity...

  14. The gut microbiota, obesity and insulin resistance.

    Science.gov (United States)

    Shen, Jian; Obin, Martin S; Zhao, Liping

    2013-02-01

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate

  15. Conventional insulin vs insulin infusion therapy in acute coronary syndrome diabetic patients

    Institute of Scientific and Technical Information of China (English)

    Caterina; Arvia; Valeria; Siciliano; Kyriazoula; Chatzianagnostou; Gillian; Laws; Alfredo; Quinones; Galvan; Chiara; Mammini; Sergio; Berti; Sabrina; Molinaro; Giorgio; Iervasi

    2014-01-01

    AIM:To evaluate the impact on glucose variability(GLUCV)of an nurse-implemented insulin infusion protocol when compared with a conventional insulin treatment during the day-to-day clinical activity.METHODS:We enrolled 44 type 2 diabetic patients(n=32 males;n=12 females)with acute coronary syndrome(ACS)and randomy assigned to standard a subcutaneous insulin treatment(n=23)or a nurse-implemented continuous intravenous insulin infusion protocol(n=21).We utilized some parameters of GLUCV representing well-known surrogate markers of prognosis,i.e.,glucose standard deviation(SD),the mean dailyδglucose(mean of daily difference between maximum and minimum glucose),and the coefficient of variation(CV)of glucose,expressed as percent glucose(SD)/glu-cose(mean).RESULTS:At the admission,first fasting blood glucose,pharmacological treatments(insulin and/or anti-diabetic drugs)prior to entering the study and basal glycated hemoglobin(HbA1c)were observed in the two groups treated with subcutaneous or intravenous insulin infusion,respectively.When compared with patients submitted to standard therapy,insulin-infused patients showed both increased first 24-h(median 6.9 mmol/L vs 5.7mmol/L P<0.045)and overall hospitalizationδglucose(median 10.9 mmol/L vs 9.3 mmol/L,P<0.028),with a tendency to a significant increase in first 24-h glycaemic CV(23.1%vs 19.6%,P<0.053).Severe hypoglycaemia was rare(14.3%),and it was observed only in 3 patients receiving insulin infusion therapy.HbA1c values measured during hospitalization and 3 mo after discharge did not differ in the two groups of treatment.CONCLUSION:Our pilot data suggest that no real benefit in terms of GLUCV is observed when routinely managing blood glucose by insulin infusion therapy in type 2 diabetic ACS hospitalized patients in respect to conventional insulin treatment

  16. An acute bout of endurance exercise but not sprint interval exercise enhances insulin sensitivity.

    Science.gov (United States)

    Brestoff, Jonathan R; Clippinger, Benjamin; Spinella, Thomas; von Duvillard, Serge P; Nindl, Bradley C; Nindl, Bradley; Arciero, Paul J

    2009-02-01

    An acute bout of endurance exercise (EE) enhances insulin sensitivity, but the effects of sprint interval exercise (SIE) have not yet been described. We sought to compare insulin sensitivity at baseline and after an acute bout of EE and SIE in healthy men (n = 8) and women (n = 5) (age, 20.7 +/- 0.3 years; peak oxygen consumption (VO2 peak), 42.6 +/- 1.7 mL.kg(-1).min(-1); men vs. women, p > 0.05). Pearson's correlation coefficients between ISI-COMP and ISI-HOMA for each condition were highly correlated (p < 0.01), and followed similar patterns of response. ISI-COMP(EE) was 71.4% higher than ISI-COMP(B) (8.4 +/- 1.4 vs. 4.9 +/- 1.0; p < 0.01) and 40.0% higher than ISI-COMPSIE (8.4 +/- 1.4 vs. 6.0 +/- 1.5; p < 0.05), but there was no difference between ISI-COMP(B) and ISI-COMP(SIE) (p = 0.182). VO(2 peak) was highly correlated with both ISI-COMP and ISI-HOMA during baseline and SIE test conditions (p < 0.02). These findings demonstrate that an acute bout of EE, but not SIE, increases insulin sensitivity relative to a no-exercise control condition in healthy males and females. While these findings underscore the use of regular EE as an effective intervention strategy against insulin resistance, additional research examining repeated sessions of SIE on insulin sensitivity is warranted.

  17. Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

    DEFF Research Database (Denmark)

    de Rooij, Susanne R; Dekker, Jacqueline M; Kozakova, Michaela;

    2009-01-01

    of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis. RESULTS: Fasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds...... ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8-10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6-9.9) in women. The odds ratio for metabolic syndrome of those with insulin......OBJECTIVE: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. DESIGN AND METHODS: The Relationship between Insulin...

  18. Insulin resistance, insulin response, and obesity as indicators of metabolic risk

    DEFF Research Database (Denmark)

    Ferrannini, Ele; Balkau, Beverley; Coppack, Simon W;

    2007-01-01

    CONTEXT: Insulin resistance (IR) and obesity, especially abdominal obesity, are regarded as central pathophysiological features of a cluster of cardiovascular risk factors (CVRFs), but their relative roles remain undefined. Moreover, the differential impact of IR viz. insulin response has not been...... evaluated. OBJECTIVE: The objective of this study was to dissect out the impact of obesity, abdominal obesity, and IR/insulin response on CVRF. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at 21 research centers in Europe. SUBJECTS: The study included a cohort of 1308...... nondiabetic subjects [718 women and 590 men, age 30-60 yr, body mass index (BMI) 17-44 kg.m(-2)]. MAIN OUTCOME MEASURES: We measured IR (by a standardized euglycemic insulin clamp), waist girth, insulin response to an oral glucose tolerance test, and major CVRF, and analyzed their associations by multivariate...

  19. Assessment of insulin resistance in normoglycemic young adults.

    Science.gov (United States)

    Preethi, B L; Jaisri, G; Kumar, K M Prasanna; Sharma, Rajeev

    2011-01-01

    Detection of Insulin resistance (IR) in normoglycemic young subjects before the onset of Impaired Glucose Tolerance (IGT) is of importance as it affords implementation of preventive measures in such high risk subject. Very few studies have specifically evaluated for the presence of IR in younger age group with normal glucose tolerance. The gold standard for investigating and quantifying insulin resistance is the "hyperinsulinemic euglycemic clamp," the complicated nature of the "clamp" technique, alternatives have been sought to simplify the measurement of insulin resistance. The oral glucose tolerance test (OGTT) is one of the most commonly used methods to evaluate whole body glucose tolerance in vivo. IR & IS values of HOMA-IR, ISI 0-120, QUICKIE mathematical models derived from OGTT have been shown to produce equivalent results as in Euglycemic clamp technique we hypothesized that normoglycemic young adult who are siblings of type II diabetics (SD) probably have higher IR values than the siblings of non diabetics as they are genetically predisposed. In this study 79 normal young adult volunteers, 40 subjects with family history of diabetes (SD) and 39 subjects without family history of diabetes (SND), in the age range of 18 to 25 years were evaluated for Insulin resistance. Standard (75 g) OGTT was performed on all the study subjects after an overnight fast. Fasting (basal), 30, 120 min venous plasma glucose & Corresponding specific insulin concentration was determined by radioimmuno assay (RIA) using a human specific antibody RIA kit. In each subject, the degree of insulin resistance was estimated by various parameters of Insulin resistance & sensitivity that were calculated using physiological mathematical models like HOMA-IR, ISI0-120, IGI, QUICKIE and their formulas derived from OGTT. The mean age of the study population was 19.01 (18 to 25 years), Male: 33 (41.3%) and Female: 47 (58.8%). The normoglycemic subjects were categorized as Siblings of Diabetics

  20. Association of insulin resistance with obesity in children

    International Nuclear Information System (INIS)

    Background: Insulin resistance is the primary metabolic disorder associated with obesity. Little is known about its role as a determinant of the metabolic syndrome in obese children. Objectives: To assess the association of insulin resistance with metabolic syndrome in obese and non obese children. Study type and settings: Cross sectional analytical study conducted among children of ten Municipal Corporation high schools of Data Ganj Buksh Town Lahore. Subjects and Methods: A total of 46 obese and 49 non obese children with consent were recruited for the study. Fasting blood glucose, serum insulin, high density lipoprotein in cholesterol, triglycerides, cholesterol, non HDL-cholesterol LDL-cholesterol were measured using standard methods. Data were analyzed by using statistical software SPSS-Version 15. Results: A total of 95 children 49 obese and 46 non obese were recruited for the study. A significant association of serum triglyceride(p<0.001), high density lipoprotein cholesterol(p<0.001), fasting blood glucose(p<0.001), and insulin levels (p<0.001) , was seen between the two groups. For each component of metabolic syndrome, when insulin resistance increased so did odds ratios for cardio metabolic risk factors. Conclusions: Insulin resistance was seen in 34.7% children. Metabolic syndrome was found in 31.6% children reflecting that obese children are at high risk for metabolic syndrome and have low HDL-cholesterol and high triglycerides levels. (author)

  1. Insulin Resistance in Human iPS Cells Reduces Mitochondrial Size and Function

    OpenAIRE

    Burkart, Alison M.; Tan, Kelly; Warren, Laura; Iovino, Salvatore; Hughes, Katelyn J.; Kahn, C. Ronald; Patti, Mary-Elizabeth

    2016-01-01

    Insulin resistance, a critical component of type 2 diabetes (T2D), precedes and predicts T2D onset. T2D is also associated with mitochondrial dysfunction. To define the cause-effect relationship between insulin resistance and mitochondrial dysfunction, we compared mitochondrial metabolism in induced pluripotent stem cells (iPSC) from 5 healthy individuals and 4 patients with genetic insulin resistance due to insulin receptor mutations. Insulin-resistant iPSC had increased mitochondrial number...

  2. Intrinsic Frequency and the Single Wave Biopsy: Implications for Insulin Resistance

    OpenAIRE

    Petrasek, Danny; Pahlevan, Niema M.; Tavallali, Peyman; Rinderknecht, Derek G.; Gharib, Morteza

    2015-01-01

    Insulin resistance is the hallmark of classical type II diabetes. In addition, insulin resistance plays a central role in metabolic syndrome, which astonishingly affects 1 out of 3 adults in North America. The insulin resistance state can precede the manifestation of diabetes and hypertension by years. Insulin resistance is correlated with a low-grade inflammatory condition, thought to be induced by obesity as well as other conditions. Currently, the methods to measure and monitor insulin res...

  3. Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion?

    OpenAIRE

    Scheen, André

    2005-01-01

    Elderly people are more glucose intolerant and insulin resistant than young individuals, and many of them will develop type 2 diabetes. It remains, however, controversial whether this decrease in function is due to an inevitable consequence of "biological aging" or due to environmental or lifestyle variables. Indeed, increased adiposity/altered fat distribution, decreased fat free mass/abnormal muscle composition, poor dietary habits and physical inactivity all contribute to reduce insulin se...

  4. Binge Drinking Induces Whole-Body Insulin Resistance by Impairing Hypothalamic Insulin Action

    OpenAIRE

    Lindtner, Claudia; Scherer, Thomas; Zielinski, Elizabeth; Filatova, Nika; Fasshauer, Martin; Tonks, Nicholas K.; Puchowicz, Michelle; Buettner, Christoph

    2013-01-01

    Individuals with a history of binge drinking have an increased risk of developing the metabolic syndrome and type 2 diabetes. Whether binge drinking impairs glucose homeostasis and insulin action is unknown. To test this, we treated Sprague-Dawley rats daily with alcohol (3 g/kg) for three consecutive days to simulate human binge drinking and found that these rats developed and exhibited insulin resistance even after blood alcohol concentrations had become undetectable. The animals were resis...

  5. Acute effects of 17 β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats.

    Science.gov (United States)

    Alonso, Ana; González-Pardo, Héctor; Garrido, Pablo; Conejo, Nélida M; Llaneza, Plácido; Díaz, Fernando; Del Rey, Carmen González; González, Celestino

    2010-12-01

    Aging is characterized by decline in metabolic function and insulin resistance, and both seem to be in the basis of neurodegenerative diseases and cognitive dysfunction. Estrogens prevent age-related changes, and phytoestrogens influence learning and memory. Our hypothesis was that estradiol and genistein, using rapid-action mechanisms, are able to modify insulin sensitivity, process of learning, and spatial memory. Young and aged ovariectomized rats received acute treatment with estradiol or genistein. Aged animals were more insulin-resistant than young. In each age, estradiol and genistein-treated animals were less insulin-resistant than the others, except in the case of young animals treated with high doses of genistein. In aged rats, no differences between groups were found in spatial memory test, showing a poor performance in the water maze task. However, young females treated with estradiol or high doses of genistein performed well in spatial memory task like the control group. Only rats treated with high doses of genistein showed an optimal spatial memory similar to the control group. Conversely, acute treatment with high doses of phytoestrogens improved spatial memory consolidation only in young rats, supporting the critical period hypothesis for the beneficial effects of estrogens on memory. Therefore, genistein treatment seems to be suitable treatment in aged rats in order to prevent insulin resistance but not memory decline associated with aging. Acute genistein treatment is not effective to restore insulin resistance associated to the early loss of ovarian function, although it can be useful to improve memory deficits in this condition. PMID:20467821

  6. Insulin Is a Stronger Inducer of Insulin Resistance than Hyperglycemia in Mice with Type 1 Diabetes Mellitus (T1DM)*

    OpenAIRE

    Liu, Hui-Yu; Cao, Sophia Y.; Hong, Tao; Han, Jianmin; Liu, Zhenqi; Cao, Wenhong

    2009-01-01

    Subjects with type 1 diabetes mellitus (T1DM) eventually develop insulin resistance and other features of T2DM such as cardiovascular disorders. The exact mechanism has been not been completely understood. In this study, we tested the hypothesis that excessive or inappropriate exposure to insulin is a primary mediator of insulin resistance in T1DM. We found that continuous exposure of mice with non-obese diabetes to insulin detemir, which is similar to some current conventional treatment of h...

  7. Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity in Insulin-Resistant Humans

    OpenAIRE

    Lalia, Antigoni Z; Johnson, Matthew L; Jensen, Michael D.; Hames, Kazanna C.; Port, John D.; Lanza, Ian R.

    2015-01-01

    OBJECTIVE Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and stimulate mitochondrial biogenesis in rodents, but the findings of translational studies in humans are thus far ambiguous. The aim of this study was to evaluate the influence of EPA and DHA on insulin sensitivity, insulin secretion, and muscle mitochondrial function in insulin-resistant, nondiabetic humans using a robust study design and gold-...

  8. Calpain-10 and insulin resistance in human skeletal muscle

    OpenAIRE

    Norton, Luke

    2007-01-01

    Variation in the calpain-10 gene has been linked to a three-fold increased risk for type 2 diabetes in Pima Indian and some European populations. Furthermore, reduced skeletal muscle expression of calpain-10 is associated with reduced insulin mediated glucose disposal and carbohydrate oxidation. The skeletal muscle specific calpain-3 plays a key role in skeletal muscle integrity and has also been linked to insulin resistance in humans and rodents. The major aims of this thesis were to...

  9. ADVANCES OF STUDIES ON ACUPUNCTURE TREATMENT OF INSULIN RESISTANCE

    Institute of Scientific and Technical Information of China (English)

    PENG Yan; HOU Li-hui; WU Xiao-ke

    2006-01-01

    Insulin resistance (IR) is referred to decrease or loss of reactivity of the insulin target organs and tissues to biological effects of insulin. It has been proved that IR is a common attack basis for diabetes,hypertension, obesity, cerebrovascular diseases, atherosclerosis and coronary heart disease. The unique therapeutic effects of acupuncture and moxibustion on IR are paid great attention to at home and abroad day by day. In this paper, the survey of studies on interfering action of acupuncture on IR diseases, the mechanisms of acupuncture and moxibustion in treatment of IR, and effects of acupuncture and moxibustion on energy metabolism is reviewed.

  10. Midkine, a potential link between obesity and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Nengguang Fan

    Full Text Available Obesity is associated with increased production of inflammatory mediators in adipose tissue, which contributes to chronic inflammation and insulin resistance. Midkine (MK is a heparin-binding growth factor with potent proinflammatory activities. We aimed to test whether MK is associated with obesity and has a role in insulin resistance. It was found that MK was expressed in adipocytes and regulated by inflammatory modulators (TNF-α and rosiglitazone. In addition, a significant increase in MK levels was observed in adipose tissue of obese ob/ob mice as well as in serum of overweight/obese subjects when compared with their respective controls. In vitro studies further revealed that MK impaired insulin signaling in 3T3-L1 adipocytes, as indicated by reduced phosphorylation of Akt and IRS-1 and decreased translocation of glucose transporter 4 (GLUT4 to the plasma membrane in response to insulin stimulation. Moreover, MK activated the STAT3-suppressor of cytokine signaling 3 (SOCS3 pathway in adipocytes. Thus, MK is a novel adipocyte-secreted factor associated with obesity and inhibition of insulin signaling in adipocytes. It may provide a potential link between obesity and insulin resistance.

  11. Pancreatic digestive enzyme blockade in the small intestine prevents insulin resistance in hemorrhagic shock.

    Science.gov (United States)

    DeLano, Frank A; Schmid-Schönbein, Geert W

    2014-01-01

    Hemorrhagic shock is associated with metabolic defects, including hyperglycemia and insulin resistance, but the mechanisms are unknown. We recently demonstrated that reduction of the extracellular domain of the insulin receptor by degrading proteases may lead to a reduced ability to maintain normal plasma glucose values. In shock, transfer of digestive enzymes from the lumen of the intestine into the systemic circulation after breakdown of the intestinal mucosal barrier causes inflammation and organ dysfunction. Suppression of the digestive enzymes in the lumen of the intestine with protease inhibitors is effective in reducing the level of the inflammatory reactions. To determine the degree to which blockade of digestive enzymes affects insulin resistance in shock, rats were exposed to acute hemorrhagic shock (mean arterial pressure of 30 mmHg for 2 h) at which time all shed blood volume was returned. Digestive proteases in the intestine were blocked with a serine protease inhibitor (tranexamic acid in polyethylene glycol and physiological electrolyte solution), and the density of the insulin receptor was measured with immunohistochemistry in the mesentery microcirculation. The untreated rat without enzyme blockade had significantly attenuated levels of insulin receptor density as compared with control and treated rats. Blockade of the digestive proteases after 60 min of hypotension in the lumen of the small intestine led to a lesser decrease in insulin receptor density compared with controls without protease blockade. Glucose tolerance test indicates a significant increase in plasma glucose levels 2 h after hemorrhagic shock, which are reduced to control values in the presence of protease inhibition in the lumen of the intestine. The transient reduction of the plasma glucose levels after an insulin bolus is significantly attenuated after shock but is restored when digestive enzymes in the lumen of the intestine are blocked. These results suggest that in

  12. Visceral adiposity, insulin resistance and cancer risk

    LENUS (Irish Health Repository)

    Donohoe, Claire L

    2011-06-22

    Abstract Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

  13. Immunometabolism of AMPK in insulin resistance and atherosclerosis.

    Science.gov (United States)

    Fullerton, Morgan D; Steinberg, Gregory R; Schertzer, Jonathan D

    2013-02-25

    Obesity leads to insulin resistance and atherosclerosis, which precede Type 2 diabetes and cardiovascular disease. Immunometabolism addresses how metabolic and inflammatory pathways converge to maintain health and a contemporary problem is determining how obesity-induced inflammation precipitates chronic diseases such as insulin resistance and atherosclerosis. AMP-activated protein kinase (AMPK) is an important serine/threonine kinase well known for regulating metabolic processes and maintaining energy homeostasis. However, both metabolic and immunological AMPK-mediated effects play a role in disease. Pro-inflammatory mediators suppress AMPK activity and hinder lipid oxidation. In addition, AMPK activation curbs inflammation by directly inhibiting pro-inflammatory signaling pathways and limiting the build-up of specific lipid intermediates that elicit immune responses. In the context of obesity and chronic disease, these reciprocal responses involve both immune and metabolic cells. Therefore, the immunometabolism of AMPK-mediated processes and therapeutics should be considered in atherosclerosis and insulin resistance. PMID:22361321

  14. Effect of gender on lipid-induced insulin resistance in obese subjects

    DEFF Research Database (Denmark)

    Vistisen, Bodil; Hellgren, Lars; Vadset, T.;

    2008-01-01

    Objective: In obese subjects, chronically elevated plasma concentrations of non-esterified fatty acids (NEFAs) exert a marked risk to contract insulin resistance and subsequently type 2 diabetes. When NEFA is acutely increased due to i.v. infusion of lipid, glucose disposal during...... a hyperinsulinemic-euglycemic clamp is reduced. This effect has been explained by a NEFA-induced decrease in skeletal muscle insulin sensitivity caused by accumulation of the lipid intermediates Such as ceramide and diacylglycerol in the myocytes. However, neither the lipid-induced reduction of glucose disposal nor...... the clamp was similar in females and males (46+/-10 and 60+/-4%,, respectively, NS). However, whole-body insulin sensitivity as well as non-oxidative glucose disposal was higher in obese females compared with obese males both during lipid and saline infusion (P...

  15. Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

    Science.gov (United States)

    Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

    2014-08-01

    The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition.

  16. Insulin resistance and occurrence and prognosis of ischemic stroke A non-randomized concurrent control and intra-group comparison

    Institute of Scientific and Technical Information of China (English)

    Xiaohong Zhao; Shaojun Jiang; Yue Tan

    2008-01-01

    factors for stroke, including hypertension and lipid metabolism disorder. Insulin resistance was correlated with the prognosis of acute cerebral infarction patients, but it was not an independent predictive factor.

  17. THE ROLE OF MAGNESIUM METABOLISM IN ESSENTIALHYPERTENSION WITH INSULIN RESISTANCE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To investigate the effects of magnesium metabolism and other positive ions in pathogenesis of essential hypertension(EH) patients with insulin resistance(IR). Methods The levels of Na+, K+, Ca2+, Mg2+ in erythrocyte and 24-hour urine samples were observed in 47 EH patients and in 30 subjects with normal blood pres sure. Insulin sensitivity index was used to evaluate the insulin sensitivity. Results In EH patients, the levels of K+ and Mg2+ in erythrocyte declined, but the levels of Na+ and Ca2+ in erythrocyte increased, and the 24-hour urinary excretion of Mg2+ reduced as compared to the subjects with normal blood pressure (P <0. 05). The levels of K+ and Mg2+ in erythrocyte of EH patients positively correlated with insulin sensitivity index, and the Mg2+ level in erythro cyte positively correlated with 24-hour urinary excretion of Ca2+ and Mg2+ , and the K+ level in erythrocyte. Conclu sion Abnormality of magnesium metabolism in EH patients may be the linking factor for hypertension and insulin re sistance, and may relate to inadequate intake of magnesium. Calcium and potassium may be involved in the occur rence of insulin resistance through affecting magnesium metabolism.

  18. Obesity-associated Gingival Vascular Inflammation and Insulin Resistance.

    Science.gov (United States)

    Mizutani, K; Park, K; Mima, A; Katagiri, S; King, G L

    2014-06-01

    Obesity is a risk factor for periodontitis, but the pathogenic mechanism involved is unclear. We studied the effects of insulin in periodontal tissues during the state of obesity-induced insulin resistance. Gingival samples were collected from fatty (ZF) and lean (ZL, control) Zucker rats. Endothelial nitric oxide synthase (eNOS) expression was decreased, and activities of protein kinase C (PKC) α, ß2, δ, and ϵ isoforms were significantly increased in the gingiva from ZF rats compared with those from ZL rats. Expression of oxidative stress markers (mRNA) and the p65 subunit of NF-κB was significantly increased in ZF rats. Immunohistochemistry revealed that NF-κB activation was also increased in the gingival endothelial cells from transgenic mice overexpressing NF-κB-dependent enhanced green fluorescent protein (GFP) and on a high-fat vs. normal chow diet. Analysis of the gingiva showed that insulin-induced phosphorylation of IRS-1, Akt, and eNOS was significantly decreased in ZF rats, but Erk1/2 activation was not affected. General PKC inhibitor and an anti-oxidant normalized the action of insulin on Akt and eNOS activation in the gingiva from ZF rats. This provided the first documentation of obesity-induced insulin resistance in the gingiva. Analysis of our data suggested that PKC activation and oxidative stress may selectively inhibit insulin-induced Akt and eNOS activation, causing endothelial dysfunction and inflammation. PMID:24744283

  19. Studies of insulin resistance in congenital generalized lipodystrophy

    DEFF Research Database (Denmark)

    Søvik, O; Vestergaard, H; Trygstad, O;

    1996-01-01

    Two well-characterized patients with congenital, generalized lipodystrophy have been studied by the euglycaemic hyperinsulinaemic clamp technique in combination with indirect calorimetry. Furthermore, glycogen synthase in muscle biopsies was studied in one patient with regard to enzyme activity...... suppressed lipid oxidation in the controls. It is concluded that patients with congenital generalized lipodystrophy may present severe insulin resistance with regard to hepatic glucose production as well as muscle glycogen synthesis and lipid oxidation. The results suggest a postreceptor defect in the action...... of insulin in congenital generalized lipodystrophy. The further localization of such a defect is hampered by the still incomplete understanding of the pathways that link insulin-stimulated tyrosine phosphorylation to the ultimate action of insulin upon target cells....

  20. Blood pressure, sodium intake, insulin resistance, and urinary nitrate excretion.

    Science.gov (United States)

    Facchini, F S; DoNascimento, C; Reaven, G M; Yip, J W; Ni, X P; Humphreys, M H

    1999-04-01

    The objective of this study was to investigate the relationships among various humoral factors thought to be involved in the regulation of blood pressure during high NaCl intake. Nineteen healthy subjects underwent sequential 5-day periods ingesting a low-sodium (25 mmol/d) or high-sodium (200 mmol/d) diet. Insulin resistance was assessed by the steady-state plasma glucose concentration at the end of a 3-hour insulin suppression test. Insulin resistance correlated inversely with natriuresis (P=0.04) and directly with increase in weight (P=0.03). The increase in mean arterial pressure associated with the high-sodium diet correlated directly with the gain in weight (P<0.05) and inversely with the increase in urinary nitrate excretion (P<0.0001). In a multiple regression model, more than 2/3 of the variance in mean arterial pressure was accounted for by the gain in weight and change in urinary nitrate excretion. The steady-state plasma glucose concentrations obtained with the 2 diets were similar, indicating that insulin resistance was unaffected by sodium intake. During high sodium intake, plasma renin activity and aldosterone decreased and plasma atrial natriuretic peptide increased; these changes did not correlate with the change in mean arterial pressure, insulin resistance, or change in urinary nitrate excretion. To the extent that urinary nitrate excretion reflects activity of the endogenous nitric oxide system, these results suggest that the salt sensitivity of mean arterial pressure may be related to blunted generation of endogenous nitric oxide. The results also demonstrate that insulin-resistant individuals have an impaired natriuretic response to high sodium intake. PMID:10205239

  1. Skeletal muscle insulin resistance is fundamental to the cardiometabolic syndrome.

    Science.gov (United States)

    Nistala, Ravi; Stump, Craig S

    2006-01-01

    The cardiometabolic syndrome is associated with insulin resistance and a dysregulation of glucose and lipid metabolism that occurs in multiple tissues. Of these, skeletal muscle is the most abundant insulin-sensitive tissue, handling > 40% of the postprandial glucose uptake, while consuming 20% of the body's energy. The inability to efficiently take up and store fuel, and to transition from fat to glucose as the primary source of fuel during times of plenty (increased insulin), has been termed metabolic inflexibility. This resistance to insulin is thought to be a major contributor to the whole-body metabolic dysregulation that leads to increased cardiovascular risk. Recent investigation has identified specific defects in postinsulin receptor signaling in skeletal muscle from resistant humans and animals. Potential mechanisms contributing to this reduced insulin signaling and action include decreases in mitochondrial oxidative capacity, increased intramuscular lipid accumulation, increased reactive oxygen species generation, and up-regulated inflammatory pathways. Future research is focused on understanding these and other potential mechanisms to identify therapeutic targets for reducing cardiometabolic syndrome risk. PMID:17675899

  2. Increased IL-1β activation, the culprit not only for defective insulin secretion but also for insulin resistance?

    Institute of Scientific and Technical Information of China (English)

    Marianne B(o)ni-Schnetzler; Marc Y Donath

    2011-01-01

    @@ Type 2 diabetes is a chronic progressive disease characterized by insufficient insulin secretion to compensate for insulin resistance.The onset of type 2 diabetes and its progression are mainly determined by the progressive failure of the pancreatic islet β-cells to produce sufficient levels of insulin.

  3. Role of PTEN in TNFα induced insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Bulger, David A. [Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States); Wellcome Trust Medical Research Council Institute of Metabolic Science, Cambridge CB2 0QQ (United Kingdom); National Institute of Diabetes & Digestive & Kidney Disease, National Institutes of Health, Bethesda, MD 20892 (United States); Conley, Jermaine [Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States); Conner, Spencer H.; Majumdar, Gipsy [Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States); Solomon, Solomon S., E-mail: ssolomon@uthsc.edu [Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States)

    2015-06-05

    Aims/hypothesis: PTEN may play a reversible role in TNFα induced insulin resistance, which has been linked to obesity-associated insulin resistance (IR). Methods: Western blots for PTEN and p-Akt were performed on H-411E liver cells incubated with insulin, TNFα, and in selected experiments VO-OHpic vanadium complex in the presence and absence of PTEN siRNA. Total PTEN was compared to β-actin loading control and p-Akt was compared to total Akt. Results: Western blot and Real Time RT-PCR experiments showed increased PTEN after TNFα treatment (p = 0.04); slightly decreased PTEN after insulin treatment; and slightly increased PTEN after insulin + TNFα treatment. PTEN siRNA markedly inhibited the TNFα-induced increase in PTEN (p < 0.01) without significantly changing the p-Akt levels. The vanadium complex, exhibiting insulin-like effects, also significantly prevented the TNFα-induced increase in PTEN. Combining insulin and VO-OHpic was additive, providing both proof of concept and insight into mechanism. Discussion: The PTEN increase due to TNFα treatment was reversible by both PTEN siRNA knockdown and VO-OHpic treatment. Thus, PTEN is identified as a potential new therapeutic target for reducing IR in Type 2 DM. - Highlights: • TNFα treatment induced a significant increase in PTEN in H-411E liver cells. • PTEN siRNA knockdown prevented this effect. • VO-OHpic (vanadium complex) treatment, like insulin, decreased PTEN protein levels. • Thus, PTEN is identified as a potential therapeutic target in DM Type 2.

  4. Role of PTEN in TNFα induced insulin resistance

    International Nuclear Information System (INIS)

    Aims/hypothesis: PTEN may play a reversible role in TNFα induced insulin resistance, which has been linked to obesity-associated insulin resistance (IR). Methods: Western blots for PTEN and p-Akt were performed on H-411E liver cells incubated with insulin, TNFα, and in selected experiments VO-OHpic vanadium complex in the presence and absence of PTEN siRNA. Total PTEN was compared to β-actin loading control and p-Akt was compared to total Akt. Results: Western blot and Real Time RT-PCR experiments showed increased PTEN after TNFα treatment (p = 0.04); slightly decreased PTEN after insulin treatment; and slightly increased PTEN after insulin + TNFα treatment. PTEN siRNA markedly inhibited the TNFα-induced increase in PTEN (p < 0.01) without significantly changing the p-Akt levels. The vanadium complex, exhibiting insulin-like effects, also significantly prevented the TNFα-induced increase in PTEN. Combining insulin and VO-OHpic was additive, providing both proof of concept and insight into mechanism. Discussion: The PTEN increase due to TNFα treatment was reversible by both PTEN siRNA knockdown and VO-OHpic treatment. Thus, PTEN is identified as a potential new therapeutic target for reducing IR in Type 2 DM. - Highlights: • TNFα treatment induced a significant increase in PTEN in H-411E liver cells. • PTEN siRNA knockdown prevented this effect. • VO-OHpic (vanadium complex) treatment, like insulin, decreased PTEN protein levels. • Thus, PTEN is identified as a potential therapeutic target in DM Type 2

  5. Delayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats.

    Science.gov (United States)

    Wascher, T C; Wölkart, G; Russell, J C; Brunner, F

    2000-05-01

    Capillary endothelial cells are thought to limit the transport of insulin across the endothelium, resulting in attenuated insulin action at target sites. Whether endothelial insulin transport is altered in dysglycemic insulin-resistant states is not clear and was therefore investigated in the JCR:LA-cp corpulent male rat, which exhibits the metabolic syndrome of obesity, insulin resistance, hyperlipidemia, and hyperinsulinemia. Lean littermates that did not develop these alterations served as controls. Animals of both groups were normotensive (mean arterial pressure 136+/-2 mmHg). Hearts from obese and lean rats aged 7 (n = 6) or 18 (n = 8) weeks were perfused in vitro at 10 ml/min per gram wet wt over 51 min with Krebs-Henseleit buffer containing 0.1 or 0.5 U human insulin/l (equivalent to 0.6 and 3 nmol/l). Interstitial fluid was collected using a validated method, and interstitial insulin was determined with a radioimmunoassay. At 0.1 U/l, insulin transfer velocity was similar in both experimental groups (half-times of transfer: 11+/-0.2 min in obese and 18+/-4 min in lean rats; NS), but at 0.5 U/l, the respective half-times were 7+/-1 min in lean and 13+/-2 min in obese rats (P < 0.05). The steady-state level of insulin in the interstitium was 34+/-1% of the vascular level at 0.1 U/l and reached the vascular level (102+/-2%) at 0.5 U/l in both lean and obese rats. In rats aged 18 weeks, the half-times of insulin transfer were 31+/-2 and 14+/-l min in obese rats and 10+/-0.3 and 7+/-0.3 min in lean rats (P < 0.05). Again, interstitial steady-state levels were similar in both groups. Finally, postprandial insulin dynamics were simulated over a period of 120 min with a peak concentration of 0.8 U/l in rats aged 27 weeks (n = 4). The maximal interstitial level was 0.38+/-0.02 U/l in lean rats and 0.24+/-0.02 U/l in obese rats (P < 0.05), and a similar difference was noted throughout insulin infusion (areas under the transudate concentration-time curves: 17 and 11 U

  6. Relationship of serum resistin with insulin resistance and obesity

    International Nuclear Information System (INIS)

    Background: Adipokines have been implicated in the modulation of insulin sensitivity and glucose tolerance and have thus gained importance in the study of Type 2 diabetes mellitus (T2DM). Resistin, a unique signalling molecule, is being proposed as a significant factor in the pathogenesis of obesity-related insulin resistance. However, its relevance to human diabetes mellitus remains uncertain and controversial. This study was therefore planned to compare and correlate the potential role of resistin in obese patients with T2DM and obese non-diabetic controls and also to evaluate the correlation between resistin and marker of obesity and glycaemic parameters. Method: Fasting serum resistin, glucose and insulin were measured in forty obese diabetics (mean±SD BMI 35±5 kg/m2) and forty obese non-diabetics (mean±SD BMI 33±3 kg/m2). Insulin resistance was assessed using the HOMA-IR formula derived from fasting insulin and glucose levels. Results: Serum resistin levels (38±8 ng/ml) were significantly higher in type 2 diabetic patients as compared with the controls. Fasting blood glucose (164±46 mg/dl), serum insulin (37±7 μU/ml) and insulin resistance (19±8), were considerably higher among the studied diabetics than in the controls. Pearson's correlation analysis revealed positive correlation between serum resistin and BMI (p=0.001) and HOMA-IR (p=0.561) in diabetic subjects. Similarly, a correlation also existed between serum resistin and BMI (p=0.016) and HOMA-IR (p=0.307) in control obese subjects. However, it was highly significant in diabetics as compared to non-diabetic controls. Conclusion: A significant BMI-dependent association exists between resistin and insulin resistance in patients with T2DM. It appears that resistin may play a role in the pathogenesis of obesity and insulin resistance and that both of these may contribute to the development of T2DM. (author)

  7. Relationship of Insulin Sensitivity, Insulin Secretion, and Adiposity With Insulin Clearance in a Multiethnic Population

    OpenAIRE

    Lorenzo, Carlos; Hanley, Anthony J.G.; Wagenknecht, Lynne E; Rewers, Marian J.; Stefanovski, Darko; Goodarzi, Mark O.; Haffner, Steven M

    2012-01-01

    OBJECTIVE We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance. RESEARCH DESIGN AND METHODS We measured insulin sensitivity index (S I), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study. RESULTS MCRI was positive...

  8. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, K.B.; Smit, J.W.A.; Heijer, M. den; Middeldorp, S.; Rippe, R.C.; Cessie, S. le; Koning, E.J. de; Jukema, J.W.; Rabelink, T.J.; Roos, A. de; Rosendaal, F.R.; Mutsert, R. de; Assendelft, P.

    2013-01-01

    OBJECTIVE: The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  9. Cancer-drug induced insulin resistance : Innocent bystander or unusual suspect

    NARCIS (Netherlands)

    Ariaans, G.; de Jong, S.; Gietema, J. A.; Lefrandt, J. D.; de Vries, E. G. E.; Jalving, M.

    2015-01-01

    Epidemiological and experimental evidence strongly suggests an association between type 2 diabetes mellitus and cancer. Insulin resistance, causing hyperinsulinaemia and eventually hyperglycaemia, appears to increase cancer incidence and disease progression. In addition, insulin resistance seems to

  10. Insulin resistance and postreceptor changes of liver metabolism in fat-fed mice

    DEFF Research Database (Denmark)

    Hedeskov, Carl Jørgen; Capito, Kirsten; Hansen, Svend Erik;

    1992-01-01

    Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet......Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet...

  11. Influence of magnesium on insulin resistance in obese women.

    Science.gov (United States)

    Cruz, Kyria Jayanne Clímaco; de Oliveira, Ana Raquel Soares; Pinto, Denise Pereira; Morais, Jennifer Beatriz Silva; Lima, Fabiana da Silva; Colli, Célia; Torres-Leal, Francisco Leonardo; Marreiro, Dilina do Nascimento

    2014-09-01

    The present study evaluated the influence of magnesium on insulin resistance in obese women. A case-control study involving 114 women on the age between 20 and 50 years old, divided into two groups: control (eutrophic women, n = 59) and case (obese women, n = 55). The analysis of magnesium intake was carried out through the 3-day food record and also NutWin software version 1.5. The plasma, erythrocyte, and urinary magnesium concentrations were determined by flame atomic absorption spectrophotometry. The determinations of serum glucose and serum insulin were performed by enzymatic colorimetric method and chemiluminescence, respectively. The insulin resistance was assessed by homeostasis model assessment insulin resistance (HOMA-IR). The mean values of magnesium intake were lower than those recommended, without difference between groups (p > 0.05). All the patients who were evaluated showed adequate mean concentrations of magnesium in the plasma and erythrocyte. The urinary excretion of this mineral was lower than the reference values in both groups and did not show significant difference (p > 0.05). The values of serum glucose, serum insulin, and HOMA-IR were higher in obese women compared to the control group. A negative correlation was observed between erythrocyte magnesium and glycemic parameters (p magnesium content, and they show hypomagnesuria as a compensatory mechanism to keep the plasma concentration of this mineral in adequate levels. The correlation between the erythrocyte magnesium concentration and the parameters of glycemic control suggests the influence of this mineral on the index of insulin resistance in obese women.

  12. Insulin resistance in sub clinical hypothyroidism

    Directory of Open Access Journals (Sweden)

    Shyam Rameshwar Adhau

    2015-06-01

    Results: HOMA-IR values showed highly significant association between controls and SCH. TSH levels were positively correlated with insulin and HOMA IR in patients with SCH. Conclusions: Therefore, it will be good practice to screen people and Type 2 DM patients for presence of SCH, so that early detection and prompt intervention can prevent or prolong the appearance of various fatal complications associated with IR and help in managing diabetes holistically. [Int J Res Med Sci 2015; 3(6.000: 1420-1425

  13. ASSOCIATION BETWEEN ADIPONECTIN, INSULIN RESISTANCE, AND ENDOMETRIAL CANCER

    Science.gov (United States)

    BACKGROUND: Obesity is a well-known risk factor for the development of endometrial cancer; however, weight alone does not account for all cases. The authors hypothesized that insulin resistance also contributes to an increased risk for endometrial cancer. Adiponectin is a protein secreted by adipose...

  14. Neuroendocrinology of insulin resistance : metabolic and endocrine aspects of adiposity

    NARCIS (Netherlands)

    van Dijk, G; de Vries, K; Benthem, L; Nyakas, C; Buwalda, B; Scheurink, AJW

    2003-01-01

    Abdominal obesity is a major risk factor to attract the insulin resistance syndrome. It is proposed that abdominal obesity exposes the liver to elevated levels of free fatty acids, which activate a neuroendocrine reflex, leading to increased circulating levels of glucocorticoids. Besides directly at

  15. Resistance training, insulin sensitivity and muscle function in the elderly

    DEFF Research Database (Denmark)

    Dela, Flemming; Kjaer, Michael

    2006-01-01

    Ageing is associated with a loss in both muscle mass and in the metabolic quality of skeletal muscle. This leads to sarcopenia and reduced daily function, as well as to an increased risk for development of insulin resistance and type 2 diabetes. A major part, but not all, of these changes...

  16. LMNA Mutations, Skeletal Muscle Lipid Metabolism, and Insulin Resistance

    OpenAIRE

    Boschmann, M.; Engeli, S; Moro, C.; A Luedtke; Adams, F.; Gorzelniak, K; G Rahn; A Mdhler; Dobberstein, K.; A Kr'ger; S. Schmidt; Spuler, S.; Luft, F. C.; Smith, S.R.; Schmidt, H. H.

    2010-01-01

    Context: Type 2 familial partial lipodystrophy (FPLD) is an autosomal-dominant lamin A/C-related disease associated with exercise intolerance, muscular pain, and insulin resistance. The symptoms may all be explained by defective metabolism; however, metabolism at the tissue level has not been investigated.

  17. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Tomoyuki [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Saotome, Masao, E-mail: msaotome@hama-med.ac.jp [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Funaki, Makoto [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Hayashi, Hideharu [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan)

    2014-05-01

    Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance

  18. Osteopontin is required for the early onset of high fat diet-induced insulin resistance in mice.

    Directory of Open Access Journals (Sweden)

    Justin Chapman

    Full Text Available BACKGROUND: Insulin resistance is manifested in muscle, adipose tissue, and liver and is associated with adipose tissue inflammation. The cellular components and mechanisms that regulate the onset of diet-induced insulin resistance are not clearly defined. METHODOLOGY AND PRINCIPAL FINDINGS: We initially observed osteopontin (OPN mRNA over-expression in adipose tissue of obese, insulin resistant humans and rats which was normalized by thiazolidinedione (TZD treatment in both species. OPN regulates inflammation and is implicated in pathogenic maladies resulting from chronic obesity. Thus, we tested the hypothesis that OPN is involved in the early development of insulin resistance using a 2-4 week high fat diet (HFD model. OPN KO mice fed HFD for 2 weeks were completely protected from the severe skeletal muscle, liver and adipose tissue insulin resistance that developed in wild type (WT controls, as determined by hyperinsulinemic euglycemic clamp and acute insulin-stimulation studies. Although two-week HFD did not alter body weight or plasma free fatty acids and cytokines in either strain, HFD-induced hyperleptinemia, increased adipose tissue inflammation (macrophages and cytokines, and adipocyte hypertrophy were significant in WT mice and blunted or absent in OPN KO mice. Adipose tissue OPN protein isoform expression was significantly altered in 2- and 4-week HFD-fed WT mice but total OPN protein was unchanged. OPN KO bone marrow stromal cells were more osteogenic and less adipogenic than WT cells in vitro. Interestingly, the two differentiation pathways were inversely affected by HFD in WT cells in vitro. CONCLUSIONS: The OPN KO phenotypes we report reflect protection from insulin resistance that is associated with changes in adipocyte biology and adipose tissue inflammatory status. OPN is a key component in the development of HFD-induced insulin resistance.

  19. Anaesthesia generates neuronal insulin resistance by inducing hypothermia

    Directory of Open Access Journals (Sweden)

    Sutherland Calum

    2008-10-01

    Full Text Available Abstract Background Anaesthesia is commonly employed prior to surgical investigations and to permit icv injections in rodents. Indeed it is standard practise in many studies examining the subsequent actions of hormones and growth factors on the brain. Recent evidence that the basal activity of specific intracellular signalling proteins can be affected by anaesthesia prompted us to examine the effect of anaesthesia not only on the basal activity but also the insulin sensitivity of the major insulin signalling pathways. Results We find that urethane- and ketamine-induced anaesthesia results in rapid activation of the phosphatidylinositol (PI 3-kinase-protein kinase B (PKB signalling pathway in the brain, increases tau phosphorylation while at the same time reducing basal activity of the Ras-ERK pathway. Subsequent injection of insulin does not alter the activity of either the PI 3-kinase or ERK signalling pathways, indicating a degree of neuronal molecular insulin resistance. However, if body temperature is maintained during anaesthesia then there is no alteration in the basal activity of these signalling molecules. Subsequent response of both pathways to insulin injection is restored. Conclusion The data is consistent with a hypothermia related alteration in neuronal signalling following anaesthesia, and emphasises the importance of maintaining the body temperature of rodents when monitoring insulin (or growth factor/neurotrophic agent action in the brain of anesthetised rodents.

  20. Are hypertriglyceridemia and low HDL causal factors in the development of insulin resistance?

    NARCIS (Netherlands)

    Li, Naishi; Fu, Jingyuan; Koonen, Debby P.; Kuivenhoven, Jan Albert; Snieder, Harold; Hofker, Marten H.

    2014-01-01

    Insulin resistance often occurs with dyslipidemia as part of the metabolic syndrome and the current dominant paradigm is that insulin resistance leads to dyslipidemia. However, dyslipidemia may also cause insulin resistance; this was postulated 30 years ago, but has never been substantiated. Establi

  1. Is myopia another clinical manifestation of insulin resistance?

    Science.gov (United States)

    Galvis, Virgilio; López-Jaramillo, Patricio; Tello, Alejandro; Castellanos-Castellanos, Yuly Andrea; Camacho, Paul Anthony; Cohen, Daniel Dylan; Gómez-Arbeláez, Diego; Merayo-Lloves, Jesús

    2016-05-01

    Myopia is a multifactorial visual refraction disease, in which the light rays from distant objects are focused in front of retina, causing blurry vision. Myopic eyes are characterized by an increased corneal curvature and/or ocular axial length. The prevalence of myopia has increased in recent decades, a trend that cannot be attributed exclusively to genetic factors. Low and middle income countries have a higher burden of refractive error, which we propose could be a consequence of a shorter exposure time to a westernized lifestyle, a phenomenon that may also explain the rapid increase in cardiometabolic diseases, such as diabetes, among those populations. We suggest that interactions between genetic, epigenetic and a rapidly changing environment are also involved in myopia onset and progression. Furthermore, we discuss several possible mechanisms by which insulin resistance may promote abnormal ocular growth and myopia to support the hypothesis that insulin resistance and hyperinsulinemia are involved in its pathogenesis, providing a link between trends in myopia and those of cardiometabolic diseases. There is evidence that insulin have direct ocular growth promoting effects as well an indirect effect via the induction of insulin-like growth factors leading to decreases insulin-like growth factor-binding protein, also implicated in ocular growth. PMID:27063082

  2. Intrinsic Frequency and the Single Wave Biopsy: Implications for Insulin Resistance.

    Science.gov (United States)

    Petrasek, Danny; Pahlevan, Niema M; Tavallali, Peyman; Rinderknecht, Derek G; Gharib, Morteza

    2015-11-01

    Insulin resistance is the hallmark of classical type II diabetes. In addition, insulin resistance plays a central role in metabolic syndrome, which astonishingly affects 1 out of 3 adults in North America. The insulin resistance state can precede the manifestation of diabetes and hypertension by years. Insulin resistance is correlated with a low-grade inflammatory condition, thought to be induced by obesity as well as other conditions. Currently, the methods to measure and monitor insulin resistance, such as the homeostatic model assessment and the euglycemic insulin clamp, can be impractical, expensive, and invasive. Abundant evidence exists that relates increased pulse pressure, pulse wave velocity (PWV), and vascular dysfunction with insulin resistance. We introduce a potential method of assessing insulin resistance that relies on a novel signal-processing algorithm, the intrinsic frequency method (IFM). The method requires a single pulse pressure wave, thus the term " wave biopsy." PMID:26183600

  3. Insulin as the main regulator of cellular glucose utilization--aetiological aspects of insulin resistance.

    Science.gov (United States)

    Tatoń, Jan; Czech, Anna; Piatkiewicz, Paweł

    2010-01-01

    This review presents the advances in the molecular biology and the pathophysiology of insulin resistance with emphasis on disturbances in cellular glucose transport. New scientific information about the structure and function of glucotransporters from the GLUT4 and SLGT families underline their significance in endocrinopathies and metabolic disease pathogenesis as related to insulin resistance. The new discoveries in this area also contribute to a better understanding of the regulation of insulin receptor and post-receptor reactivity by hormones and by drugs. They refer to the regulation of glycaemia and to its disturbances in diabetes mellitus, particularly of type 2, to metabolic syndrome, and, in general, to the pathogenesis of many syndromes and clinical disturbances caused by insulin resistance. Impairment of cellular glucose transport may be one of the primary aetiological factors in this respect. Therefore, studies of cellular glucotransporters expression and function promise new clinical and pharmacotherapeutic developments. Progress in this area has already been transformed into many practical proposals which are improving clinical practice. PMID:20806184

  4. Molecular Mechanism of Insulin Resistance in Obesity and Type 2 Diabetes

    OpenAIRE

    Choi, Kangduk; Kim, Young-Bum

    2010-01-01

    Insulin resistance is a major risk factor for developing type 2 diabetes caused by the inability of insulin-target tissues to respond properly to insulin, and contributes to the morbidity of obesity. Insulin action involves a series of signaling cascades initiated by insulin binding to its receptor, eliciting receptor autophosphorylation and activation of the receptor tyrosine kinase, resulting in tyrosine phosphorylation of insulin receptor substrates (IRSs). Phosphorylation of IRSs leads to...

  5. Recent Advances in Obesity-induced Inflammation and Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Sanshiro eTateya

    2013-08-01

    Full Text Available It has been demonstrated in rodents and humans that chronic inflammation characterized by macrophage infiltration occurs mainly in adipose tissue or liver during obesity, in which activation of immune cells is closely associated with insulin sensitivity. Macrophages can be classified as classically activated (M1 macrophages that support microbicidal activity or alternatively activated (M2 macrophages that support allergic and antiparasitic responses. In the context of insulin action, M2 macrophages sustain insulin sensitivity by secreting IL-4 and IL-10, while M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines, such as TNFα. Polarization of M1/M2 is controlled by various dynamic functions of other immune cells. It has been demonstrated that, in a lean state, TH2 cells, Treg cells, natural killer T cells, or eosinophils contribute to the M2 activation of macrophages by secreting IL-4 or IL10. In contrast, obesity causes alteration of the constituent immune cells, in which TH1 cells, B cells, neutrophils, or mast cells induce M1 activation of macrophages by the elevated secretion of TNFα and IFNγ. Increased secretion of TNFα and free fatty acids from hypertrophied adipocytes also contributes to the M1 activation of macrophages. Since obesity-induced insulin resistance is established by macrophage infiltration and the activation of immune cells inside tissues, identification of the factors that regulate accumulation and the intracellular signaling cascades that define polarization of M1/M2 would be indispensable. Regulation of these factors would lead to the pharmacological inhibition of obesity-induced insulin resistance. In this review, we introduce molecular mechanisms relevant to the pathophysiology and review the most recent studies of clinical applications targeting chronic inflammation.

  6. Recent advances in obesity-induced inflammation and insulin resistance.

    Science.gov (United States)

    Tateya, Sanshiro; Kim, Francis; Tamori, Yoshikazu

    2013-01-01

    It has been demonstrated in rodents and humans that chronic inflammation characterized by macrophage infiltration occurs mainly in adipose tissue or liver during obesity, in which activation of immune cells is closely associated with insulin sensitivity. Macrophages can be classified as classically activated (M1) macrophages that support microbicidal activity or alternatively activated (M2) macrophages that support allergic and antiparasitic responses. In the context of insulin action, M2 macrophages sustain insulin sensitivity by secreting IL-4 and IL-10, while M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines, such as TNFα. Polarization of M1/M2 is controlled by various dynamic functions of other immune cells. It has been demonstrated that, in a lean state, TH2 cells, Treg cells, natural killer T cells, or eosinophils contribute to the M2 activation of macrophages by secreting IL-4 or IL-10. In contrast, obesity causes alteration of the constituent immune cells, in which TH1 cells, B cells, neutrophils, or mast cells induce M1 activation of macrophages by the elevated secretion of TNFα and IFNγ. Increased secretion of TNFα and free fatty acids from hypertrophied adipocytes also contributes to the M1 activation of macrophages. Since obesity-induced insulin resistance is established by macrophage infiltration and the activation of immune cells inside tissues, identification of the factors that regulate accumulation and the intracellular signaling cascades that define polarization of M1/M2 would be indispensable. Regulation of these factors would lead to the pharmacological inhibition of obesity-induced insulin resistance. In this review, we introduce molecular mechanisms relevant to the pathophysiology and review the most recent studies of clinical applications targeting chronic inflammation. PMID:23964268

  7. Association of fasting glucagon and proinsulin concentrations with insulin resistance

    DEFF Research Database (Denmark)

    Ferrannini, E; Muscelli, E; Natali, A;

    2007-01-01

    AIMS/HYPOTHESIS: Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non-diabetic individuals. METHODS: We measured IR [by a euglycaemic......, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin...

  8. Development of Wistar rat model of insulin resistance

    Institute of Scientific and Technical Information of China (English)

    Jing Ai; Ning Wang; Mei Yang; Zhi-Min Du; Yong-Chun Zhang; Bao-Feng Yang

    2005-01-01

    AIM: To establish a simplified and reliable animal model of insulin resistance with low cost in Wistar rats. METHODS: Wistar rats were treated with a high fat emulsion by ig for 10 d. Changes of the diets, drinking and body weight were monitored every day and insulin resistance was evaluated by hyperinsulinemic-euglycemicclamp techniques and short insulin tolerance test using capillary blood glucose. Morphologic changes of liver, fat, skeletal muscles, and pancreatic islets were assessed under light microscope. mRNA expressions of GLUT2 and α-glucosidase in small intestine epithelium, GLUT4 in skeletal muscles and Kir6.2 in beta cell of islets were determined by in situ hybridization.RESULTS: KITT was smaller in treated animals (4.5±0.9)than in untreated control Wistar rats (6.8±1.5), and so was glucose injection rate. Both adipocyte hypertrophy and large pancreatic islets were seen in high fat fed rats,but no changes of skeletal muscles and livers wereobserved. mRNA levels of GLUT2, α-glucosidase in small intestinal epithelium and Kir6.2 mRNA in beta cells of islets increased, whereas that of GLUT4 in skeletal muscles decreased in high fat fed group compared with normal control group.CONCLUSION: An insulin resistance animal model in Wistar rats is established by ig special fat emulsion.

  9. Influence of Gut Microbiota on Subclinical Inflammation and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Bruno Melo Carvalho

    2013-01-01

    Full Text Available Obesity is the main condition that is correlated with the appearance of insulin resistance, which is the major link among its comorbidities, such as type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. Obesity affects a large number of individuals worldwide; it degrades human health and quality of life. Here, we review the role of the gut microbiota in the pathophysiology of obesity and type 2 diabetes, which is promoted by a bacterial diversity shift mediated by overnutrition. Whole bacteria, their products, and metabolites undergo increased translocation through the gut epithelium to the circulation due to degraded tight junctions and the consequent increase in intestinal permeability that culminates in inflammation and insulin resistance. Several strategies focusing on modulation of the gut microbiota (antibiotics, probiotics, and prebiotics are being experimentally employed in metabolic derangement in order to reduce intestinal permeability, increase the production of short chain fatty acids and anorectic gut hormones, and promote insulin sensitivity to counteract the inflammatory status and insulin resistance found in obese individuals.

  10. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications.

  11. Proinsulin and insulin profile in acute myocardial infarction

    International Nuclear Information System (INIS)

    Proinsulin and insulin in 104 and glucagon in 10 cases were estimated by radioimmunoassay (RIA) technique in uncomplicated cases of acute myocardial infarction (A.M.I.), matched against 44 and 5 controls respectively. Patients were divided into group A and B based on oral glucose tolerance test (G.T.T.) done on the following morning after admission. Group A comprised of 65 and group B comprised of 49 patients with normal and abnormal G.T.T. respectively. The tests were repeated prior to discharge from the hospital at the end of 6th week. The initial values of insulin and glucagon were found to be significantly raised in both the groups but came down to normal in group A whereas they remained unchanged in group B in the follow up study. Proinsulin values in group A were not significantly changed both in initial and follow up study. In group B proinsulin values were found to be significantly low both initially and in the follow up study. G.T.T. in group B remained abnormal even at the end of the 6th week. (author)

  12. Proinsulin and insulin profile in acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Mowar, S.N.; Pal, S.K.; Chhetri, M.K.; Ghosh, K.K. (Institute of Post-Graduate Medical Education and Research, Calcutta (India))

    Proinsulin and insulin in 104 and glucagon in 10 cases were estimated by radioimmunoassay (RIA) technique in uncomplicated cases of acute myocardial infarction (A.M.I.), matched against 44 and 5 controls respectively. Patients were divided into group A and B based on oral glucose tolerance test (G.T.T.) done on the following morning after admission. Group A comprised of 65 and group B comprised of 49 patients with normal and abnormal G.T.T. respectively. The tests were repeated prior to discharge from the hospital at the end of 6th week. The initial values of insulin and glucagon were found to be significantly raised in both the groups but came down to normal in group A whereas they remained unchanged in group B in the follow up study. Proinsulin values in group A were not significantly changed both in initial and follow up study. In group B proinsulin values were found to be significantly low both initially and in the follow up study. G.T.T. in group B remained abnormal even at the end of the 6th week.

  13. Insulin resistance in different forms of hyperketonemia and in cows affected by puerperal metritis

    International Nuclear Information System (INIS)

    In dairy cows selected for high milk production the phenomenon of insulin resistance (IR) seems to play a pivotal role both in adaptation to the postpartum negative energy balance and in the aetiology of some periparturient metabolic disturbances. Perturbation of pancreatic insulin secretion and insulin sensitivity of peripheral tissues has been documented in the pathogenesis of abomasal displacement, cystic ovarian disease, excessive lipid accumulation in the liver and ketosis. In human population and in laboratory animal models pro-inflammatory cytokines like tumour necrosis factor-alpha (TNF-α) play an essential role in the development of IR that occurs in association with obesity, acute infections and endotoxaemia. A similar interaction between the intensive release of pro-inflammatory cytokines and IR has been recently explored also in ruminants. This trial was conducted in high-yielding dairy cows challenged with standard intravenous doses of glucose and insulin in different time intervals to parturition. The aim was to determine the grade and time-related changes of (i) glucose-stimulated insulin increase and (ii) insulin-induced glucose decline, furthermore (iii) the interrelation of these challenge tests with plasma levels of metabolites and metabolic hormones in cows showing various ketone pattern with and without puerperal metritis. 28 multiparous Holstein cows (previous 305 FCM day milk: 8331±192.8 L) were subjected to intravenous glucose tolerance test (IVGTT) on day -18, 7 and 70 around calving. Plasma βOH butyrate (BHB), non-esterified fatty acid (NEFA), glucose, insulin, insulin-like growth factor I (IGF-I) and leptin levels were measured regularly from -18 d before, till d 70 after calving. Cows were milked out twice a day. The course of postpartum uterine involution was checked regularly, and cows showing clinical signs of bacterial complications were treated with antibiotics combined with repeated administration of PGF2α. All cows showing

  14. Oxidative stress, insulin resistance, dyslipidemia and type 2diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Surapon Tangvarasittichai

    2015-01-01

    Oxidative stress is increased in metabolic syndromeand type 2 diabetes mellitus (T2DM) and this appearsto underlie the development of cardiovascular disease,T2DM and diabetic complications. Increased oxidativestress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM.

  15. Age-related inflammation and insulin resistance: a review of their intricate interdependency

    OpenAIRE

    Park, Min Hi; Kim, Dae Hyun; Lee, Eun Kyeong; Kim, Nam Deuk; Im, Dong Soon; Lee, Jaewon; Yu, Byung Pal; Chung, Hae Young

    2014-01-01

    Chronic inflammation is a major risk factor underlying aging and the associated diseases of aging; of particular interest is insulin resistance during aging. Chronic inflammation impairs normal lipid accumulation, adipose tissue function, mitochondrial function, and causes endoplasmic reticulum (ER) stress, which lead to insulin resistance. However, some studies show that insulin resistance itself amplifies chronic inflammation. The activity of the insulin-dependent Akt signaling pathway is h...

  16. Glucose and lipid metabolism in insulin resistance : an experimental study in fat cells

    OpenAIRE

    Burén, Jonas

    2003-01-01

    Type 2 diabetes is usually caused by a combination of pancreatic β-cell failure and insulin resistance in target tissues like liver, muscle and fat. Insulin resistance is characterised by an impaired effect of insulin to reduce hepatic glucose production and to promote glucose uptake in peripheral tissues. The focus of this study was to further elucidate cellular mechanisms for insulin resistance that may be of relevance for type 2 diabetes in humans. We used rat and human adipocytes as an es...

  17. The Role of Hepatic FoxO1 in Insulin Resistance

    OpenAIRE

    Ling, Alisha Viva

    2015-01-01

    Metabolic syndrome is a major health concern in the US, affecting a third of all adults and amplifying the risk of cardiovascular disease and diabetes. The central pathophysiological root of metabolic syndrome is widely considered to be insulin resistance, though the mechanisms linking insulin resistance to this clinical constellation of obesity, dyslipidemia, hypertension and hepatic steatosis are poorly understood. In insulin resistance, insulin suppression of the forkhead box protein O1 (F...

  18. Status of serum adiponectin related to insulin resistance in prediabetics

    International Nuclear Information System (INIS)

    Obejctive: To find the status of serum adiponectin in individuals progressing towards Type 2 diabetes mellitus and compare it with normal glucose tolerant subjects to determine the stage where alteration of adiponectin occurred. Methods: The cross-sectional study was carried out at the Department of Biochemistry, Jinnah Postgraduate Medical Centre, Karachi, during January to August 2008. Subjects were invited through various diabetes screening camps. A total of 608 subjects >30 years of age without prior history of diabetes were screened through fasting plasma glucose and 2-hour oral glucose tolerance test. Forty randomly selected pre-diabetic subjects and 40 age and gender-matched subjects were included in the study. Anthropometric measurements were done. Serum insulin and adiponectin were estimated by enzyme-linked immunosorbent assay. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance mathematically. Result: Mean fasting and two-hour plasma glucose, body mass index, waist, hip circumference and blood pressure were significantly raised in pre-diabetics compared to those with normal glucose tolerance. Adiponectin was significantly decreased, while insulin and HOMA-IR were raised significantly in the pre-diabetics. Adiponectin showed significant negative correlation with body mass index (r=-0.31, p=0.005), fasting plasma glucose (r=-0.24, p= 0.032), 2-hour plasma glucose (r=-0.42, p<0.0001)), insulin (r-0.43, p<0.0001) and HOMA-IR (r= -0.43, p<0.0001) and remained significant after adjustment of body mass index, gender and insulin level in pre-diabetics. Conclusion: Adiponectin estimation may help in earlier identification of impending diabetes. However, casual link between adiponectin and pre-diabetes remained unexplored due to the study design and small sample size that warrants longitudinal large-scale studies. (author)

  19. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

    DEFF Research Database (Denmark)

    Bouzakri, Karim; Plomgaard, Peter; Berney, Thierry;

    2011-01-01

    Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) ß-cells....

  20. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

    DEFF Research Database (Denmark)

    Bouzakri, Karim; Plomgaard, Peter; Berney, Thierry;

    2011-01-01

    Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells....

  1. Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Rattigan, Stephen; Jeppesen, Jacob Fuglsbjerg;

    2015-01-01

    this could be reversed by GLP-1. Using contrast-enhanced ultrasound, microvascular recruitment was assessed by continuous real-time imaging of gas-filled microbubbles in the microcirculation after acute (5 days) and prolonged (8 weeks) high fat diet (HF) induced insulin resistance in rats. An euglycemic......-mediated glucose uptake compared to controls. Acute administration of GLP-1 restored normal microvascular response by increasing the MVR after both 5 days and 8 weeks HF intervention (Pbody insulin sensitivity and increased insulin...

  2. Insulin

    Science.gov (United States)

    ... Short Acting Humulin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Novolin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Lantus Insulin Glargine Long Acting ...

  3. 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 patients with syndromes of extreme insulin resistance....

  4. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes.

    Science.gov (United States)

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J; Blaszczak, Alecia; Kashyap, Sangeeta R; Kirwan, John P

    2013-11-15

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training. PMID:24064339

  5. Lifecourse Childhood Adiposity Trajectories Associated With Adolescent Insulin Resistance

    OpenAIRE

    Huang, Rae-Chi; de Klerk, Nicholas H.; Smith, Anne; Kendall, Garth E; Landau, Louis I.; Mori, Trevor A; NEWNHAM, John P; Stanley, Fiona J; Oddy, Wendy H; Hands, Beth; Lawrence J. Beilin

    2011-01-01

    OBJECTIVE In light of the obesity epidemic, we aimed to characterize novel childhood adiposity trajectories from birth to age 14 years and to determine their relation to adolescent insulin resistance. RESEARCH DESIGN AND METHODS A total of 1,197 Australian children with cardiovascular/metabolic profiling at age 14 years were studied serially from birth to age 14 years. Semiparametric mixture modeling was applied to anthropometric data over eight time points to generate adiposity trajectories ...

  6. Hyperandrogenism-Insulin Resistance-Acanthosis Nigricans Syndrome

    OpenAIRE

    Dédjan, A. H.; A. Chadli; El Aziz, S.; Farouqi, A.

    2015-01-01

    Introduction. Female hyperandrogenism is a frequent motive of consultation. It is revealed by hirsutism, acne or seborrhea, and disorders in menstruation cycle combined or not with virilisation signs. Several etiologies are incriminated but the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome is rare. Observation. A 20-year-old girl, having had a five-year-old secondary amenorrhea. The exam revealed a patient, normotensive with a body mass index at 30 kg/m2 and a waist measur...

  7. Relationship between insulin resistance and plasma vitamin D in adults

    Directory of Open Access Journals (Sweden)

    Badawi A

    2014-07-01

    Full Text Available Alaa Badawi,1 Suzan Sayegh,2 Eman Sadoun,3 Mohamed Al-Thani,2 Paul Arora,4 Pierre S Haddad51Office of Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, ON, Canada; 2Department of Public Health, 3Clinical Research Division, Supreme Council of Health, Doha, Qatar; 4Dalla Lana School of Public Health, University of Toronto, ON, Canada; 5Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, QC, CanadaAbstract: A recent relationship between vitamin D deficiency and the risk of type 2 diabetes mellitus (T2DM and insulin resistance has been established through several studies. Research suggests a correlation between serum vitamin D and glycemic status measures. The aim of this study was to investigate the relationship between the plasma vitamin D levels (25[OH]D and the factors linked to insulin resistance in a representative sample of Canadians ranging in age from 16–79 years. Data were used from the Canadian Health Measures Survey where direct measures of health and wellness were reported from 1,928 subjects. These data were gathered from March 2007–February 2009 at 15 sites selected through a multistage sampling strategy. An inverse relationship between insulin resistance and plasma vitamin D level in both men and women was observed. This study provides additional evidence for the role of vitamin D in T2DM. If causally associated, the supplementation of vitamin D may help in preventing insulin resistance and subsequent T2DM.Keywords: HOMA-IR, plasma 25(OHD, diabetes

  8. Insulin resistance of muscle protein metabolism in aging

    OpenAIRE

    Rasmussen, Blake B.; Fujita, Satoshi; Wolfe, Robert R.; Mittendorfer, Bettina; Roy, Mona; Rowe, Vincent L.; Volpi, Elena

    2006-01-01

    A reduced response of older skeletal muscle to anabolic stimuli may contribute to the development of sarcopenia. We hypothesized that muscle proteins are resistant to the anabolic action of insulin in the elderly. We examined the effects of hyperinsulinemia on muscle protein metabolism in young (25±2 year) and older (68±1 year) healthy subjects using stable isotope tracer techniques. Leg blood flow was higher in the young at baseline and increased during hyperinsulinemia, whereas it did not c...

  9. Influence of Gut Microbiota on Subclinical Inflammation and Insulin Resistance

    OpenAIRE

    Bruno de Melo Carvalho; Mario Jose Abdalla Saad

    2013-01-01

    Obesity is the main condition that is correlated with the appearance of insulin resistance, which is the major link among its comorbidities, such as type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. Obesity affects a large number of individuals worldwide; it degrades human health and quality of life. Here, we review the role of the gut microbiota in the pathophysiology of obesity and type 2 diabetes, which is promote...

  10. Sildenafil Reduces Insulin-Resistance in Human Endothelial Cells

    OpenAIRE

    Caterina Mammi; Donatella Pastore; Lombardo, Marco F; Francesca Ferrelli; Massimiliano Caprio; Claudia Consoli; Manfredi Tesauro; Lucia Gatta; Massimo Fini; Massimo Federici; Paolo Sbraccia; Giulia Donadel; Alfonso Bellia; Giuseppe M Rosano; Andrea Fabbri

    2011-01-01

    BACKGROUND: The efficacy of Phosphodiesterase 5 (PDE5) inhibitors to re-establish endothelial function is reduced in diabetic patients. Recent evidences suggest that therapy with PDE5 inhibitors, i.e. sildenafil, may increase the expression of nitric oxide synthase (NOS) proteins in the heart and cardiomyocytes. In this study we analyzed the effect of sildenafil on endothelial cells in insulin resistance conditions in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Human umbilical vein endothelial cel...

  11. Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study

    Directory of Open Access Journals (Sweden)

    Isao Saito

    2015-09-01

    Full Text Available Background: Although impaired cardiac autonomic function is associated with an increased risk of type 2 diabetes in Caucasians, evidence in Asian populations with a lower body mass index is limited. Methods: Between 2009–2012, the Toon Health Study recruited 1899 individuals aged 30–79 years who were not taking medication for diabetes. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes, and fasting and 2-h-postload glucose and insulin concentrations were measured. We assessed the homeostasis model assessment index for insulin resistance (HOMA-IR and Gutt’s insulin sensitivity index (ISI. Pulse was recorded for 5 min, and time-domain heart rate variability (HRV indices were calculated: the standard deviation of normal-to-normal intervals (SDNN and the root mean square of successive difference (RMSSD. Power spectral analysis provided frequency domain measures of HRV: high frequency (HF power, low frequency (LF power, and the LF:HF ratio. Results: Multivariate-adjusted logistic regression models showed decreased SDNN, RMSSD, and HF, and increased LF:HF ratio were associated significantly with increased HOMA-IR and decreased ISI. When stratified by overweight status, the association of RMSSD, HF, and LF:HF ratio with decreased ISI was also apparent in non-overweight individuals. The interaction between LF:HF ratio and decreased ISI in overweight individuals was significant, with the odds ratio for decreased ISI in the highest quartile of LF:HF ratio in non-overweight individuals being 2.09 (95% confidence interval, 1.41–3.10. Conclusions: Reduced HRV was associated with insulin resistance and lower insulin sensitivity. Decreased ISI was linked with parasympathetic dysfunction, primarily in non-overweight individuals.

  12. Increased interaction with insulin receptor substrate 1, a novel abnormality in insulin resistance and type 2 diabetes

    DEFF Research Database (Denmark)

    Caruso, Michael; Ma, Danjun; Msallaty, Zaher;

    2014-01-01

    Insulin receptor substrate 1 (IRS1) is a key mediator of insulin signal transduction. Perturbations involving IRS1 complexes may lead to the development of insulin resistance and type 2 diabetes (T2D). Surprisingly little is known about the proteins that interact with IRS1 in humans under health...... and disease conditions. We used a proteomic approach to assess IRS1 interaction partners in skeletal muscle from lean healthy control subjects (LCs), obese insulin-resistant nondiabetic control subjects (OCs), and participants with T2D before and after insulin infusion. We identified 113 novel endogenous IRS1...... of proteins in OCs and/or T2D patients exhibited increased associations with IRS1 compared with LCs under the basal and/or insulin-stimulated conditions, revealing multiple new dysfunctional IRS1 pathways in OCs and T2D patients. This novel abnormality, increased interaction of multiple proteins with IRS1...

  13. The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance

    OpenAIRE

    Yun Zhao; Zhuqi Tang; Aiguo Shen; Tao Tao; Chunhua Wan; Xiaohui Zhu; Jieru Huang; Wanlu Zhang; Nana Xia; Suxin Wang; Shiwei Cui; Dongmei Zhang

    2015-01-01

    Protein tyrosine phosphatase 1B (PTP1B), which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1), thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several important components of insulin signal pathway. In this study, we identified that PTP1B is modified by O-GlcNAcylation at three O-GlcNAc sites (Ser104, Ser201...

  14. Physical exercise and pancreatic islets: acute and chronic actions on insulin secretion.

    Science.gov (United States)

    Almeida, Felipe N; Proença, André R G; Chimin, Patrícia; Marçal, Anderson C; Bessa-Lima, Fábio; Carvalho, Carla R O

    2012-01-01

    Diabetes mellitus (DM) is a great public health problem, which attacks part of the world population, being characterized by an imbalance in body glucose homeostasis. Physical exercise is pointed as a protective agent and is also recommended to people with DM. As pancreatic islets present an important role in glucose homeostasis, we aim to study the role of physical exercise (chronic adaptations and acute responses) in pancreatic islets functionality in Wistar male rats. First, animals were divided into two groups: sedentary (S) and aerobic trained (T). At the end of 8 weeks, half of them (S and T) were submitted to an acute exercise session (exercise until exhaustion), being subdivided as acute sedentary (AS) and acute trained (AT). After the experimental period, periepididymal, retroperitoneal and subcutaneous fat pads, blood, soleus muscle and pancreatic islets were collected and prepared for further analysis. From the pancreatic islets, total insulin content, insulin secretion stimulated by glucose, leucine, arginine and carbachol were analyzed. Our results pointed that body adiposity and glucose homeostasis improved with chronic physical exercise. In addition, total insulin content was reduced in group AT, insulin secretion stimulated by glucose was reduced in trained groups (T and AT) and insulin secretion stimulated by carbachol was increased in group AT. There were no significant differences in insulin secretion stimulated by arginine and leucine. We identified a possible modulating action on insulin secretion, probably related to the association of chronic adaptation with an acute response on cholinergic activity in pancreatic islets. PMID:22868676

  15. HOMA-ESTIMATED INSULIN RESISTANCE IN NONDIABETIC INDIVIDUALS

    Institute of Scientific and Technical Information of China (English)

    任颖; 刘伟; 黄钢; 黄定九; 陆广华; 李惠娟; 季正明; 郁小英

    2004-01-01

    Objective To assess the relationship between HOMA-estimated insulin resistance and risk factors of cardiovascular disease in the general population. Methods 268 eligible subjects of Pudong ShangGan community, aged 45 ~ 80 years, volunteered to participate in this cross-sectional survey. Fasting insulin was measured by means of a radioimmunoassay. Results Anthropometric parameters,fasting blood glucose and insulin,increased in a linear fashion across quartiles of HOMA-IR after adjustment for age and sex. HOMA-IR was significantly associated with measures of anthropometry ( BMI,r = 0. 30;waist circumference, r =0. 35; and waist-to-hip ratio, r =0. 21 ), fasting ( glucose, r = 0. 41; insulin, r = 0. 71 ), and cardiovascular risk factors ( cholesterol, r =0. 23; triglyceride, r = 0. 31; systolic blood pressure, r = 0. 25; and diastolic blood pressure, r = 0. 20; all P <0. 0001 ). In logistic regression analysis, odds ratios indicate that individuals with obesity ( high levels of BMI and waist circumference) were more than 4 times likely to have elevated HOMA-IR. With increase of log triglycerides,the risk of having elevated HOMA-IR increased more than 2.4 times. For increase in systolic and diastolic blood pressure, the likelihood of having elevated HOMA-IR increased >1.8 times. Conclusion HOMA-IR was significantly and independently associated with risk factors of cardiovascular disease in this study.

  16. The Role of Gut Microbiota on Insulin Resistance

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    Mario J. A. Saad

    2013-03-01

    Full Text Available The development of obesity and insulin resistance has been extensively studied in the last decades, but the mechanisms underlying these alterations are still not completely understood. The gut microbiota has been identified as a potential contributor to metabolic diseases. It has been shown that obese individuals present different proportions of bacterial phyla compared with lean individuals, with an increase in Firmicutes and Actinobacteria and a decrease in Bacteroidetes. This alteration seems to interfere with intestinal permeability, increasing the absorption of lipopolysaccharide (LPS, which reaches circulation and initiates activation of Toll-like receptor (TLR 4 and 2 and LPS receptor CD14, leading to increased activation of inflammatory pathways. With these activations, an impairment of the insulin signaling is observed, with decreased phosphorylation of the insulin receptor, insulin receptor substrate (IRS and Akt, as well as increased inhibitory serine phosphorylation of IRS-1. Altered proportions of bacterial phyla have also been demonstrated to interfere with host’s biochemical pathways, increasing energy extraction and depot in adipose tissue. Therefore, understanding the mechanisms by which the alteration in the gut microbiota produces different signaling activations and phenotype changes may offer an interesting opportunity for the treatment of obesity and type 2 diabetes.

  17. A common variation of the PTEN gene is associated with peripheral insulin resistance

    DEFF Research Database (Denmark)

    Grinder-Hansen, L; Ribel-Madsen, R; Wojtaszewski, Jørgen;

    2016-01-01

    ). Hepatic and peripheral insulin sensitivity was measured using tracer and euglycaemic-hyperinsulinaemic clamp techniques; insulin secretion was assessed by intravenous glucose tolerance test; and muscle biopsies were taken during insulin infusion from 150 twins for measurement of PI3K and Akt activities....... RESULTS: The minor G allele of PTEN rs11202614 was associated with elevated fasting plasma insulin levels and a decreased peripheral glucose disposal rate, but not with the hepatic insulin resistance index or insulin secretion measured as the first-phase insulin response and disposition index. The single...

  18. Mitochondrial involvement in skeletal muscle insulin resistance: A case of imbalanced bioenergetics.

    Science.gov (United States)

    Affourtit, Charles

    2016-10-01

    Skeletal muscle insulin resistance in obesity associates with mitochondrial dysfunction, but the causality of this association is controversial. This review evaluates mitochondrial models of nutrient-induced muscle insulin resistance. It transpires that all models predict that insulin resistance arises as a result of imbalanced cellular bioenergetics. The nature and precise origin of the proposed insulin-numbing molecules differ between models but all species only accumulate when metabolic fuel supply outweighs energy demand. This observation suggests that mitochondrial deficiency in muscle insulin resistance is not merely owing to intrinsic functional defects, but could instead be an adaptation to nutrient-induced changes in energy expenditure. Such adaptive effects are likely because muscle ATP supply is fully driven by energy demand. This market-economic control of myocellular bioenergetics offers a mechanism by which insulin-signalling deficiency can cause apparent mitochondrial dysfunction, as insulin resistance lowers skeletal muscle anabolism and thus dampens ATP demand and, consequently, oxidative ATP synthesis. PMID:27473535

  19. Beneficial Effects of Ethanol Consumption on Insulin Resistance Are Only Applicable to Subjects Without Obesity or Insulin Resistance; Drinking is not Necessarily a Remedy for Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Hirokazu Yokoyama

    2011-07-01

    Full Text Available Although moderate drinking has been shown to lower insulin resistance levels, it is still unclear whether alcoholic beverages could be remedies for insulin resistance. To elucidate this, the correlation between levels of ethanol consumption and insulin resistance were cross-sectionally examined in 371 non-diabetic male Japanese workers. Multiple regression analysis demonstrated that the ethanol consumption level was inversely correlated with the insulin resistance level assessed by homeostatic model assessment (HOMA-IR, p = 0.0014, the serum insulin level (p = 0.0007, and pancreatic β-cell function, also assessed by HOMA (HOMA-β, p = 0.0002, independently from age, body mass index (BMI, and blood pressure, liver function tests, and lipid profiles status, as well as serum adiponectin. The correlations were true in subjects with normal BMIs (up to 25.0 kg/m2, n = 301 or normal HOMA-IR (up to 2.0 µIU·mg/µL·dL n = 337, whereas all of them were non-significant in those with excessive BMIs (n = 70 or in those with HOMA-IR of more than 2.0 (n = 34. Although it is still unclear whether the reductions of these parameters by ethanol consumption are truly due to the improvement of insulin resistance, at least, these effects are not applicable to subjects with obesity and/or insulin resistance. Thus, alcoholic beverages could not be remedies for insulin resistance or metabolic syndrome.

  20. [Simvastatin's effect on insulin resistance in rats with diabetes mellitus].

    Science.gov (United States)

    Iskakova, S; Zharmakhanova, G; Bekmukhambetov, Y; Dworacka, M; Dworacki, G

    2015-05-01

    The aim of this experimental study was to estimate the effect of Simvastatin on glycemic variability-related insulin resistance in the course of diabetes mellitus (DM) in rats. Fifty seven male Wistar rats were divided into four groups: I - rats with diabetes mellitus and glycemic variability treated with Simvastatin (20 mg/kg body weight, intragastral during 8 weeks); II - placebo-treated rats with DM and glycemic variability; III - placebo treated rats with DM and IV - nondiabetic control rats. DM was induced by feeding rats with high-fat diet (61%) during five weeks and low-dose of Streptozotocin (30 mg/kg, intraperitoneally). Daily glucose excursions were stimulated by feeding animals twice a day. We measured fasting blood glucose, glycated hemoglobin (HbA1c), insulin and HOMAIR was calculated. Higher insulin resistance in diabetic rats is related to greater daily glycemic variability. In our study was installed significant increasing HOMAIR in diabetics rats with glycemic excursions comparison with the control. Our results showed that the simvastatin-treatment decreases the indices glycemic variability and HOMA in diabetic rats with glycemic excursions.

  1. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.

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    Pernilla Lång

    Full Text Available BACKGROUND: Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer. PRINCIPAL FINDINGS: Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity. CONCLUSION: Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

  2. Role of oxidative stress in endothelial insulin resistance

    Institute of Scientific and Technical Information of China (English)

    Francesco Paneni; Sarah Costantino; Francesco Cosentino

    2015-01-01

    The International Diabetes Federation estimates that 316 million people are currently affected by impaired glucose tolerance (IGT). Most importantly, recent forecasts anticipate a dramatic IGT increase with more that 470 million people affected by the year 2035. Impaired insulin sensitivity is major feature of obesity and diabetes and is strongly linked with adverse cardiometabolic phenotypes. However, the etiologic pathway linking impaired glucose tolerance and cardiovascular disease remains to be deciphered. Although insulin resistance has been attributed to inflammatory programs starting in adipose tissue, emerging evidence indicates thatendothelial dysfunction may represent the upstreamevent preceding peripheral impairment of insulinsensitivity. Indeed, suppression of reactive oxygenspecies-dependent pathways in the endothelium hasshown to restore insulin delivery to peripheral organsby preserving nitric oxide (NO) availability. Here wedescribe emerging theories concerning endothelialinsulin resistance, with particular emphasis on the roleoxidative stress. Complex molecular circuits includingendothelial nitric oxide synthase, prostacyclin synthase,mitochondrial adaptor p66Shc, nicotinamide adeninedinucleotide phosphate-oxidase oxidase and nuclearfactor kappa-B are discussed. Moreover, the reviewprovides insights on the effectiveness of availablecompounds (i.e. , ruboxistaurin, sildenafil, endothelinreceptor antagonists, NO donors) in restoring endothelialinsulin signalling. Taken together, these aspects maysignificantly contribute to design novel therapeuticapproaches to restore glucose homeostasis in patientswith obesity and diabetes.

  3. Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

    Science.gov (United States)

    Hinton, Pamela S

    2016-08-01

    Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

  4. Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity.

    OpenAIRE

    Caro, J F; Ittoop, O; Pories, W J; Meelheim, D; Flickinger, E G; Thomas, F; Jenquin, M; Silverman, J F; Khazanie, P G; Sinha, M. K.

    1986-01-01

    We have developed a method to isolate insulin-responsive human hepatocytes from an intraoperative liver biopsy to study insulin action and resistance in man. Hepatocytes from obese patients with noninsulin-dependent diabetes were resistant to maximal insulin concentration, and those from obese controls to submaximal insulin concentration in comparison to nonobese controls. Insulin binding per cell number was similar in all groups. However, insulin binding per surface area was decreased in the...

  5. Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; ter Wee, PM; Gans, ROB

    1999-01-01

    Background. Insulin induces increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects coul

  6. A novel insulin receptor-signaling platform and its link to insulin resistance and type 2 diabetes.

    Science.gov (United States)

    Alghamdi, Farah; Guo, Merry; Abdulkhalek, Samar; Crawford, Nicola; Amith, Schammim Ray; Szewczuk, Myron R

    2014-06-01

    Insulin-induced insulin receptor (IR) tyrosine kinase activation and insulin cell survival responses have been reported to be under the regulation of a membrane associated mammalian neuraminidase-1 (Neu1). The molecular mechanism(s) behind this process is unknown. Here, we uncover a novel Neu1 and matrix metalloproteinase-9 (MMP-9) cross-talk in alliance with neuromedin B G-protein coupled receptor (GPCR), which is essential for insulin-induced IR activation and cellular signaling. Neu1, MMP-9 and neuromedin B GPCR form a complex with IRβ subunit on the cell surface. Oseltamivir phosphate (Tamiflu®), anti-Neu1 antibodies, broad range MMP inhibitors piperazine and galardin (GM6001), MMP-9 specific inhibitor (MMP-9i), and GPCR neuromedin B specific antagonist BIM-23127 dose-dependently inhibited Neu1 activity associated with insulin stimulated rat hepatoma cells (HTCs) that overly express human IRs (HTC-IR). Tamiflu, anti-Neu1 antibodies and MMP-9i attenuated phosphorylation of IRβ and insulin receptor substrate-1 (IRS1) associated with insulin-stimulated cells. Olanzapine, an antipsychotic agent associated with insulin resistance, induced Neu3 sialidase activity in WG544 or 1140F01 human sialidosis fibroblast cells genetically defective in Neu1. Neu3 antagonist 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA) and anti-Neu3 antibodies inhibited sialidase activity associated with olanzapine treated murine Neu4 knockout macrophage cells. Olanzapine attenuated phosphorylation of IGF-R and IRS1 associated with insulin-stimulated human wild-type fibroblast cells. Our findings identify a novel insulin receptor-signaling platform that is critically essential for insulin-induced IRβ tyrosine kinase activation and cellular signaling. Olanzapine-induced Neu3 sialidase activity attenuated insulin-induced IGF-R and IRS1 phosphorylation contributing to insulin resistance. PMID:24583283

  7. Cocoa-rich diet ameliorates hepatic insulin resistance by modulating insulin signaling and glucose homeostasis in Zucker diabetic fatty rats.

    Science.gov (United States)

    Cordero-Herrera, Isabel; Martín, María Ángeles; Escrivá, Fernando; Álvarez, Carmen; Goya, Luis; Ramos, Sonia

    2015-07-01

    Insulin resistance is the primary characteristic of type 2 diabetes and results from insulin signaling defects. Cocoa has been shown to exert anti-diabetic effects by lowering glucose levels. However, the molecular mechanisms responsible for this preventive activity and whether cocoa exerts potential beneficial effects on the insulin signaling pathway in the liver remain largely unknown. Thus, in this study, the potential anti-diabetic properties of cocoa on glucose homeostasis and insulin signaling were evaluated in type 2 diabetic Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed a control or cocoa-rich diet (10%), and Zucker lean animals received the control diet. ZDF rats supplemented with cocoa (ZDF-Co) showed a significant decrease in body weight gain, glucose and insulin levels, as well as an improved glucose tolerance and insulin resistance. Cocoa-rich diet further ameliorated the hepatic insulin resistance by abolishing the increased serine-phosphorylated levels of the insulin receptor substrate 1 and preventing the inactivation of the glycogen synthase kinase 3/glycogen synthase pathway in the liver of cocoa-fed ZDF rats. The anti-hyperglycemic effect of cocoa appeared to be at least mediated through the decreased levels of hepatic phosphoenolpyruvate carboxykinase and increased values of glucokinase and glucose transporter 2 in the liver of ZDF-Co rats. Moreover, cocoa-rich diet suppressed c-Jun N-terminal kinase and p38 activation caused by insulin resistance. These findings suggest that cocoa has the potential to alleviate both hyperglycemia and hepatic insulin resistance in type 2 diabetic ZDF rats.

  8. Oral carbohydrate loading with 18% carbohydrate beverage alleviates insulin resistance.

    Science.gov (United States)

    Tamura, Takahiko; Yatabe, Tomoaki; Kitagawa, Hiroyuki; Yamashita, Koichi; Hanazaki, Kazuhiro; Yokoyama, Masataka

    2013-01-01

    Preoperative 12.6% oral carbohydrate loading is an element of the Enhanced Recovery After Surgery (ERAS) protocol aimed at alleviating postoperative insulin resistance; however, in Japan, beverages with 18% carbohydrate content are generally used for preoperative carbohydrate loading. We investigated the effect of 18% carbohydrate loading on alleviating insulin resistance. Six healthy volunteers participated in this crossover-randomized study and were segregated into 2 groups: volunteers in the carbohydrate-loading group (group A) who fasted from after 9 pm and ingested 375 mL of a beverage containing 18% carbohydrate (ArginaidWaterTM; Nestle, Tokyo, Japan) between 9 pm and 12 pm, and 250 mL of the same liquid at 6:30 am. Volunteers in control group (group B) drank only water. At 8:30 am, a hyperinsulinemic normoglycemic clamp was initiated. Glucose infusion rate (GIR) and levels of ketone bodies and cytokines (IL-1β, IL-6, and TNF-α) before clamping were evaluated. p<0.05 was considered statistically significant. Levels of blood glucose, insulin, and cytokines at the start of the clamp were similar in both the groups. The GIR in group A was significantly higher than that in group B (11.5±2.4 vs 6.2±2.2 mg/kg/min, p=0.005), while blood ketone body levels were significantly lower in group A (22±4 vs 124±119 μmol/L, p=0.04). Preoperative 18% carbohydrate loading could prevent the decrease in insulin sensitivity and suppress catabolism in healthy volunteers. Thus, carbohydrate loading with a beverage with 18% carbohydrate content might contribute to improvements in perioperative management. PMID:23353610

  9. Insulin secretion after dietary supplementation with conjugated linoleic acids and n-3 polyunsaturated fatty acids in normal and insulin-resistant mice.

    OpenAIRE

    Sörhede Winzell, Maria; Pacini, Giovanni; Ahrén, Bo

    2006-01-01

    Insulin secretion after dietary supplementation with conjugated linoleic acids and n-3 polyunsaturated fatty acids in normal and insulin-resistance mice. Am J Physiol Endocrinol Metab 290: E347-E354, 2006. First published September 27, 2005; doi:10.1152/ajpendo.00163.2005.-Conjugated linoleic acids (CLAs) and n-3 polyunsaturated fatty acids (PUFAs) improve insulin sensitivity in insulin-resistant rodents. However, the effects of these fatty acids on insulin secretion are not known but are of ...

  10. Role of resistant starch in improving gut health, adiposity, and insulin resistance.

    Science.gov (United States)

    Keenan, Michael J; Zhou, June; Hegsted, Maren; Pelkman, Christine; Durham, Holiday A; Coulon, Diana B; Martin, Roy J

    2015-03-01

    The realization that low-glycemic index diets were formulated using resistant starch led to more than a decade of research on the health effects of resistant starch. Determination of the metabolizable energy of the resistant starch product allowed for the performance of isocaloric studies. Fermentation of resistant starch in rodent studies results in what appears to be a healthier gut, demonstrated by increased amounts of short-chain fatty acids, an apparent positive change in the microbiota, and increased gene expression for gene products involved in normal healthy proliferation and apoptosis of potential cancer cells. Additionally, consumption of resistant starch was associated with reduced abdominal fat and improved insulin sensitivity. Increased serum glucagon-like peptide 1 (GLP-1) likely plays a role in promoting these health benefits. One rodent study that did not use isocaloric diets demonstrated that the use of resistant starch at 8% of the weight of the diet reduced body fat. This appears to be approximately equivalent to the human fiber requirement. In human subjects, insulin sensitivity is increased with the feeding of resistant starch. However, only 1 of several studies reports an increase in serum GLP-1 associated with resistant starch added to the diet. This means that other mechanisms, such as increased intestinal gluconeogenesis or increased adiponectin, may be involved in the promotion of improved insulin sensitivity. Future research may confirm that there will be improved health if human individuals consume the requirement for dietary fiber and a large amount of the fiber is fermentable. PMID:25770258

  11. A single prior bout of exercise protects against palmitate-induced insulin resistance despite an increase in total ceramide content.

    Science.gov (United States)

    Thrush, A Brianne; Harasim, Ewa; Chabowski, Adrian; Gulli, Roberto; Stefanyk, Leslie; Dyck, David J

    2011-05-01

    Ceramide accumulation has been implicated in the impairment of insulin-stimulated glucose transport in skeletal muscle following saturated fatty acid (FA) exposure. Importantly, a single bout of exercise can protect against acute lipid-induced insulin resistance. The mechanism by which exercise protects against lipid-induced insulin resistance is not completely known but may occur through a redirection of FA toward triacylglycerol (TAG) and away from ceramide and diacylglycerol (DAG). Therefore, in the current study, an in vitro preparation was used to examine whether a prior bout of exercise could confer protection against palmitate-induced insulin resistance and whether the pharmacological [50 μM fumonisin B(1) (FB1)] inhibition of ceramide synthesis in the presence of palmitate could mimic the protective effect of exercise. Soleus muscle of sedentary (SED), exercised (EX), and SED in the presence of FB1 (SED+FB1) were incubated with or without 2 mM palmitate for 4 h. This 2-mM palmitate exposure impaired insulin-stimulated glucose transport (-28%, P TAG accumulation in the SED group (P TAG (P net increase in ceramide content in response to palmitate exposure in the EX group was not different compared with SED, despite the maintenance of insulin sensitivity. The incubation of soleus from SED rats with FB1 (SED+FB1) prevented the detrimental effects of palmitate and caused a redirection of FA toward TAG accumulation (P < 0.05). Therefore, this research suggests that although inhibiting ceramide accumulation can prevent the detrimental effects of palmitate, a single prior bout of exercise appears to protect against palmitate-induced insulin resistance, which may be independent of changes in ceramide content. PMID:21325642

  12. Large Size Cells in the Visceral Adipose Depot Predict Insulin Resistance in the Canine Model

    OpenAIRE

    Kabir, Morvarid; Stefanovski, Darko; Hsu, Isabel R.; Iyer, Malini; Woolcott, Orison O.; Zheng, Dan; Catalano, Karyn J.; Chiu, Jenny D.; Kim, Stella P.; Lisa N Harrison; Ionut, Viorica; Lottati, Maya; Richard N Bergman; Richey, Joyce M.

    2011-01-01

    Adipocyte size plays a key role in the development of insulin resistance. We examined longitudinal changes in adipocyte size and distribution in visceral (VIS) and subcutaneous (SQ) fat during obesity-induced insulin resistance and after treatment with CB-1 receptor antagonist, rimonabant (RIM) in canines. We also examined whether adipocyte size and/or distribution is predictive of insulin resistance. Adipocyte morphology was assessed by direct microscopy and analysis of digital images in pre...

  13. Androgen Excess Disorders in Women: The Severe Insulin-Resistant Hyperandrogenic Syndrome, HAIR-AN

    Directory of Open Access Journals (Sweden)

    Kristin M. Rager

    2006-01-01

    Full Text Available HAIR-AN syndrome (hyperandrogenism, insulin resistance, acanthosis nigricans is a subset of the polycystic ovary syndrome, where the patients demonstrate severe insulin resistance. It is theorized that both genetic and environmental factors, such as obesity, give rise to the development of HAIR-AN. Diagnosis is primarily clinical, with laboratory values lending further support. Treatment is aimed at decreasing insulin resistance, regulating ovulation, and decreasing acne, acanthosis nigricans, and hirsutism.

  14. Potential Roles of Stevia rebaudiana Bertoni in Abrogating Insulin Resistance and Diabetes: A Review

    OpenAIRE

    Nabilatul Hani Mohd-Radzman; Ismail, W. I. W.; Zainah Adam; Siti Safura Jaapar; Aishah Adam

    2013-01-01

    Insulin resistance is a key factor in metabolic disorders like hyperglycemia and hyperinsulinemia, which are promoted by obesity and may later lead to Type II diabetes mellitus. In recent years, researchers have identified links between insulin resistance and many noncommunicable illnesses other than diabetes. Hence, studying insulin resistance is of particular importance in unravelling the pathways employed by such diseases. In this review, mechanisms involving free fatty acids, adipocytokin...

  15. Association between insulin resistance and bone structure in non-diabetic postmenopausal women

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram V; Finkelstein, Joel S; Bouxsein, Mary L;

    2016-01-01

    CONTEXT: The clinical consequences of insulin resistance and hyperinsulinemia on bone remain largely unknown. OBJECTIVE: To evaluate the effect of insulin resistance on peripheral bone geometry, volumetric bone mineral density (vBMD), bone microarchitecture and estimated bone strength. DESIGN...... covariates (e.g., time since menopause, cigarette smoking, physical activity, prior use of osteoporosis medications or glucocorticoids). CONCLUSIONS: In non-diabetic, postmenopausal women, insulin resistance was associated with smaller bone size, greater volumetric bone mineral density and generally...

  16. Exercise Protects against Diet-Induced Insulin Resistance through Downregulation of Protein Kinase Cβ in Mice

    OpenAIRE

    Xiaoquan Rao; Jixin Zhong; Xiaohua Xu; Brianna Jordan; Santosh Maurya; Zachary Braunstein; Tse-Yao Wang; Wei Huang; Sudha Aggarwal; Muthu Periasamy; Sanjay Rajagopalan; Kamal Mehta; Qinghua Sun

    2013-01-01

    Physical exercise is an important and effective therapy for diabetes. However, its underlying mechanism is not fully understood. Protein kinase Cβ (PKCβ) has been suggested to be involved in the pathogenesis of obesity and insulin resistance, but the role of PKCβ in exercise-induced improvements in insulin resistance is completely unknown. In this study, we evaluated the involvement of PKCβ in exercise-attenuated insulin resistance in high-fat diet (HFD)-fed mice. PKCβ(-/-) and wild-type mice...

  17. Cardiac Insulin Resistance and MicroRNA Modulators

    Directory of Open Access Journals (Sweden)

    Lakshmi Pulakat

    2012-01-01

    Full Text Available Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS, and this disorder may be accentuated by chronic alcohol consumption. In conditions of over-nutrition, increased insulin (INS and angiotensin II (Ang II activate mammalian target for rapamycin (mTOR/p70 S6 kinase (S6K1 signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2, it also renders cardioprotection via increased Ang II receptor 2 (AT2R upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR↔AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy.

  18. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

    Science.gov (United States)

    Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

    2016-06-01

    Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. PMID:27016579

  19. New measure of insulin sensitivity predicts cardiovascular disease better than HOMA estimated insulin resistance.

    Directory of Open Access Journals (Sweden)

    Kavita Venkataraman

    Full Text Available CONTEXT: Accurate assessment of insulin sensitivity may better identify individuals at increased risk of cardio-metabolic diseases. OBJECTIVES: To examine whether a combination of anthropometric, biochemical and imaging measures can better estimate insulin sensitivity index (ISI and provide improved prediction of cardio-metabolic risk, in comparison to HOMA-IR. DESIGN AND PARTICIPANTS: Healthy male volunteers (96 Chinese, 80 Malay, 77 Indian, 21 to 40 years, body mass index 18-30 kg/m(2. Predicted ISI (ISI-cal was generated using 45 randomly selected Chinese through stepwise multiple linear regression, and validated in the rest using non-parametric correlation (Kendall's tau τ. In an independent longitudinal cohort, ISI-cal and HOMA-IR were compared for prediction of diabetes and cardiovascular disease (CVD, using ROC curves. SETTING: The study was conducted in a university academic medical centre. OUTCOME MEASURES: ISI measured by hyperinsulinemic euglycemic glucose clamp, along with anthropometric measurements, biochemical assessment and imaging; incident diabetes and CVD. RESULTS: A combination of fasting insulin, serum triglycerides and waist-to-hip ratio (WHR provided the best estimate of clamp-derived ISI (adjusted R(2 0.58 versus 0.32 HOMA-IR. In an independent cohort, ROC areas under the curve were 0.77±0.02 ISI-cal versus 0.76±0.02 HOMA-IR (p>0.05 for incident diabetes, and 0.74±0.03 ISI-cal versus 0.61±0.03 HOMA-IR (p<0.001 for incident CVD. ISI-cal also had greater sensitivity than defined metabolic syndrome in predicting CVD, with a four-fold increase in the risk of CVD independent of metabolic syndrome. CONCLUSIONS: Triglycerides and WHR, combined with fasting insulin levels, provide a better estimate of current insulin resistance state and improved identification of individuals with future risk of CVD, compared to HOMA-IR. This may be useful for estimating insulin sensitivity and cardio-metabolic risk in clinical and

  20. Obesity and insulin resistance in resistant hypertension: implications for the kidney.

    Science.gov (United States)

    Rao, Akhilesh; Pandya, Vishwam; Whaley-Connell, Adam

    2015-05-01

    There is recognition that the obesity epidemic contributes substantially to the increasing incidence of CKD and resistant hypertension (HTN). The mechanisms by which obesity promotes resistance are an area of active interest and intense investigation. It is thought that increases in visceral adiposity lead to a proinflammatory, pro-oxidative milieu that promote resistance to the metabolic actions of insulin. This resistance to insulin at the level of skeletal muscle tissue impairs glucose disposal/utilization through actions on the endothelium that include vascular rarefaction, reductions in vascular relaxation, and vascular remodeling. Insulin resistance derived from increased adipose tissue and obesity has system-wide implications for other tissue beds such as the kidney that affects blood pressure regulation. The additional autocrine and paracrine activities of adipose tissue contribute to inappropriate activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system that promote kidney microvascular remodeling, stiffness, and sodium (Na(+)) retention that in turn promote HTN and in the CKD patient, resistance. In this review, we will summarize the important mechanisms that link obesity to CKD as they relate to resistant HTN.

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

    International Nuclear Information System (INIS)

    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)

  2. Insulin resistance and serum parameters of iron status in type 2 diabetics

    International Nuclear Information System (INIS)

    Background: Type 2 diabetes mellitus (T2DM) is a predominant public health concern worldwide, accounting for 90% of the cases of diabetes globally. Pathogenesis of T2DM involves insulin resistance, defective insulin secretion and increased glucose production by the liver. Subclinical haemochromatosis has been considered as one of the probable causes of insulin resistance and diabetes mellitus. The aim of this study was to determine and correlate insulin resistance and serum parameters of iron status (serum ferritin and transferrin saturation) in type 2 diabetics. Methods: It was a correlational study. This study was conducted on sixty male patients with type 2 diabetes mellitus. Fasting blood sample was taken from each subject and analysed for glucose, haemoglobin, insulin, iron, Total Iron Binding Capacity (TIBC) and ferritin. Insulin resistance was determined by HOMA-IR index. Transferrin saturation was calculated from serum iron and TIBC. Data was analysed using SPSS-17. Results: There was significant positive correlation between insulin resistance and transferrin saturation, but there was no significant correlation of insulin resistance with blood haemoglobin, serum iron and serum ferritin in type 2 diabetics. Conclusion: Correlation between insulin resistance and transferrin saturation reveals that iron has negative impact on insulin sensitivity in type 2 diabetics. (author)

  3. Severe insulin resistance alters metabolism in mesenchymal progenitor cells.

    Science.gov (United States)

    Balhara, Bharti; Burkart, Alison; Topcu, Vehap; Lee, Youn-Kyoung; Cowan, Chad; Kahn, C Ronald; Patti, Mary-Elizabeth

    2015-06-01

    Donohue syndrome (DS) is characterized by severe insulin resistance due to mutations in the insulin receptor (INSR) gene. To identify molecular defects contributing to metabolic dysregulation in DS in the undifferentiated state, we generated mesenchymal progenitor cells (MPCs) from induced pluripotent stem cells derived from a 4-week-old female with DS and a healthy newborn male (control). INSR mRNA and protein were significantly reduced in DS MPC (for β-subunit, 64% and 89% reduction, respectively, P consumption in both the basal state (87% higher, P =.09) and in response to the uncoupler carbonyl cyanide-p-triflouromethoxyphenylhydrazone (2-fold increase, P =.06). Although mitochondrial DNA or mass did not differ, oxidative phosphorylation protein complexes III and V were increased in DS (by 37% and 6%, respectively; P < .05). Extracellular acidification also tended to increase in DS (91% increase, P = .07), with parallel significant increases in lactate secretion (34% higher at 4 h, P < .05). In summary, DS MPC maintain signaling downstream of the INSR, suggesting that IGF-1R signaling may partly compensate for INSR mutations. However, alterations in receptor expression and pathway-specific defects in insulin signaling, even in undifferentiated cells, can alter cellular oxidative metabolism, potentially via transcriptional mechanisms. PMID:25811318

  4. Hashimoto's hypothyroidism associated with insulin resistance in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Tešić Dragan

    2006-01-01

    Full Text Available Introduction. Thyroid peroxidase activity inhibiting immunoglobulins (anti-TPO Ab is a sign of autoimmune process in the thyroid gland. Association of hyperthyroidism and diabetes mellitus has been classically described. However, hypometabolic state, as a consequence of hypothyroidism, is not frequently linked with the biological activity of insulin. Case description. A 51-year old man was admitted to the Clinic with unregulated diabetes, untreated for 5 yrs. Insulin therapy was introduced one year before, with 96 units on admission. He had bowel movements every three days. BH 176cm, BW 120kg, a puffy face and swollen body. Fundus examination did not show specific diabetic leasions. Hepatic steatosis was present on ultra­sound examination. Occlusion of coronary arteries and superficial femoral artreries was present on angiography, and stenosis of carotid artreies on doppler duplex examination. HbAlc 14.7%. TSH 85.7 mIU/l. FT4 1.6 pmol/l, FT3 1.4. Anti TPOAb >600 IU/ml, triglycerides 2.26 mmol/l, HDL 1.15. cholesterolemia 10.0. Levothyroxine substitution was introduced starting with 25 mgr, gradually increasing up to 75 mgr. The need for insulin gradually decreased and finally it was switched to glibenclamide 5mg +0+2.5 mg. On discharge his FBG was 7.0 mmol/l. HOMA -B 52.3, HOMA-R 9.8. Discussion. We can conclude that in our patient secondary obesity caused deterioration of diabetes. After introduction of substitution therapy with levothyroxine, decrease of insulin resistance an J of cholesterol level was established. The duration of undiagnosed hypothyroidism can be a matter of speculation. However, the beneficial effect of normalized metabolism on atherosclerotic process will be obvious in the future. .

  5. 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

  6. 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...

  7. Hypolactasia is associated with insulin resistance in nonalcoholic steatohepatitis

    Science.gov (United States)

    de Campos Mazo, Daniel Ferraz; Mattar, Rejane; Stefano, José Tadeu; da Silva-Etto, Joyce Matie Kinoshita; Diniz, Márcio Augusto; Duarte, Sebastião Mauro Bezerra; Rabelo, Fabíola; Lima, Rodrigo Vieira Costa; de Campos, Priscila Brizolla; Carrilho, Flair José; Oliveira, Claudia P

    2016-01-01

    AIM To assess lactase gene (LCT)-13910C>T polymorphisms in Brazilian non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients in comparison with healthy controls. METHODS This was a transverse observational clinical study with NAFLD patients who were followed at the Hepatology Outpatient Unit of the Hospital das Clínicas, São Paulo, Brazil. The polymorphism of lactase non-persistence/lactase persistence (LCT-13910C>T) was examined by PCR-restriction fragment length polymorphism technique in 102 liver biopsy-proven NAFLD patients (steatosis in 9 and NASH in 93) and compared to those of 501 unrelated healthy volunteers. Anthropometric, clinical, biochemical and liver histology data were analyzed. Continuous variables were compared using the t or Mann-Whitney tests, and categorical data were compared with the Fisher’s exact test. Univariate logistic regression and multivariate logistic regression adjusted for gender and age were performed. RESULTS No differences in the LCT-13910 genotype frequencies were noted between the NAFLD patients (66.67% of the patients with steatosis were CC, 33.33% were CT, and none were TT; 55.91% of the patients with NASH were CC, 39.78% were CT, and 4.3% were TT; P = 0.941) and the healthy controls (59.12% were CC, 35.67% were CT, and 5.21% were TT) or between the steatosis and NASH patients. That is, the distribution of the lactase non-persistence/lactase persistence polymorphism (LCT-13910C>T) in the patients with NAFLD was equal to that in the general population. In the NASH patients, the univariate analysis revealed that the lactase non-persistence (low lactase activity or hypolactasia) phenotype was associated with higher insulin levels (23.47 ± 15.94 μU/mL vs 15.8 ± 8.33 μU/mL, P = 0.027) and a higher frequency of insulin resistance (91.84% vs 72.22%, P = 0.02) compared with the lactase persistence phenotype. There were no associations between the LCT genotypes and diabetes (P = 0

  8. Relationship between skin fold thickness and insulin resistance in the essential hypertensive patients in Vietnam

    Institute of Scientific and Technical Information of China (English)

    Toan C Nguyen; Khoa TA Pham; Quyen TL Do; Cuong T Nguyen; Diep D Nguyen Vinh G Le; Cong D Nguyen

    2005-01-01

    Previous studies reported a close relationship between obesity and insulin resistance in the essential hypertensive patients. Objective In this study, we examined the relationship between the skin fold thickness and insulin resistance then developed a formula to estimate the insulin resistance index according to the skin fold thickness in the essential hypertensive patients. Subjects and Methods Medical records of 80 patients (37 males, 43 females) were reviewed and the data were tabulated. Anthropometric indexes (including height, weight, waist circumference, hip circumference, and skins fold thickness at 5 fatty difference points on the Erdheim diagram), fasting plasma glucose and insulin concentration were recorded. The mean age was 57.0±9.2 years. The insulin resistance index was calculated following the Homeostasis Model Assessment (HOMA) formula. Results Compared with the group with BMI<23kg/m2, the group with BMI≥23 kg/m2 had higher fasting insulin concentration (8.85 ± 4.97 pmol/L vs 15.60 ± 8.70 pmol/L, P<0.001 ) and higher insulin resistance index in (2.15±1,24 vs 3.76±2.22, P<0.001). No significant difference in fasting plasma insulin concentration,insulin resistance index between male and female was observed (P>0.05). There was a positive correlation between skin fold thickness and the fasting insulin concentration and insulin resistance index. The skin fold thickness at point A8 had the best coefficient correlated with fasting plasma insulin(r=0.79, P<0.001) and insulin resistance index (r= 0.79, P < 0.001). A formula to estimate the insulin resistance index by skin fold thickness at point A8 as: Insulin resistance index = 0.12 × [skin fold thickness at A8 point (mm)] - 1.Conclusion: In the essential hypertensive patients, the formula to estimate insulin resistance index as 0.12 × [skin fold thickness at A8 point (mm)]-1 may predict accurately the level of insulin resistance.

  9. Hyperandrogenism-Insulin Resistance-Acanthosis Nigricans Syndrome

    Directory of Open Access Journals (Sweden)

    A. H. Dédjan

    2015-01-01

    Full Text Available Introduction. Female hyperandrogenism is a frequent motive of consultation. It is revealed by hirsutism, acne or seborrhea, and disorders in menstruation cycle combined or not with virilisation signs. Several etiologies are incriminated but the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome is rare. Observation. A 20-year-old girl, having had a five-year-old secondary amenorrhea. The exam revealed a patient, normotensive with a body mass index at 30 kg/m2 and a waist measurement of 120 cm, a severe hirsutism assessed to be 29 according to Ferriman Gallwey scale, virilisation signs of male morphotype, clitoridic hypertrophy and frontal alopecia, and an acanthosis nigricans behind the neck, in the armpits and elbows. The assessment carried out revealed testosteronemia at 1.28 ng/mL, which is more than twice the upper norm of the laboratory. Imaging studies were negative for both ovarian and adrenal masses. The retained diagnosis is HAIR-AN syndrome probably related to ovarian hyperthecosis and she was provided with androcur 50 mg/day and estradiol pills 2 mg/day and under hygiene-dietetic conditions. Conclusion. This case proves that HAIR-AN syndrome could be responsible for severe hyperandrogenism with virilisation signs. It must be retained after discarding the tumoral causes and when there are signs of insulin resistance.

  10. Periodontitis and Insulin Resistance: Casual or Causal Relationship?

    Directory of Open Access Journals (Sweden)

    Abhijit N. Gurav

    2012-12-01

    Full Text Available Insulin resistance (IR is now considered as a chronic and low level inflammatory condition. It is closely related to altered glucose tolerance, hypertriglyceridemia, abdominal obesity, and coronary heart disease. IR is accompanied by the increase in the levels of inflammatory cytokines like interleukin-1 and 6, tumor necrosis factor-α. These inflammatory cytokines also play a crucial part in pathogenesis and progression of insulin resistance. Periodontitis is the commonest of oral diseases, affecting tooth investing tissues. Pro-inflammatory cytokines are released in the disease process of periodontitis. Periodontitis can be attributed with exacerbation of IR. Data in the literature supports a "two way relationship" between diabetes and periodontitis. Periodontitis is asymptomatic in the initial stages of disease process and it often escapes diagnosis. This review presents the blurred nexus between periodontitis and IR, underlining the pathophysiology of the insidious link. The knowledge of the association between periodontitis and IR can be valuable in planning effectual treatment modalities for subjects with altered glucose homeostasis and diabetics. Presently, the studies supporting this association are miniscule. Further studies are mandatory to substantiate the role of periodontitis in the deterioration of IR.

  11. Targeted Disruption of ROCK1 Causes Insulin Resistance in Vivo*S⃞

    OpenAIRE

    Lee, Dae Ho; Shi, Jianjian; Jeoung, Nam Ho; Kim, Min Seon; Zabolotny, Janice M.; Lee, Sam W.; White, Morris F.; Wei, Lei; Kim, Young-Bum

    2009-01-01

    Insulin signaling is essential for normal glucose homeostasis. Rho-kinase (ROCK) isoforms have been shown to participate in insulin signaling and glucose metabolism in cultured cell lines. To investigate the physiological role of ROCK1 in the regulation of whole body glucose homeostasis and insulin sensitivity in vivo, we studied mice with global disruption of ROCK1. Here we show that, at 16–18 weeks of age, ROCK1-deficient mice exhibited insulin resistance, as reveale...

  12. Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology

    OpenAIRE

    Deshmukh, Atul S.

    2016-01-01

    Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabe...

  13. Effect of thiazolidinedione treatment on resistin levels in insulin resistant sprague dawley rats

    International Nuclear Information System (INIS)

    Insulin resistance is manifested by decreased effect of fixed quantity of insulin on glucose metabolism leading to type 2 diabetes mellitus. Visceral obesity has been positively correlated with insulin resistance but its mechanism is not fully defined. Insulin resistance may be the consequence of adipocytokines including visfatin and resistin. This study was designed to see the effect of thiazolidinediones on levels of resistin in insulin resistant rats. Methods: Ninety Sprague Dawley rats were randomly divided into three groups. Group I served as control. Rats in Group II and III were made insulin resistant diabetics. Group III was treated with rosiglitazone after development of diabetes. Plasma glucose, serum triglycerides, HDL, TG:HDL ratio and serum resistin levels were analysed. Results: Body weight and plasma glucose were significantly increased (p<0.05) along with TG:HDL ratio (p<0.05) in group II and group III at the end of 4th week. Serum resistin levels also increased significantly (p<0.05) in group II and III at the end of 4th week. Treatment of group III with rosiglitazone led to improvement in insulin resistance with decrease in serum resistin levels (p<0.05). Conclusion: Increased serum resistin level indicates insulin resistance and impending hyperglycaemia. Thiazolidinediones augment sensitivity of insulin to restore normoglycaemia by decreasing serum resistin level. (author)

  14. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    International Nuclear Information System (INIS)

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [3H]glucose and 2-deoxy[14C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats

  15. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  16. Deletion of exon 3 of the insulin receptor gene in a kindred with a familial form of insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wertheimer, E.; Barbetti, F.; Accili, D.; Taylor, S.I. [National Institutes of Health, Bethesda, MD (United States); Litvin, Y.; Ebstein, R.P.; Bennet, E.R.

    1994-05-01

    Molecular scanning techniques, such as denaturing gradient gel electrophoresis (DGGE), greatly facilitate screening candidate genes for mutations. The authors have used DGGE to screen for mutations in the insulin receptor gene in a family in which four of five daughters were affected by type A insulin resistance in association with acanthosis nigricans and hyperandrogenism. DGGE did not detect mutations in any of the 22 exons of the insulin receptor gene. Nevertheless, Southern blot analysis suggested that there was a deletion of exon 3 in the other paternal allele of the insulin receptor gene. Analysis of the father`s cDNA confirmed that exon 3 was deleted from mRNA molecules derived from one of his two alleles of the insulin receptor gene. Furthermore, the father was found to be hemizygous for a polymorphic sequence (GAC{sup Asp} at codon 234) in exon 3 that was not inherited by any of the five daughters. Instead, all five daughters inherited the paternal allele with the deletion mutation. They did not detect mutations in the mother`s insulin receptor gene. Furthermore, the clinical syndrome did not segregate with either of the mother`s two alleles of the insulin receptor gene. Although the youngest daughter inherited the mutant allele from her father, she was not clinically affected. The explanation for the incomplete penetrance is not known. These results emphasize the importance of specifically searching for deletion mutations when screening candidate genes for mutations. Furthermore, the existence of apparently asymptomatic carriers of mutations in the insulin receptor gene, such as the father in the present study, suggests that the prevalence of mutations in the insulin receptor gene may be higher than would be predicted on the basis of the observed prevalence of patients with extreme insulin resistance. 34 refs., 6 figs., 1 tab.

  17. 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.

    LENUS (Irish Health Repository)

    Morgan, Stuart A

    2009-11-01

    Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity.

  18. Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

    OpenAIRE

    Mohamad Hafizi Abu Bakar; Kian-Kai Cheng; Mohamad Roji Sarmidi; Harisun Yaakob; Hasniza Zaman Huri

    2015-01-01

    Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathwa...

  19. Plasma Adiponectin and Insulin Resistance in Korean Type 2 Diabetes Mellitus

    OpenAIRE

    Kim, Mi-Jin; Yoo, Kwang-Ha; Park, Hyung-Suk; Chung, Sang-Man; Jin, Choon-Jo; Lee, Yoen; Shin, Young-Goo; Chung, Choon-Hee

    2005-01-01

    Insulin resistance, which implies impairment of insulin signaling in the target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor-α, plasminogen activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin. Adiponectin was estimated to be a protective adipocytokine against atherosclerosis, and also to have an anti...

  20. Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design

    OpenAIRE

    Brunt Ardith; Rhee Yeong

    2011-01-01

    Abstract Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobari...

  1. The Comparison of Two Methods of Exercise (intense interval training and concurrent resistance- endurance training) on Fasting Sugar, Insulin and Insulin Resistance in Women with Mellitus Diabetes

    OpenAIRE

    F Bazyar; E Banitalebi; SE Amirhosseini

    2016-01-01

    Background & aim: Exercise is an important component of health and an integral approach to the management of diabetes mellitus. The purpose of this study was to compare the effects of intense interval training and concurrent resistance- endurance training on fasting sugar, insulin and insulin resistance in women with mellitus diabetes.   Methods: Fifty-two overweight female diabetic type 2 patients (aged 45-60 years old with fasting blood glucose≥ 126 mg/dl) were selected to p...

  2. 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...

  3. Insulin signal transduction in skeletal muscle : special consideration for insulin resistance and diabetes

    OpenAIRE

    Song, Xiao Mei

    2000-01-01

    This dissertation work is focused on the insulin-signal-transduction pathways to glucose transport in skeletal muscle from animal models of NIDDM. The overall objective is to determine the effectiveness of different pharmacological treatments to improve insulin action in skeletal muscle. Muscle-fiber-type-specific differences in insulin signal transduction was first considered. We noted increased insulin action on insulin signaling events including; IR, IRS- 1, IRS-2, PI...

  4. Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

    DEFF Research Database (Denmark)

    Nellemann, B.; Vendelbo, M.H.; Nielsen, Thomas Svava;

    2014-01-01

    Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting....

  5. A short leucocyte telomere length is associated with development of insulin resistance

    DEFF Research Database (Denmark)

    Verhulst, Simon; Dalgård, Christine; Labat, Carlos;

    2016-01-01

    AIMS/HYPOTHESIS: A number of studies have shown that leucocyte telomere length (LTL) is inversely associated with insulin resistance and type 2 diabetes mellitus. The aim of the present longitudinal cohort study, utilising a twin design, was to assess whether shorter LTL predicts insulin resistance...

  6. Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance

    NARCIS (Netherlands)

    Hoeks, J.; Herpen, N.A.; Mensink, M.R.; Moonen-Kornips, E.; Beurden, van D.; Hesselink, M.K.C.; Schrauwen, P.

    2010-01-01

    OBJECTIVE-Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we em

  7. Insulin Resistance Is Not Conserved in Myotubes Established from Women with PCOS

    DEFF Research Database (Denmark)

    Eriksen, Mette; Pørneki, Ann Dorte; Skov, Vibe;

    2010-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women, who often develop insulin resistance. We tested the hypothesis that insulin resistance in skeletal muscle of patients with polycystic ovary syndrome (PCOS) is an intrinsic defect, by investigating...

  8. Insulin resistance and the risk of stroke and stroke subtypes in the nondiabetic elderly

    NARCIS (Netherlands)

    R.G. Wieberdink (Renske); P.J. Koudstaal (Peter Jan); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); M.M.B. Breteler (Monique); M. Arfan Ikram

    2012-01-01

    textabstractInsulin resistance, which plays a key role in the development of diabetes mellitus, is a putative modifiable risk factor for stroke. The aim of this study was to investigate if markers of insulin resistance were associated with risk of stroke in the general elderly population. This study

  9. Insulin resistance and risk of venous thromboembolism : results of a population-based cohort study

    NARCIS (Netherlands)

    Van Schouwenburg, I. M.; Mahmoodi, B. K.; Veeger, N. J. G. M.; Bakker, S. J. L.; Kluin-Nelemans, H. C.; Meijer, K.; Gansevoort, R. T.

    2012-01-01

    Background: Obesity is an established risk factor for venous thromboembolism (VTE), but it is uncertain how this is mediated. Insulin resistance has a central role in the pathophysiology of the metabolic effects of obesity. Objective: We aimed to investigate whether insulin resistance is a risk fact

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

    OpenAIRE

    Pikee Saxena; Anupam Prakash; Aruna Nigam

    2011-01-01

    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 fact...

  11. Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism

    OpenAIRE

    ÇAKIR, Evrim; Topaloğlu, Oya; BOZKURT, Nujen ÇOLAK; BAYRAKTAR, Başak KARBEK

    2014-01-01

    Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). Materials and methods: This was a prospective case-controlled study....

  12. Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    Biagio Arcidiacono

    2012-01-01

    Full Text Available Insulin resistance is common in individuals with obesity or type 2 diabetes (T2D, in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance and the increase in bioavailable insulin-like growth factor I (IGF-I appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG, whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increased risk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarize recent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression.

  13. Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.

    Science.gov (United States)

    del Campo, José A; López, Reyes Aparcero; Romero-Gómez, Manuel

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C. PMID:20460925

  14. Association of obesity and insulin resistance with asthma and aeroallergen sensitization

    DEFF Research Database (Denmark)

    Husemoen, L L N; Glümer, C; Lau, C;

    2008-01-01

    BACKGROUND: It has been hypothesized that obesity and insulin resistance may play a role in the development of asthma and allergy. The aim of the study was to examine the association of obesity and insulin resistance with asthma and aeroallergen sensitization. METHODS: Cross-sectional population...... and aeroallergen sensitization. The homeostasis model assessment of insulin resistance was used to estimate the degree of insulin resistance. Body mass index, waist-to-hip ratio, and waist circumference were used as measures of obesity. Data were analyzed by multiple logistic regression analyses. RESULTS: Obesity...... was associated with increased risk of aeroallergen sensitization as well as allergic and nonallergic asthma. Insulin resistance was asssociated with aeroallergen sensitization and allergic asthma, but not nonallergic asthma. The associations of obesity with aeroallegen sensitization and allergic asthma became...

  15. Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Møller, Niels; Juhl, Claus;

    2012-01-01

    of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development.......047), whereas first phase and pulsatile insulin secretion were unaffected. Coinciding with the CNI induced improved insulin sensitivity, glucose oxidation rates increased, while insulin clearance rates decreased, only non-significantly. Tac singularly lowered hsCRP concentrations, otherwise no changes were...

  16. Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans.

    Science.gov (United States)

    Kullmann, Stephanie; Heni, Martin; Hallschmid, Manfred; Fritsche, Andreas; Preissl, Hubert; Häring, Hans-Ulrich

    2016-10-01

    Ever since the brain was identified as an insulin-sensitive organ, evidence has rapidly accumulated that insulin action in the brain produces multiple behavioral and metabolic effects, influencing eating behavior, peripheral metabolism, and cognition. Disturbances in brain insulin action can be observed in obesity and type 2 diabetes (T2D), as well as in aging and dementia. Decreases in insulin sensitivity of central nervous pathways, i.e., brain insulin resistance, may therefore constitute a joint pathological feature of metabolic and cognitive dysfunctions. Modern neuroimaging methods have provided new means of probing brain insulin action, revealing the influence of insulin on both global and regional brain function. In this review, we highlight recent findings on brain insulin action in humans and its impact on metabolism and cognition. Furthermore, we elaborate on the most prominent factors associated with brain insulin resistance, i.e., obesity, T2D, genes, maternal metabolism, normal aging, inflammation, and dementia, and on their roles regarding causes and consequences of brain insulin resistance. We also describe the beneficial effects of enhanced brain insulin signaling on human eating behavior and cognition and discuss potential applications in the treatment of metabolic and cognitive disorders. PMID:27489306

  17. Effect of Acupuncture on Insulin Resistance in Non-insulin Dependent Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    LIU Zhi-cheng; SUN Feng-min; ZHU Miao-hua; WANG Xin-zheng

    2004-01-01

    观察46例NIDDM患者针灸治疗前后空腹血糖(FBS)、胰岛素(INS)、胰岛素敏感性指数(ISI)及INS拮抗激素的变化.针灸治疗NIDDM获得了良好的临床疗效.同时患者FBS、INS含量明显回降,ISI显著回升,这种变化程度与疗效有关;患者INS拮抗激素和脂质的水平出现了良性改变.针灸对NIDDM机体的内分泌、糖和脂质代谢具有良性调整作用.提示针灸纠正NIDDM IR可能是治疗作用的关键性因素之一.%The fasting blood sugar (FBS), blood insulin (INS), insulin sensitivity index (ISI) and resistant hormone of INS in 46 patients with NIDDM were observed before and after the treatment. It was showed that the good effect was achieved in the cases by acupuncture and moxibustion, while the contents of FBS and INS in plasma were all decreased and ISI was increased in the cases treated by acupuncture and moxibustion, the degree of decrease of FBS and INS, and increase of ISI being closely related to therapeutic effect. The level of resistant hormone of INS and lipid in patients tend to normal level. Acupuncture and moxibustion had a good regulatory effect on the function of endocrine,sugar and lipid metabolism. It suggests that IR can be corrected by acupuncture and moxibustion,which is a key to therapeutic effect.

  18. Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice.

    Science.gov (United States)

    Foti, Daniela; Chiefari, Eusebio; Fedele, Monica; Iuliano, Rodolfo; Brunetti, Leonardo; Paonessa, Francesco; Manfioletti, Guidalberto; Barbetti, Fabrizio; Brunetti, Arturo; Croce, Carlo M; Fusco, Alfredo; Brunetti, Antonio

    2005-07-01

    Type 2 diabetes mellitus is a widespread disease, affecting millions of people globally. Although genetics and environmental factors seem to have a role, the cause of this metabolic disorder is largely unknown. Here we report a genetic flaw that markedly reduced the intracellular expression of the high mobility group A1 (HMGA1) protein, and adversely affected insulin receptor expression in cells and tissues from four subjects with insulin resistance and type 2 diabetes. Restoration of HMGA1 protein expression in subjects' cells enhanced INSR gene transcription, and restored cell-surface insulin receptor protein expression and insulin-binding capacity. Loss of Hmga1 expression, induced in mice by disrupting the Hmga1 gene, considerably decreased insulin receptor expression in the major targets of insulin action, largely impaired insulin signaling and severely reduced insulin secretion, causing a phenotype characteristic of human type 2 diabetes. PMID:15924147

  19. Reduction of insulinotropic properties of GLP-1 and GIP after glucocorticoid-induced insulin resistance

    DEFF Research Database (Denmark)

    Eriksen, Marie; Jensen, David H; Tribler, Siri;

    2015-01-01

    AIMS/HYPOTHESIS: We evaluated the insulinotropic properties of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in healthy individuals at risk of developing type 2 diabetes before and after glucocorticoid-induced insulin resistance. METHODS: Nineteen healthy....... In addition, first-phase insulin responses were determined at 7 mmol/l and 15 mmol/l and second-phase insulin responses at 7 mmol/l. RESULTS: After dexamethasone treatment, all 19 participants had increased insulin resistance (HOMA-IR and insulin sensitivity index [M/I] values) and 2 h plasma glucose...... concentrations, while beta cell function indices generally increased according to the increased resistance. First-phase insulin responses induced by GLP-1 and GIP at 7 mmol/l and maximal beta cell secretory capacity did not differ before and after dexamethasone, while second-phase responses to 7 mmol/l and first...

  20. Does Inflammation Mediate the Association Between Obesity and Insulin Resistance?

    Science.gov (United States)

    Adabimohazab, Razieh; Garfinkel, Amanda; Milam, Emily C; Frosch, Olivia; Mangone, Alexander; Convit, Antonio

    2016-06-01

    In adult obesity, low-grade systemic inflammation is considered an important step in the pathogenesis of insulin resistance (IR). The association between obesity and inflammation is less well established in adolescents. Here, we ascertain the importance of inflammation in IR among obese adolescents by utilizing either random forest (RF) classification or mediation analysis approaches. The inflammation balance score, composed of eight pro- and anti-inflammatory makers, as well as most of the individual inflammatory markers differed significantly between lean and overweight/obese. In contrast, adiponectin was the only individual marker selected as a predictor of IR by RF, and the balance score only revealed a medium-to-low importance score. Neither adiponectin nor the inflammation balance score was found to mediate the relationship between obesity and IR. These findings do not support the premise that low-grade systemic inflammation is a key for the expression of IR in the human. Prospective longitudinal studies should confirm these findings.

  1. Molecular mechanisms of insulin resistance in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Mark W Douglas; Jacob George

    2009-01-01

    It is now widely recognized that chronic hepatitis C (CHC) is associated with insulin resistance (IR) and type 2 diabetes, so can be considered a metabolic disease. IR is most strongly associated with hepatitis C virus (HCV) genotype 1, in contrast to hepatic steatosis, which is associated with genotype 3 infection. Apart from the well-described complications of diabetes, IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma. More recently, it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined. This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.

  2. Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats.

    Science.gov (United States)

    Wang, Zhong Q; Zhang, Xian H; Russell, James C; Hulver, Matthew; Cefalu, William T

    2006-02-01

    Chromium is one of the few trace minerals for which a specific cellular mechanism of action has not been identified. Recent in vitro studies suggest that chromium supplementation may improve insulin sensitivity by enhancing insulin receptor signaling, but this has not been demonstrated in vivo. We investigated the effect of chromium supplementation on insulin receptor signaling in an insulin-resistant rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and based on calculated water intake, rats randomized to CrPic received 80 microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis) biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin stimulation to assess insulin signaling. Obese rats treated with CrPic had significantly improved glucose disposal rates and demonstrated a significant increase in insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle compared with obese controls. The increase in cellular signaling was not associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt. However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower in obese rats administered CrPic than obese controls. When corrected for protein content, PTP1B activity was also significantly lower in obese rats administered CrPic than obese controls. Our data suggest that chromium supplementation of obese, insulin-resistant rats may improve insulin action by enhancing intracellular signaling.

  3. The triglyceride content in skeletal muscle is associated with hepatic but not peripheral insulin resistance in elderly twins

    DEFF Research Database (Denmark)

    Grunnet, L G; Laurila, Esa; Hansson, Ola;

    2012-01-01

    Total muscle triglyceride (MT) content has been associated with insulin resistance. We investigated the predictors and impact of MT on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins.......Total muscle triglyceride (MT) content has been associated with insulin resistance. We investigated the predictors and impact of MT on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins....

  4. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yan-Jie [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Juan, Chi-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Kwok, Ching-Fai [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hsu, Yung-Pei [Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Shih, Kuang-Chung [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chen, Chin-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Ho, Low-Tone, E-mail: ltho@vghtpe.gov.tw [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China)

    2015-05-08

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance, ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway

  5. Exercise protects against diet-induced insulin resistance through downregulation of protein kinase Cβ in mice.

    Directory of Open Access Journals (Sweden)

    Xiaoquan Rao

    Full Text Available Physical exercise is an important and effective therapy for diabetes. However, its underlying mechanism is not fully understood. Protein kinase Cβ (PKCβ has been suggested to be involved in the pathogenesis of obesity and insulin resistance, but the role of PKCβ in exercise-induced improvements in insulin resistance is completely unknown. In this study, we evaluated the involvement of PKCβ in exercise-attenuated insulin resistance in high-fat diet (HFD-fed mice. PKCβ(-/- and wild-type mice were fed a HFD with or without exercise training. PKC protein expression, body and tissue weight change, glucose and insulin tolerance, metabolic rate, mitochondria size and number, adipose inflammation, and AKT activation were determined to evaluate insulin sensitivity and metabolic changes after intervention. PKCβ expression decreased in both skeletal muscle and liver tissue after exercise. Exercise and PKCβ deficiency can alleviate HFD-induced insulin resistance, as evidenced by improved insulin tolerance. In addition, fat accumulation and mitochondrial dysfunction induced by HFD were also ameliorated by both exercise and PKCβ deficiency. On the other hand, exercise had little effect on PKCβ(-/- mice. Further, our data indicated improved activation of AKT, the downstream signal molecule of insulin, in skeletal muscle and liver of exercised mice, whereas PKCβ deficiency blunted the difference between sedentary and exercised mice. These results suggest that downregulation of PKCβ contributes to exercise-induced improvement of insulin resistance in HFD-fed mice.

  6. Analysis of in vitro insulin-resistance models and their physiological relevance to in vivo diet-induced adipose insulin resistance.

    Science.gov (United States)

    Lo, Kinyui Alice; Labadorf, Adam; Kennedy, Norman J; Han, Myoung Sook; Yap, Yoon Sing; Matthews, Bryan; Xin, Xiaofeng; Sun, Lei; Davis, Roger J; Lodish, Harvey F; Fraenkel, Ernest

    2013-10-17

    Diet-induced obesity (DIO) predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but what aspects of the in vivo responses are captured by these models remains unknown. We use global RNA sequencing to investigate changes induced by TNF-α, hypoxia, dexamethasone, high insulin, and a combination of TNF-α and hypoxia, comparing the results to the changes in white adipose tissue from DIO mice. We found that different in vitro models capture distinct features of DIO adipose insulin resistance, and a combined treatment of TNF-α and hypoxia is most able to mimic the in vivo changes. Using genome-wide DNase I hypersensitivity followed by sequencing, we further examined the transcriptional regulation of TNF-α-induced insulin resistance, and we found that C/EPBβ is a potential key regulator of adipose insulin resistance.

  7. Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Kinyui Alice Lo

    2013-10-01

    Full Text Available Diet-induced obesity (DIO predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but what aspects of the in vivo responses are captured by these models remains unknown. We use global RNA sequencing to investigate changes induced by TNF-α, hypoxia, dexamethasone, high insulin, and a combination of TNF-α and hypoxia, comparing the results to the changes in white adipose tissue from DIO mice. We found that different in vitro models capture distinct features of DIO adipose insulin resistance, and a combined treatment of TNF-α and hypoxia is most able to mimic the in vivo changes. Using genome-wide DNase I hypersensitivity followed by sequencing, we further examined the transcriptional regulation of TNF-α-induced insulin resistance, and we found that C/EPBβ is a potential key regulator of adipose insulin resistance.

  8. Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men

    Science.gov (United States)

    Parker, Lewan; Stepto, Nigel K.; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell; Hare, David L.; Levinger, Itamar

    2016-01-01

    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1–3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE.

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

    Science.gov (United States)

    Saxena, Pikee; Prakash, Anupam; Nigam, Aruna

    2011-01-01

    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. PMID:21772735

  10. 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.

  11. Chronic TNF-a neutralization does not improve insulin resistance or endothelial function in "healthy" men with metabolic syndrome

    NARCIS (Netherlands)

    Wascher, T.C.; Lindeman, J.H.N.; Sourij, H.; Kooistra, T.; Pacini, G.; Roden, M.

    2011-01-01

    The possible contribution of tumor necrosis factor-a (TNF-a) to the development of obesity associated insulin resistance in humans is still controversial. Our study investigated the effect of TNF-a neutralization on insulin resistance in healthy, obese and insulin resistant men. We performed a prosp

  12. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independently of obesity

    DEFF Research Database (Denmark)

    Scott, Robert A; Fall, Tove; Pasko, Dorota;

    2014-01-01

    .31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of...

  13. Silymarin induces insulin resistance through an increase of phosphatase and tensin homolog in Wistar rats.

    Directory of Open Access Journals (Sweden)

    Kai-Chun Cheng

    Full Text Available BACKGROUND AND AIMS: Phosphatase and tensin homolog (PTEN is a phosphoinositide phosphatase that regulates crucial cellular functions, including insulin signaling, lipid and glucose metabolism, as well as survival and apoptosis. Silymarin is the active ingredient in milk thistle and exerts numerous effects through the activation of PTEN. However, the effect of silymarin on the development of insulin resistance remains unknown. METHODS: Wistar rats fed fructose-rich chow or normal chow were administered oral silymarin to identify the development of insulin resistance using the homeostasis model assessment of insulin resistance and hyperinsulinemic- euglycemic clamping. Changes in PTEN expression in skeletal muscle and liver were compared using western blotting analysis. Further investigation was performed in L6 cells to check the expression of PTEN and insulin-related signals. PTEN deletion in L6 cells was achieved by small interfering ribonucleic acid transfection. RESULTS: Oral administration of silymarin at a dose of 200 mg/kg once daily induced insulin resistance in normal rats and enhanced insulin resistance in fructose-rich chow-fed rats. An increase of PTEN expression was observed in the skeletal muscle and liver of rats with insulin resistance. A decrease in the phosphorylation of Akt in L6 myotube cells, which was maintained in a high-glucose condition, was also observed. Treatment with silymarin aggravated high-glucose-induced insulin resistance. Deletion of PTEN in L6 cells reversed silymarin-induced impaired insulin signaling and glucose uptake. CONCLUSIONS: Silymarin has the ability to disrupt insulin signaling through increased PTEN expression. Therefore, silymarin should be used carefully in type-2 diabetic patients.

  14. Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)

    DEFF Research Database (Denmark)

    Bingley, Polly J; Mahon, Jeffrey L; Gale, Edwin A M;

    2008-01-01

    OBJECTIVE: Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers......-up was 4.21 years, and 105 individuals developed diabetes. Oral and intravenous glucose tolerance tests were performed at baseline; antibodies to GAD, IA-2, and insulin were determined by radioimmunoassay; and insulin resistance was estimated by homeostasis model assessment. Risk was assessed by Cox...... glucose tolerance test (P insulin resistance (HOMA2-IR) achieved only borderline significance (P = 0.06). HOMA2-IR was an independent determinant in participants with loss of FPIR (P = 0...

  15. Vitamin D and insulin resistance%维生素D与胰岛素抵抗

    Institute of Scientific and Technical Information of China (English)

    张珍; 刘春燕

    2013-01-01

    Vitamin D deficiency is closely related to insulin resistance , and vitamin D replacement can significantly enhance insulin sensitivity. This paper focuses on the relationship of insulin resistance with vitamin D and the gene polymorphism of VD receptor ( VDR) , as well as the mechanism of vitamin D improving insulin resistance .%维生素(Vitamin,Vit)D缺乏与胰岛素抵抗(insulin resistance,IR)密切相关,而补充VitD治疗能显著增强胰岛素的敏感性.文中将对VitD与IR的关系、维生素D受体(vitamin D receptor,VDR)基因多态性与IR的关系及VitD改善IR的作用机制等方面作一综述.

  16. The Comparison of Two Methods of Exercise (intense interval training and concurrent resistance- endurance training on Fasting Sugar, Insulin and Insulin Resistance in Women with Mellitus Diabetes

    Directory of Open Access Journals (Sweden)

    F Bazyar

    2016-05-01

    Full Text Available Background & aim: Exercise is an important component of health and an integral approach to the management of diabetes mellitus. The purpose of this study was to compare the effects of intense interval training and concurrent resistance- endurance training on fasting sugar, insulin and insulin resistance in women with mellitus diabetes.   Methods: Fifty-two overweight female diabetic type 2 patients (aged 45-60 years old with fasting blood glucose≥ 126 mg/dl were selected to participate in the present study. Participants were assigned to intense interval training group (N=17, concurrent resistance- endurance training group (N=17 and control group (N=18. The exercises incorporated 10 weeks of concurrent resistance- endurance training and intense interval training. Fasting blood sugar, serum insulin concentrations levels were measured. Concurrent training group trained eight weeks, three times a week of endurance training at 60% of maximum heart rate (MHR and two resistance training sessions per week with 70% of one repetition maximum (1-RM. Intense interval training group trained for eight weeks, three sessions per week for 4 to 10 repeats Wingate test on the ergometer 30s performed with maximum effort. The control group did no systematic exercise. At the end of experiment 42 subjects were succeed and completed the study period, and 10 subjects were removed due to illness and absence in the exercise sessions. Fasting blood sugar and insulin levels 24 hours before and 48 hours after the last training session was measured.   Results: The findings indicated that in periodic fasting, the blood sugar in intensive training group had a marked decrease (p= 0.000 however, the fasting blood sugar of exercise and power stamina groups reduced significantly (p=0.062. The results showed no significant difference between the groups (171/0 p =0.171. Fasting insulin (p <0.001 and insulin resistance (0001/0 = p=0.001 in periodic intensive training group were

  17. Growth Hormone, Insulin Resistance Index, Lipid Profile, and Cardiorespiratory Function in Obese and Lean Inactive Young Men: Correlations with Plasma Acylated Ghrelin Levels

    Directory of Open Access Journals (Sweden)

    Hasan Matinhomaee

    2011-01-01

    Full Text Available Introduction: Plasma ghrelin is influenced by nutritional status and is thought to play a role in acute and chronic regulating of food intake and body weight. The purpose of this study was to compare GH, insulin resistance index, lipid profile, and cardiorespiratory function in obese and lean inactive young men and determine their relationships with plasma acylated ghrelin levels. Methods: Study design of this research was causal-comparative. Obese (n=19, BMI: 31.0 kg/m2 and lean (n=19, BMI: 18.5 kg/m2 young men, without experience of regular physical activity during the previous six months, were selected. After 12 h fasting (at 8 a.m., blood samples were collected to determine blood parameter levels. Also, maximal oxygen uptake (as indicator of cardiorespiratory function of subjects was assessed. Results: Insulin levels and HOMA-IR (insulin resistance index were higher, and GH, acylated ghrelin and maximal oxygen uptake levels were lower in obese men compared to lean men (P0.01. Plasma acylated ghrelin concentrations were negatively correlated to body mass, body fat percent, body mass index, insulin and HOMA-IR, and positively correlated to GH levels and maximal oxygen uptake (P0.01.Conclusion: Obese and lean inactive young men had different levels of acylated ghrelin, GH, insulin, insulin resistance index, cardiorespiratory function and body fat percent. Body fat percent, insulin, and GH levels appear to be the strongest determinant factors of acylated ghrelin levels.

  18. Consumption of a High-Fat Diet Induces Central Insulin Resistance Independent of Adiposity

    OpenAIRE

    Clegg, Deborah J.; Gotoh, Koro; Kemp, Christopher; Wortman, Matthew D.; Benoit, Stephen C.; Brown, Lynda M.; D’Alessio, David; Tso, Patrick; Seeley, Randy J.; Woods, Stephen C

    2011-01-01

    Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of...

  19. Antidiabetogenic Effects of Chromium Mitigate Hyperinsulinemia-Induced Cellular Insulin Resistance via Correction of Plasma Membrane Cholesterol Imbalance

    OpenAIRE

    Horvath, Emily M.; Tackett, Lixuan; McCarthy, Alicia M.; Raman, Priya; Brozinick, Joseph T.; Elmendorf, Jeffrey S.

    2007-01-01

    Previously, we found that a loss of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2)-regulated filamentous actin (F-actin) structure contributes to insulin-induced insulin resistance. Interestingly, we also demonstrated that chromium picolinate (CrPic), a dietary supplement thought to improve glycemic status in insulin-resistant individuals, augments insulin-regulated glucose transport in insulin-sensitive 3T3-L1 adipocytes by lowering PM cholesterol. Here, to gain mechanisti...

  20. A peroxiredoxin, PRDX-2, is required for insulin secretion and insulin/IIS-dependent regulation of stress resistance and longevity.

    Science.gov (United States)

    Oláhová, Monika; Veal, Elizabeth A

    2015-08-01

    Peroxiredoxins (Prx) are abundant thiol peroxidases with a conserved anti-ageing role. In contrast to most animals, the nematode worm, Caenorhabditis elegans, encodes a single cytosolic 2-Cys Prx, PRDX-2, rendering it an excellent model for examining how peroxiredoxins affect animal physiology and ageing. Our previous work revealed that, although PRDX-2 protects against the toxicity of peroxides, enigmatically, prdx-2-mutant animals are hyper-resistant to other forms of oxidative stress. Here, we have investigated the basis for this increased resistance. Mammalian FOXO and Nrf2 transcription factors directly promote the expression of a range of detoxification enzymes. We show that the FOXO orthologue, DAF-16, and the Nrf2 orthologue, SKN-1, are required for the increased stress resistance of prdx-2-mutant worms. Our data suggest that PRDX-2 is required for normal levels of insulin secretion and hence the inhibition of DAF-16 and SKN-1 by insulin/IGF-1-like signalling (IIS) under nutrient-rich conditions. Intriguingly, loss of PRDX-2 increases DAF-16 and SKN-1 activities sufficiently to increase arsenite resistance without initiating other IIS-inhibited processes. Together, these data suggest that loss of peroxiredoxin function may increase stress resistance by reducing insulin secretion, but that further changes in insulin signalling are required for the reprogramming of development and fat metabolism. In addition, we reveal that the temperature-dependent prolongevity function of PRDX-2 is required for the extended lifespan associated with several pathways, including further reductions in IIS. PMID:25808059

  1. 胰岛素抵抗对急性非ST段抬高型心肌梗死非糖尿病患者早期梗死范围及心功能的影响%Impact of insulin resistance on early infarction size and cardiac function of non-diabetic patients with acute NSTEMI

    Institute of Scientific and Technical Information of China (English)

    谢刚; 曹树军; 王峙峰

    2015-01-01

    Objective To observe the impact of insulin resistance (IR) on infarct size and cardiac function of non-diabetic patients at early stage of acute NSTEMI.Methods Sixty-nine non-diabetic patients with NSTEMI in Chinese PLA General Hospital from January 6 to July 31 in 2014 were consecutively enrolled in the study. 18-lead ECG was acquired within 10 minutes after admission of each patient, and the sum of ST-segments depression (Sum STD) was calculated. On the 2nd day, the values of left ventricular ejection fraction (LVEF), left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) were assessed in all patients with echocardiogram. The homeostatic model assessment index (HOMA index) was also determined on the 2nd day after admission. The patients were divided into insulin resistance (IR) group (HOMA index≥1.7) and non insulin resistance (NIR) group (HOMA index0.05). Compared with NIR group, the Sum STD and the peak release of CK, CK-MB, NT-pro BNP in patients of IR group was significantly higher (P<0.01). The average values of left ventricular end diastolic volume (LVEDV) were similar between two groups while the average value of left ventricular end systolic volume (LVESV) in IR group was significantly higher than in IR group (P<0.01). The average value of left ventricular eject fraction (LVEF) in IR group was significantly decreased compared with NIR group (P<0.01).Conclusion This research shows high incidence of acute IR at early stage of NSTEMI in non-diabetic patients. The non-diabetic patients with IR has larger infarct size and more seriously impaired left ventricular systolic function than patients without IR at early stage of acute NSTEMI.%目的:观察胰岛素抵抗对急性非ST段抬高型心肌梗死(non ST-segment elevation myocardial infartion,NSTEMI)的非糖尿病患者早期梗死范围及心功能的影响。方法连续选取2014年1月6日-7月31日解放军总医院心血管内科监护室收治的69例

  2. Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

    Directory of Open Access Journals (Sweden)

    Iagher Fabiola

    2011-04-01

    Full Text Available Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG (4 mg/g body weight was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C, coconut fat-treated normal weight group (CO, fish oil-treated normal weight group (FO, obese control group (Ob, coconut fat-treated obese group (ObCO and fish oil-treated obese group (ObFO. Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30% and triacylglycerol (TG; 33% compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

  3. Insulin resistance modifies the association between obesity and current asthma in adults.

    Science.gov (United States)

    Cardet, Juan Carlos; Ash, Samuel; Kusa, Tope; Camargo, Carlos A; Israel, Elliot

    2016-08-01

    Insulin resistance potentiates the association between obesity and childhood asthma, but this relationship appears inconsistent in relatively small studies of adults. We investigated effect modification in adults using the National Health and Nutrition Examination Survey 2003-2012, a large, nationally representative database.Insulin resistance and a history of physician-diagnosed current asthma were obtained from 12 421 adults, ages 18-85 years. We used logistic regression to determine associations between obesity and current asthma, adjusting for age, sex, race/ethnicity, poverty income ratio and smoking status. An interaction term evaluated effect modification by insulin resistance of the obesity-asthma association.As expected, obesity was positively associated with current asthma. Insulin resistance modified this association, with obesity measured as body mass index, waist circumference or waist-to-height ratio. The relationship between obesity and current asthma was stronger with increasing insulin resistance tertiles (OR 2.05, 95% CI 2.76-3.00; p-value for interaction 0.03). This association was robust to adjustments for other components of the metabolic syndrome (hypertriglyceridaemia, hypertension, hyperglycaemia and systemic inflammation). None of these components were themselves effect modifiers of the obesity-asthma association.In this large, nationally representative sample, insulin resistance modified the association between obesity and current asthma in adults. Targeting insulin resistance may represent a novel therapeutic strategy for obese patients with asthma. PMID:27103388

  4. Hypertension and insulin resistance are not directly related in obese dogs.

    Science.gov (United States)

    Rocchini, Albert P; Yang, John Q; Gokee, Amy

    2004-05-01

    In dogs fed a high-fat diet, we determined whether there was a direct relation between obesity-induced insulin resistance and obesity-induced hypertension. Thirty-six adult mongrel dogs were chronically instrumented and assigned to receive either a high-fat diet alone (n=7) or a high-fat diet combined with a low-sodium diet plus furosemide (n=6), prazosin plus atenolol (n=7), clonidine (n=10), or aspirin (n=6). Blood pressure, heart rate, and body weight were measured daily. Insulin resistance was assessed with a single-dose euglycemic hyperinsulinemic clamp (2 mU x kg(-1) x min(-1)) before and after 1, 3, and 6 weeks of the high-fat diet. The low-salt diet plus furosemide, prazosin plus atenolol, and clonidine treatments prevented the hypertension associated with feeding the dogs a high-fat diet. Only clonidine treatment totally prevented the development of insulin resistance, and high-dose aspirin, known to prevent insulin resistance by inhibition of the activity of IkappaB kinase-beta, decreased the degree of insulin resistance by almost 70%. However, aspirin had no effect on the development of hypertension. We conclude that obesity-induced hypertension and obesity-induced insulin resistance are not directly related. In addition, there is a suggestion that insulin resistance in this experimental model is mediated through the central and or peripheral alpha2-adrenoceptors, whereas hypertension is mediated through the alpha1- and or beta-adrenoceptors.

  5. PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity

    NARCIS (Netherlands)

    Jans, A.; Konings, E.; Goossens, G.H.; Bouwman, F.G.; Moors, C.C.; Boekschoten, M.V.; Afman, L.A.; Muller, M.R.; Mariman, E.C.; Blaak, E.E.

    2012-01-01

    Background: Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. Objective: The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial

  6. The role of insulin therapy and glucose normalization in patients with acute coronary syndrome

    NARCIS (Netherlands)

    J.A. Lipton; A. Can; S. Akoudad (Saloua); M.L. Simoons (Maarten)

    2011-01-01

    textabstractPatients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic p

  7. Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes

    Directory of Open Access Journals (Sweden)

    Hsieh Ming-Ju

    2012-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV infection may cause liver diseases of various severities ranging from primary acute infection to life-threatening diseases, such as cirrhosis or hepatocellular carcinoma with poor prognosis. According to clinical findings, HCV infection may also lead to some extra-hepatic symptoms, including type 2 diabetes mellitus (DM. Since insulin resistance is the major etiology for type 2 DM and numerous evidences showed that HCV infection associated with insulin resistance, the involvement of E2 in the pathogenesis of type 2 DM and underlying mechanisms were investigated in this study. Methods Reverse transcription and real-time PCR, Western blot assay, Immunoprecipitation, Glucose uptake assay and analysis of cellular glycogen content. Results Results showed that E2 influenced on protein levels of insulin receptor substrate-1 (IRS-1 and impaired insulin-induced Ser308 phosphorylation of Akt/PKB and Ser9 phosphorylation of GSK3β in Huh7 cells, leading to an inhibition of glucose uptake and glycogen synthesis, respectively, and eventually insulin resistance. Conclusions Therefore, HCV E2 protein indeed involved in the pathogenesis of type 2 DM by inducing insulin resistance.

  8. Severe Injury Is Associated With Insulin Resistance, Endoplasmic Reticulum Stress Response, and Unfolded Protein Response

    Science.gov (United States)

    Jeschke, Marc G.; Finnerty, Celeste C.; Herndon, David N.; Song, Juquan; Boehning, Darren; Tompkins, Ronald G.; Baker, Henry V.; Gauglitz, Gerd G.

    2012-01-01

    Objective We determined whether postburn hyperglycemia and insulin resistance are associated with endoplasmic reticulum (ER) stress/unfolded protein response (UPR) activation leading to impaired insulin receptor signaling. Background Inflammation and cellular stress, hallmarks of severely burned and critically ill patients, have been causally linked to insulin resistance in type 2 diabetes via induction of ER stress and the UPR. Methods Twenty severely burned pediatric patients were compared with 36 nonburned children. Clinical markers, protein, and GeneChip analysis were used to identify transcriptional changes in ER stress and UPR and insulin resistance–related signaling cascades in peripheral blood leukocytes, fat, and muscle at admission and up to 466 days postburn. Results Burn-induced inflammatory and stress responses are accompanied by profound insulin resistance and hyperglycemia. Genomic and protein analysis revealed that burn injury was associated with alterations in the signaling pathways that affect insulin resistance, ER/sarcoplasmic reticulum stress, inflammation, and cell growth/apoptosis up to 466 days postburn. Conclusion Burn-induced insulin resistance is associated with persistent ER/sarcoplasmic reticulum stress/UPR and subsequent suppressed insulin receptor signaling over a prolonged period of time. PMID:22241293

  9. Effect of folic acid on homocysteine and insulin resistance of overweight and obese children and adolescents

    Science.gov (United States)

    Dehkordi, Elham Hashemi; Sedehi, Morteza; Shahraki, Zohre Gholipour; Najafi, Reza

    2016-01-01

    Background: Considering the increasing trend of childhood obesity and subsequent burden of the disease in Iran and other countries and importance of early life intervention for achieving sustained effect on health of children and adolescents, this study aimed to investigate the effect of two different dose of folic acid on homocysteine (Hcy) level and insulin resistance of obese children. Materials and Methods: In this randomized, double-blind controlled clinical trial study, 60 obese and overweight children aged 5–12 years were enrolled. Selected obese children randomly allocated in two interventional (1 mg/day folic acid and 5 mg/day folic acid, for 8 weeks) and one control groups. Biochemical measurements including folic acid, Hcy, insulin and insulin resistance were measured between and within groups before and after trial. Results: In each group, 20 obese children were studied. The three groups were age and sex matched. After folic acid administration, mean of Hcy, insulin resistance and insulin decreased significantly in two groups which folic acid administrated with two different doses (P 0.05). Mean differences for Hcy, insulin resistance and insulin, in two intervention groups were significantly higher than the control group (P 0.05). Conclusion: The findings of current trial showed that folic acid in two studied doses could be a safe and effective supplement for obese children to reduce Hcy level and insulin resistance, which consequently could prevent obesity-related complications including cardiovascular and metabolic disorders. PMID:27274503

  10. Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance.

    Science.gov (United States)

    Chibalin, Alexander V; Leng, Ying; Vieira, Elaine; Krook, Anna; Björnholm, Marie; Long, Yun Chau; Kotova, Olga; Zhong, Zhihui; Sakane, Fumio; Steiler, Tatiana; Nylén, Carolina; Wang, Jianjun; Laakso, Markku; Topham, Matthew K; Gilbert, Marc; Wallberg-Henriksson, Harriet; Zierath, Juleen R

    2008-02-01

    Type 2 (non-insulin-dependent) diabetes mellitus is a progressive metabolic disorder arising from genetic and environmental factors that impair beta cell function and insulin action in peripheral tissues. We identified reduced diacylglycerol kinase delta (DGKdelta) expression and DGK activity in skeletal muscle from type 2 diabetic patients. In diabetic animals, reduced DGKdelta protein and DGK kinase activity were restored upon correction of glycemia. DGKdelta haploinsufficiency increased diacylglycerol content, reduced peripheral insulin sensitivity, insulin signaling, and glucose transport, and led to age-dependent obesity. Metabolic flexibility, evident by the transition between lipid and carbohydrate utilization during fasted and fed conditions, was impaired in DGKdelta haploinsufficient mice. We reveal a previously unrecognized role for DGKdelta in contributing to hyperglycemia-induced peripheral insulin resistance and thereby exacerbating the severity of type 2 diabetes. DGKdelta deficiency causes peripheral insulin resistance and metabolic inflexibility. These defects in glucose and energy homeostasis contribute to mild obesity later in life. PMID:18267070

  11. Beneficial insulin-sensitizing and vascular effects of S15261 in the insulin-resistant JCR:LA-cp rat.

    Science.gov (United States)

    Russell, J C; Ravel, D; Pégorier, J P; Delrat, P; Jochemsen, R; O'Brien, S F; Kelly, S E; Davidge, S T; Brindley, D N

    2000-11-01

    S15261, a compound developed for the oral treatment of type II diabetes, is cleaved by esterases to the fragments Y415 and S15511. The aim was to define the insulin-sensitizing effects of S15261, the cleavage products, and troglitazone and metformin in the JCR:LA-cp rat, an animal model of the obesity/insulin resistance syndrome that exhibits an associated vasculopathy and cardiovascular disease. Treatment of the animals from 8 to 12 weeks of age with S15261 or S15511 resulted in reductions in food intake and body weights, whereas Y415 had no effect. Troglitazone caused a small increase in food intake (P JCR:LA-cp rat. S15261 may thus offer effective treatment for the insulin resistance syndrome and its associated vascular complications.

  12. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice.

    Science.gov (United States)

    Kurauti, Mirian A; Freitas-Dias, Ricardo; Ferreira, Sandra M; Vettorazzi, Jean F; Nardelli, Tarlliza R; Araujo, Hygor N; Santos, Gustavo J; Carneiro, Everardo M; Boschero, Antonio C; Rezende, Luiz F; Costa-Júnior, José M

    2016-01-01

    The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60-70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe.

  13. Association of chronic viral hepatitis B with insulin resistance

    Institute of Scientific and Technical Information of China (English)

    Jeong Gyu Lee; Sangyeoup Lee; Yun Jin Kim; Byung Mann Cho; Joo Sung Park; Hyung Hoi Kim; JaeHun Cheong

    2012-01-01

    AIM:To investigate the relationship between chronic viral hepatitis B (CVHB) and insulin resistance (IR) in Korean adults.METHODS:A total of 7880 adults (3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this study.Subjects diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were rejected,Anthropometry,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all subjects.Homeostasis model assessment (HOMA),quantitative insulin check index (QUICKI),and Mffm index were used for determining insulin sensitivity.Each participant was categorized into a negative,recovery,or CVHB group.To compare variables between groups,a t-test and/or one-way analysis of variance were used.Partial correlation coefficients were computed to present the association between insulin resistance and other variables.Multiple logistic regression analysis was used to assess the independent association between CVHB and IR.RESULTS:The mean age of men and women were 48.9 and 48.6 years,respectively.Subjects in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P =0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P < 0.001 in women)],cystatin C [(0.96 ± 0.15 mg/dL vs 1.02 ± 0.22 mg/dL,P < 0.001 in men),(0.84 ± 0.15 mg/dL vs 0.90 ± 0.16 mg/dL,P < 0.001 in women)],fasting insulin [(5.47 ± 3.38 μU/mL vs 6.12 ± 4.62 μU/mL,P< 0.001 in men),(4.57 ± 2.82 μU/mL vs 5.06 ± 3.10μU/mL,P < 0.001 in women)] and HOMA index [(1.24± 0.86 vs 1.43 ± 1.24,P < 0.001 in men),(1.02 ±0.76 vs 1.13 ± 0.87,P =0.033 in women)] compared to control group.The HOMA index revealed a positive correlation with body mass index (BMI) (r =0.378,P < 0.001),waist circumference (r =0.356,P < 0.001),percent body fat (r =0.296,P < 0.001),systolic blood pressure (r =0.202,P

  14. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans.

    Science.gov (United States)

    McLaughlin, Tracey; Craig, Colleen; Liu, Li-Fen; Perelman, Dalia; Allister, Candice; Spielman, Daniel; Cushman, Samuel W

    2016-05-01

    Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance. PMID:26884438

  15. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage.

    Science.gov (United States)

    Muniyappa, Ranganath; Lee, Sihoon; Chen, Hui; Quon, Michael J

    2008-01-01

    Insulin resistance contributes to the pathophysiology of diabetes and is a hallmark of obesity, metabolic syndrome, and many cardiovascular diseases. Therefore, quantifying insulin sensitivity/resistance in humans and animal models is of great importance for epidemiological studies, clinical and basic science investigations, and eventual use in clinical practice. Direct and indirect methods of varying complexity are currently employed for these purposes. Some methods rely on steady-state analysis of glucose and insulin, whereas others rely on dynamic testing. Each of these methods has distinct advantages and limitations. Thus, optimal choice and employment of a specific method depends on the nature of the studies being performed. Established direct methods for measuring insulin sensitivity in vivo are relatively complex. The hyperinsulinemic euglycemic glucose clamp and the insulin suppression test directly assess insulin-mediated glucose utilization under steady-state conditions that are both labor and time intensive. A slightly less complex indirect method relies on minimal model analysis of a frequently sampled intravenous glucose tolerance test. Finally, simple surrogate indexes for insulin sensitivity/resistance are available (e.g., QUICKI, HOMA, 1/insulin, Matusda index) that are derived from blood insulin and glucose concentrations under fasting conditions (steady state) or after an oral glucose load (dynamic). In particular, the quantitative insulin sensitivity check index (QUICKI) has been validated extensively against the reference standard glucose clamp method. QUICKI is a simple, robust, accurate, reproducible method that appropriately predicts changes in insulin sensitivity after therapeutic interventions as well as the onset of diabetes. In this Frontiers article, we highlight merits, limitations, and appropriate use of current in vivo measures of insulin sensitivity/resistance. PMID:17957034

  16. [Effect of chronic blockade of the opiodergic receptor on insulin resistance in a hyperandrogenic woman].

    Science.gov (United States)

    Sir, T; López, G; Alba, F; Cipriano, A; Candía, M; Castillo, T; Devoto, L

    1994-04-01

    We report a woman with insulin resistance associated with hyperandrogenism and acanthosis nigricans (HAIR-AN syndrome) treated during 30 days with the prolonged action opioid antagonist Naltrexone. During its administration, decreases in basal blood glucose and serum insulin, insulin and glucose response to a glucose load and plasma testosterone were observed. These findings suggest that opioid activity could play a critical role in the physiopathology of hyperinsulinemia in hyperandrogenic women. PMID:7809540

  17. The effect of vitamin D on insulin resistance in patients with type 2 diabetes

    OpenAIRE

    Talaei Afsaneh; Mohamadi Mahnaz; Adgi Zahra

    2013-01-01

    Abstract Introduction Over the past decade, numerous non-skeletal diseases have been reported to be associated with vitamin D deficiency including type2 diabetes mellitus (T2DM). Different studies provide evidence that vitamin D may play a functional role in glucose tolerance through its effects on insulin secretion and insulin sensitivity. This study evaluates the effects of vitamin D supplementation on insulin resistance in T2DM. Method Through a before-after study, 100 patients with T2DM, ...

  18. Adherence to a Low-Fat versus Low-Carbohydrate Diet Differs by Insulin Resistance Status

    OpenAIRE

    McClain, Arianna D.; Otten, Jennifer J.; Hekler, Eric B.; Gardner, Christopher D.

    2012-01-01

    Previous research shows diminished weight loss success in insulin-resistant (IR) women assigned to a low-fat (LF) diet compared to those assigned to a low-carbohydrate (LC) diet. These secondary analyses examined the relationship between insulin-resistance status and dietary adherence to either a LF-diet or LC-diet among 81 free-living, overweight/obese women (age= 41.9±5.7 yrs; BMI= 32.6±3.6 kg/m2). This study found differential adherence by insulin-resistance status only to a LF-diet, not a...

  19. A pharmacokinetic and pharmacodynamic study of pioglitazone in a model of induced insulin resistance in normal horses

    OpenAIRE

    Wearn, Jamie Macquarie

    2010-01-01

    Equine Metabolic Syndrome (EMS) is a unique condition of horses characterized by adiposity, insulin resistance, and an increased risk of laminitis. Reducing insulin resistance may decrease the incidence of laminitis in horses with EMS. Pioglitazone, a thiazolidinedione class of anti-diabetic drug, has proven efficacy in humans with type 2 diabetes, a syndrome of insulin resistance sharing some similarities with EMS. The ability of pioglitazone to influence insulin sensitivity i...

  20. Rac1 signaling is required for insulin-stimulated glucose uptake and is dysregulated in insulin-resistant murine and human skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke; Jensen, Thomas Elbenhardt; Kleinert, Maximilian;

    2013-01-01

    investigated. We hypothesized that Rac1 and its downstream target, p21-activated kinase (PAK), are regulators of insulin-stimulated glucose uptake in mouse and human skeletal muscle, and are dysregulated in insulin resistant states.Muscle specific inducible Rac1 knockout (KO) mice and pharmacological......The actin-cytoskeleton-regulating GTPase Rac1 is required for insulin-stimulated GLUT4 translocation in cultured muscle cells. However, involvement of Rac1 and its downstream signaling in glucose transport in insulin sensitive and insulin resistant mature skeletal muscle has not previously been...

  1. Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations

    Science.gov (United States)

    Huang-Doran, Isabel; Tomlinson, Patsy; Payne, Felicity; Gast, Alexandra; Sleigh, Alison; Bottomley, William; Harris, Julie; Daly, Allan; Rocha, Nuno; Rudge, Simon; Clark, Jonathan; Kwok, Albert; Romeo, Stefano; McCann, Emma; Müksch, Barbara; Dattani, Mehul; Zucchini, Stefano; Wakelam, Michael; Foukas, Lazaros C.; Savage, David B.; Murphy, Rinki; O’Rahilly, Stephen; Semple, Robert K.

    2016-01-01

    Obesity-related insulin resistance is associated with fatty liver, dyslipidemia, and low plasma adiponectin. Insulin resistance due to insulin receptor (INSR) dysfunction is associated with none of these, but when due to dysfunction of the downstream kinase AKT2 phenocopies obesity-related insulin resistance. We report 5 patients with SHORT syndrome and C-terminal mutations in PIK3R1, encoding the p85α/p55α/p50α subunits of PI3K, which act between INSR and AKT in insulin signaling. Four of 5 patients had extreme insulin resistance without dyslipidemia or hepatic steatosis. In 3 of these 4, plasma adiponectin was preserved, as in insulin receptor dysfunction. The fourth patient and her healthy mother had low plasma adiponectin associated with a potentially novel mutation, p.Asp231Ala, in adiponectin itself. Cells studied from one patient with the p.Tyr657X PIK3R1 mutation expressed abundant truncated PIK3R1 products and showed severely reduced insulin-stimulated association of mutant but not WT p85α with IRS1, but normal downstream signaling. In 3T3-L1 preadipocytes, mutant p85α overexpression attenuated insulin-induced AKT phosphorylation and adipocyte differentiation. Thus, PIK3R1 C-terminal mutations impair insulin signaling only in some cellular contexts and produce a subphenotype of insulin resistance resembling INSR dysfunction but unlike AKT2 dysfunction, implicating PI3K in the pathogenesis of key components of the metabolic syndrome. PMID:27766312

  2. Metabolic effects of short-term GLP-1 treatment in insulin resistant heart failure patients

    DEFF Research Database (Denmark)

    Nielsen, Bent Roni Ranghøj; Wiggers, H; Halbirk, M;

    2012-01-01

    protein turnover (p=0.08) but did not cause muscle wasting. No significant changes in circulating levels of insulin, glucagon, free fatty acids or insulin sensitivity were detected.GLP-1 treatment decreased glucose levels and increased glucose tolerance in insulin resistant HF patients with IHD......We studied the metabolic effects of 48-h GLP-1 treatment in insulin resistant heart failure patients.In a randomized placebo-controlled double-blinded cross-over study, 11 non-diabetic HF patients with IHD received 48-h GLP-1 and placebo-infusion. We applied OGTT, hyperinsulinemic clamp, indirect...... calorimetry, forearm, and tracer methods.7 insulin resistant HF (EF 28%±2) patients completed the protocol. GLP-1 decreased plasma glucose levels (p=0.048) and improved glucose tolerance. 4 patients had hypoglycemic events during GLP-1 vs. none during placebo. GLP-1 treatment tended to increase whole body...

  3. Observations on the presence of insulin resistance in patients with essential hypertension and coronary heart disease

    International Nuclear Information System (INIS)

    Objective: To investigate the presence of insulin resistance in patients with essential hypertension (EH) and coronary heart disease (CHD). Methods: Fasting and 2h post oral 75g glucose blood sugar (with oxidase method), insulin and C-peptide (with RIA) levels were examined in 52 patients with EH, 40 patients with CHD and 35 controls. Results: The fasting and 2h post o- ral glucose serum levels of glucose, insulin and C-peptide in the patients were significantly higher than those in the controls (P < 0.01), suggesting presence of impaired glucose tolerance and insulin resistance. Conclusion: Impaired glucose tolerance due to insulin resistance was demonstrated in the studied patients with EH or CHD. (authors)

  4. Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism

    DEFF Research Database (Denmark)

    Macotela, Yazmin; Emanuelli, Brice; Bång, Anneli M;

    2011-01-01

    homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose...... with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest......Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor--leucine--can modify insulin resistance by acting on multiple tissues...

  5. Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Caihong Zhu

    Full Text Available Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer's disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer's disease. In addition, impaired insulin signaling in the Alzheimer's disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis.

  6. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Shou-Kui Xiang

    2012-01-01

    Full Text Available Objective. To investigate the association between serum lipoprotein ratios and insulin resistance in women with polycystic ovarian syndrome (PCOS. Methods. 105 PCOS patients and 109 controls were randomly enrolled in the study. Serum levels of luteinizing hormone (LH, follicle-stimulating hormone (FSH, estradiol (E2, total testosterone (T, fasting glucose (FBG, fasting insulin (FINS, serum triglycerides (TG, total cholesterol (TC, high-density lipoprotein (HDL-C, and low-density lipoprotein (LDL-C levels were checked, and then TG/HDL-C ratio, TC/HDL-C, ratio and LDL-C/HDL-C ratio were calculated. The homeostasis model assessment of insulin resistance (HOMA-IR was used to calculate the insulin resistance. Results. All lipoprotein ratios were significantly higher in PCOS patients as compared to healthy controls (<0.05. TG/HDL-C ratio, TC/HDL-C ratio, and LDL-C/HDL-C ratio were significantly correlated with HOMA-IR (<0.05. The ROC curve demonstrated that TC/HDL-C ratio had higher sensitivity and specificity in diagnosing PCOS with insulin resistance. Conclusion. This study demonstrates that serum lipoprotein ratio significantly correlates with insulin resistance and can be used as the marker of insulin resistance in PCOS patients.

  7. The association between TNF-α and insulin resistance in euglycemic women.

    LENUS (Irish Health Repository)

    Walsh, Jennifer M

    2013-10-01

    Chronic low levels of inflammation have links to obesity, diabetes and insulin resistance. We sought to assess the relationship between cytokine tumor necrosis factor (TNF-α) and insulin resistance in a healthy, euglycemic population. This is a prospective study of 574 non-diabetic mother and infant pairs. Maternal body mass index (BMI), TNF-α, glucose and insulin were measured in early pregnancy and at 28 weeks. Insulin resistance was calculated by HOMA index. At delivery birthweight was recorded and cord blood analysed for fetal C-peptide and TNF-α. In a multivariate model, maternal TNF-α in early pregnancy was predicted by maternal insulin resistance at the same time-point, (β=0.54, p<0.01), and maternal TNF-α at 28 weeks was predicted by maternal insulin resistance in early pregnancy (β=0.24, p<0.01) and at 28 weeks (β=0.39, p<0.01). These results, in a large cohort of healthy, non-diabetic women have shown that insulin resistance, even at levels below those diagnostic of gestational diabetes, is associated with maternal and fetal inflammatory response. These findings have important implications for defining the pathways of fetal programming of later metabolic syndrome and childhood obesity.

  8. The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Yun Zhao

    2015-09-01

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B, which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1, thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several important components of insulin signal pathway. In this study, we identified that PTP1B is modified by O-GlcNAcylation at three O-GlcNAc sites (Ser104, Ser201, and Ser386. Palmitate acid (PA impaired the insulin signaling, indicated by decreased phosphorylation of both serine/threonine-protein kinase B (Akt and glycogen synthase kinase 3 beta (GSK3β following insulin administration, and upregulated PTP1B O-GlcNAcylation in HepG2 cells. Compared with the wild-type, intervention PTP1B O-GlcNAcylation by site-directed gene mutation inhibited PTP1B phosphatase activity, resulted in a higher level of phosphorylated Akt and GSK3β, recovered insulin sensitivity, and improved lipid deposition in HepG2 cells. Taken together, our research showed that O-GlcNAcylation of PTP1B can influence insulin signal transduction by modulating its own phosphatase activity, which participates in the process of hepatic insulin resistance.

  9. Odontella aurita-enriched diet prevents high fat diet-induced liver insulin resistance.

    Science.gov (United States)

    Amine, Hamza; Benomar, Yacir; Haimeur, Adil; Messaouri, Hafida; Meskini, Nadia; Taouis, Mohammed

    2016-01-01

    The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways.

  10. IL-37 protects against obesity-induced inflammation and insulin resistance

    NARCIS (Netherlands)

    Ballak, D.B.; Diepen, van J.A.; Moschen, A.R.; Jansen, H.; Hijmans, A.; Groenhof, G.J.; Leenders, F.; Bufler, P.; Boekschoten, M.V.

    2014-01-01

    Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member ¿IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resista

  11. SOCS-1 deficiency does not prevent diet-induced insulin resistance

    DEFF Research Database (Denmark)

    Emanuelli, Brice; Macotela, Yazmin; Boucher, Jérémie;

    2008-01-01

    of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver. HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests. Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency...

  12. 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...

  13. 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.

  14. Insulin resistance in the NIDDM model Psammomys obesus in the normoglycaemic, normoinsulinaemic state.

    Science.gov (United States)

    Ziv, E; Kalman, R; Hershkop, K; Barash, V; Shafrir, E; Bar-On, H

    1996-11-01

    The desert gerbil Psammomys obesus ("sand rat"), a model of nutritionally induced insulin resistance and non-insulin-dependent diabetes mellitus, was treated after weaning with exogenous insulin implants in the normoglycaemic, normoinsulinaemic state. Albino rats matched for weight and age served as high energy diet adjusted reference animals. Insulin administration, elevating the serum insulin to 6000 pmol/l resulted in only a mild reduction in blood glucose levels in Psammomys, but caused a severe, often fatal hypoglycaemia in the albino rats. The hepatic response to insulin-induced hypoglycaemia in rats involved a significant loss in glycogen and suppression of phosphoenolpyruvate carboxykinase (PEPCK) activity. In Psammomys under similar hyperinsulinaemia no appreciable changes in liver glycogen and PEPCK activity were evident, indicating that blood glucose was replenished by continuing gluconeogenesis. Euglycaemic, hyperinsulinaemic clamp caused a complete shut-down of hepatic glucose production in albino rats. However, in both diabetes-prone and diabetes-resistant Psammomys lines, mean hepatic glucose production was reduced by only 62 to 53% respectively, despite longer lasting and higher levels of hyperinsulinaemia. These results indicate that Psammomys is characterized by muscle and liver insulin resistance prior to diet-induced hyperglycaemia and hyperinsulinaemia. This is assumed to be a species feature of Psammomys, exemplifying a metabolic adjustment to survival in conditions of food scarcity of both animal and human populations. It may reflect a propensity to insulin resistance and hyperglycaemia in population groups exposed to affluent nutrition.

  15. Skeletal muscle salt inducible kinase 1 promotes insulin resistance in obesity

    Directory of Open Access Journals (Sweden)

    Mark Nixon

    2016-01-01

    Conclusions: SIK1 is dispensable for glycemic control on chow diet. SIK1 promotes insulin resistance on high fat diet by a cell-autonomous mechanism in skeletal muscle. Our study establishes SIK1 as a promising therapeutic target to improve skeletal muscle insulin sensitivity in obese individuals without deleterious effects on hepatic glucose production.

  16. Metabolic flexibility in the development of insulin resistance and type 2 diabetes : effects of lifestyle

    NARCIS (Netherlands)

    Corpeleijn, E.; Saris, W. H. M.; Blaak, E. E.

    2009-01-01

    Lipotoxicity in skeletal muscle plays a critical role in the aetiology of insulin resistance and type 2 diabetes mellitus by interference of lipid metabolites with insulin signalling and action. The dynamics of lipid oxidation and fine tuning with fatty acid uptake and intramyocellular triacylglycer

  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 m...

  18. Bcl10 links saturated fat overnutrition with hepatocellular NF-kB activation and insulin resistance

    NARCIS (Netherlands)

    Beek, M.H. van; Oravecz-Wilson, K.I.; Delekta, P.C.; Gu, S.; Li, X.; Jin, X.; Apel, I.J.; Konkle, K.S.; Feng, Y.; Teitelbaum, D.H.; Ruland, J.; McAllister-Lucas, L.M.; Lucas, P.C.

    2012-01-01

    Excess serum free fatty acids (FFAs) are fundamental to the pathogenesis of insulin resistance. With high-fat feeding, FFAs activate NF-kB in target tissues, initiating negative crosstalk with insulin signaling. However, the mechanisms underlying FFA-dependent NF-kB activation remain unclear. Here,

  19. Modulation of Steroidogenic Pathway in Rat Granulosa Cells with Subclinical Cd Exposure and Insulin Resistance: An Impact on Female Fertility

    Directory of Open Access Journals (Sweden)

    Muskaan Belani

    2014-01-01

    Full Text Available Changes in lifestyle lead to insulin resistance (IR in females ultimately predisposing them towards infertility. In addition, cadmium (Cd, an environmental endocrine disruptor, is reported for detrimental effects on granulosa cells, thus leading to ovarian dysfunction. A combination of these factors, lifestyle and environment, seems to play a role in etiology of idiopathic infertility that accounts for 50% amongst the total infertility cases. To address this issue, we made an attempt to investigate the extent of Cd impact on insulin-resistant (IR granulosa cells. We exposed adult female Charles Foster rats to dexamethasone and confirmed IR condition by fasting insulin resistance index (FIRI. On treatment of IR rats with Cd, the preliminary studies demonstrated prolonged estrous cyclicity, decrease in serum estradiol concentrations, abnormal histology of ovary, and increased granulosa cell death. Further gene and protein expression studies of steroidogenic acute regulatory (StAR protein, 17β-hydroxysteroid dehydrogenase (17β-HSD, and cytochrome P450 aromatase (CYP19A1 were performed. Protein expression studies demonstrated significant decrease in treated groups when compared with control. Study revealed that, in spite of the molecular parameters being affected at varied level, overall ovarian physiology is maximally affected in IR and Cd coexposed group, thus mimicking the condition similar to those prevailing in infertile females.

  20. Acute overexpression of lactate dehydrogenase-A perturbs beta-cell mitochondrial metabolism and insulin secretion.

    Science.gov (United States)

    Ainscow, E K; Zhao, C; Rutter, G A

    2000-07-01

    Islet beta-cells express low levels of lactate dehydrogenase and have high glycerol phosphate dehydrogenase activity. To determine whether this configuration favors oxidative glucose metabolism via mitochondria in the beta-cell and is important for beta-cell metabolic signal transduction, we have determined the effects on glucose metabolism and insulin secretion of acute overexpression of the skeletal muscle isoform of lactate dehydrogenase (LDH)-A. Monitored in single MIN6 beta-cells, LDH hyperexpression (achieved by intranuclear cDNA microinjection or adenoviral infection) diminished the response to glucose of both phases of increases in mitochondrial NAD(P)H, as well as increases in mitochondrial membrane potential, cytosolic free ATP, and cystolic free Ca2+. These effects were observed at all glucose concentrations, but were most pronounced at submaximal glucose levels. Correspondingly, adenoviral vector-mediated LDH-A overexpression reduced insulin secretion stimulated by 11 mmol/l glucose and the subsequent response to stimulation with 30 mmol/l glucose, but it was without significant effect when the concentration of glucose was raised acutely from 3 to 30 mmol/l. Thus, overexpression of LDH activity interferes with normal glucose metabolism and insulin secretion in the islet beta-cell type, and it may therefore be directly responsible for insulin secretory defects in some forms of type 2 diabetes. The results also reinforce the view that glucose-derived pyruvate metabolism in the mitochondrion is critical for glucose-stimulated insulin secretion in the beta-cell.

  1. S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

    International Nuclear Information System (INIS)

    Research highlights: →Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. →Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. →Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. →Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia (∼18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPARγ) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 ± 16.32 vs. 126.37 ± 27.07 mg/dl) and glucose intolerance (∼78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.

  2. S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vikram, Ajit [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India); Jena, Gopabandhu, E-mail: gbjena@gmail.com [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India)

    2010-07-23

    Research highlights: {yields}Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. {yields}Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. {yields}Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. {yields}Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia ({approx}18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPAR{gamma}) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 {+-} 16.32 vs. 126.37 {+-} 27.07 mg/dl) and glucose intolerance ({approx}78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.

  3. Association between smoking,pancreatic insulin secretion and insulin resistance in Chinese subjects with or without glucose intolerance

    Institute of Scientific and Technical Information of China (English)

    KO Gary Tin-Choi; TONG Peter Chun-Yip; SO Wing-Yee; COCKRAM Clive S; CHAN Juliana Chung-Ngor

    2007-01-01

    Background There are studies suggesting smoking may increase the risk of type 2 diabetes.Effects of smoking on insulin secretion and insulin resistance(IR)are,however,controversial.Methods This is a cross-sectional study.Since there were very few smokers among Hong Kong Chinese women,only men(n=1068) were analyzed in this report.Fasting and 2-hour plasma glucose and insulin were measured.Insulinogenic index as well as beta-cell function and IR based on homeostatic model assessment(HOMA)by computer model(HOMA Calculator v2.2)were calculated.Results Of the 1068 men,147 had newly diagnosed diabetes,131 newly diagnosed impaired glucose tolerance(IGT) and 790 were non-diabetic normal controls.Smokers had similar fasting and 2-hour insulin levels,insulinogenic index and HOMA derived beta-cell function as compared to non-smokers in the groups with diabetes,IGT or normal oral glucose tolerance test(OGTT).IR was also similar between smokers,ex-smokers and non-smokers in those with normal OGTT.In men with IGT or diabetes,after adjustment for age and body mass index,smokers were more insulin resistant as compared to non-smokers(IR,IGT: 1.59±1.07 vs 1.03±0.54,P<0.05;diabetes:1.96±1.36 vs 1.06±0.45,P<0.01).With Logistic regression analysis,comparing smokers and non-smokers,IR was independently associated with smoking(odds ratio(95% CI),IGT: 2.23(1.05,4.71);diabetes:3.92(1.22,12.58)).None of the other insulin parameters enter into the model among those with normal OGTT or comparing ex-smokers and non-smoker or smokers and ex-smokers.Conclusions In Chinese men,smoking did not show any direct association with insulin levels and pancreatic insulin secretion.Smoking men with IGT or diabetes appeared more insulin resistant than their non-smoking counterparts.

  4. A small amount of dietary carbohydrate can promote the HFD-induced insulin resistance to a maximal level.

    Directory of Open Access Journals (Sweden)

    Shuang Mei

    Full Text Available Both dietary fat and carbohydrates (Carbs may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD or HFD containing 0.1-25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1% induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level.

  5. Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers - RESIST. A randomised control trial investigating the effects of two different diets on insulin sensitivity in young people with insulin resistance and/or pre-diabetes.

    OpenAIRE

    Sukanya; Parker Robert; Broderick Carolyn R; Chisholm Kerryn; Burrell Susie; Woodhead Helen J; Steinbeck Katharine; Noakes Manny; Baur Louise A; Garnett Sarah P; Shrinivasan Shubha; Hopley Lori; Hendrie Gilly; Ambler Geoffrey R; Kohn Michael R

    2010-01-01

    Abstract Background Concomitant with the rise in childhood obesity there has been a significant increase in the number of adolescents with clinical features of insulin resistance and prediabetes. Clinical insulin resistance and prediabetes are likely to progress to type 2 diabetes and early atherosclerosis if not targeted for early intervention. There are no efficacy trials of lifestyle intervention in this group to inform clinical practice. The primary aim of this randomised control trial (R...

  6. Role of insulin resistance and diet in acne

    OpenAIRE

    Rashmi Kumari; Devinder Mohan Thappa

    2013-01-01

    There is increasing evidence in support of the interplay of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signaling during puberty, which have a causal role in pathogenesis of acne by influencing adrenal and gonadal androgen metabolism. Milk consumption and hyperglycemic diets can induce insulin and IGF-1-mediated PI3K ⁄ Akt-activation inducing sebaceous lipogenesis, sebocyte, and keratinocyte proliferation, which can aggravate acne. Occurence of acne as part of vario...

  7. Effect of acute endurance and resistance exercise on endocrine hormones directly related to lipolysis and skeletal muscle protein synthesis in adult individuals with obesity.

    Science.gov (United States)

    Hansen, Dominique; Meeusen, Romain; Mullens, Annelies; Dendale, Paul

    2012-05-01

    In subjects with obesity, the implementation of long-term exercise intervention increases lean tissue mass and lowers adipose tissue mass. However, data indicate a blunted lipolytic response, and/or skeletal muscle protein synthesis, when subjects with obesity are exposed to acute endurance or resistance exercise, respectively. Therefore, subjects with obesity seem to display a suboptimal physiological response to acute exercise stimuli. It might be hypothesized that hormonal disturbances contribute, at least in part, to these abnormal physiological reactions in the obese. This review discusses the impact of acute endurance and resistance exercise on endocrine hormones directly related to lipolysis and/or skeletal muscle protein synthesis (insulin, [nor]epinephrine, cortisol, growth hormone, testosterone, triiodothyronine, atrial natriuretic peptide, insulin-like growth factor-1), as well as the impact of long-term endurance and resistance exercise intervention on these hormonal responses to acute endurance and resistance exercise. In the obese, some endocrinological disturbances during acute endurance and resistance exercise have been identified: a blunted blood growth hormone, atrial natriuretic peptide and epinephrine release, and greater cortisol and insulin release. These hormonal disturbances might contribute to a suppressed lipolytic response, and/or suppressed skeletal muscle protein synthesis, as a result of acute endurance or resistance exercise, respectively. In subjects with obesity, the impact of acute endurance and resistance exercise on other endocrine hormones (norepinephrine, testosterone, triiodothyronine, insulin-like growth factor-1) remains elusive. Furthermore, whether long-term endurance and resistance exercise intervention might reverse these hormonal disturbances during acute endurance and resistance exercise in these individuals remains unknown.

  8. Body mass index a better predictor of insulin resistance than waist circumference in normoglycemics

    Directory of Open Access Journals (Sweden)

    B.L. Preethi

    2015-04-01

    Full Text Available Background: Body Mass Index (BMI is the most common method of measuring obesity. Many studies have reported that waist circumference is a stronger predictor of insulin resistance in non-type 2 diabetes. The objective of the study was to investigate whether waist circumference (WC or body mass index (BMI is a better predictor insulin resistance. Method: 79 normal young adult volunteers in the age range of 18 to 25 years were enrolled for the Study. All subjects underwent a detailed general physical examination including Blood Pressure, body weight, height, hip & waist circumference. BMI (Body Mass Index, waist and hip circumference & waist hip ratio calculated. 2hr OGTT with serum Insulin was performed and Insulin resistance calculated. Result: Simple clinical measures of obesity like height, weight, waist circumference, hip circumference and their indexes like BMI (body mass index, WHR (waist hip ratio were evaluated and correlated with the measures of Insulin resistance (IR and insulin sensitivity. BMI was found to significantly correlate with most of the IR parameters and there was a trend towards significance with weight. Waist circumference did not correlate significantly with IR parameters. Conclusion: Body Mass Index (BMI is a useful tool in evaluating obesity in normoglycemic subjects. BMI is a better predictor of Insulin Resistance and risk stratification than waist circumference.

  9. Insulin, pioglitazone and Zingiber officinale administrations improve proliferating cell nuclear antigen immunostaining effects on diabetic and insulin resistant rat testis

    OpenAIRE

    DARAMOLA, Adetola Olubunmi; OLATUNJI-BELLO, Ibiyemi Ibitola; OBIKA, Leonard Fidelis

    2013-01-01

    This study accessed the effects of hypoglycaemic drugs on spermatogenesis in diabetic and insulin resistant rat testis following proliferating cell nuclear antigen (PCNA) immunostaining. Male adult Sprague-Dawley rats (120-140 g) were randomly divided into 5 groups. Group 1 served as control group; fed on normal rat pellets. Group 2 served as streptozotocin-insulin treated group; received a single dose IP Injection of streptozotocin 45 mg/kg BW in Na+ citrate buffer pH 4.5 and treated with in...

  10. Obesity-related insulin resistance: implications for the surgical patient.

    Science.gov (United States)

    Tewari, N; Awad, S; Macdonald, I A; Lobo, D N

    2015-11-01

    In healthy surgical patients, preoperative fasting and major surgery induce development of insulin resistance (IR). IR can be present in up to 41% of obese patients without diabetes and this can rise in the postoperative period, leading to an increased risk of postoperative complications. Inflammation is implicated in the aetiology of IR. This review examines obesity-associated IR and its implications for the surgical patient. Searches of the Medline and Science Citation Index databases were performed using various key words in combinations with the Boolean operators AND, OR and NOT. Key journals, nutrition and metabolism textbooks and the reference lists of key articles were also hand searched. Adipose tissue has been identified as an active endocrine organ and the chemokines secreted as a result of macrophage infiltration have a role in the pathogenesis of IR. Visceral adipose tissue appears to be the most metabolically active, although results across studies are not consistent. Results from animal and human studies often provide conflicting results, which has rendered the pursuit of a common mechanistic pathway challenging. Obesity-associated IR appears, in part, to be related to inflammatory changes associated with increased adiposity. Postoperatively, the surgical patient is in a proinflammatory state, so this finding has important implications for the obese surgical patient. PMID:26028059

  11. Human obesity and insulin resistance: lessons from experiments of nature.

    Science.gov (United States)

    O'Rahilly, Stephen

    2007-01-01

    The past decade or so has seen the adipocyte catapulted from a position of relative obscurity onto the centre stage of biomedical science. Having long been viewed largely as a passive storage depot for energy in times of plenty and a fuel reservoir called upon in times of need, the discovery that the adipocyte is an active participant in the control mechanisms for both energy balance and intermediary metabolism represents one of the most stunning paradigm shifts in modern mammalian biology. The normal control of energy homeostasis is now known to be highly dependent on the adipocyte-secreted hormone, leptin. Defects in the leptin signalling pathway, both inherited and acquired, are now known to contribute to the important clinical problem of obesity. Dysfunction of adipocytes, in both obesity and lipodystrophies, is now considered to be critically involved in the pathogenesis of insulin resistance, the metabolic syndrome and type 2 diabetes. The range of metabolites, steroids and bioactive peptides now known to be actively produced by adipocytes and influencing organs as diverse as brain, muscle, liver and pancreatic islet has increased dramatically. Our understanding of how these are co-ordinated to regulate normal metabolism and are dysregulated in metabolic disease is still in its infancy. However what is clear is that the adipocyte, until recently the 'Cinderella Cell' of metabolism, has rapidly become the 'Belle of the Ball'. PMID:18269171

  12. Effect of Omega-3 Fatty Acids Treatment on Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Mogoş Tiberius

    2014-12-01

    Full Text Available Background and aims: Insulin resistance (IR is a common pathogenic factor of several diseases: diabetes mellitus, the metabolic syndrome, arterial hypertension, atherosclerosis, dyslipidemia, etc. There are many therapeutic factors involved in decreasing IR. Among them we mention metformin, pioglitazone, physical activity, weight loss, diet, etc. In the last decade, there are more observations of the influence of polyunsaturated fatty acids on IR. The most powerful seem to be omega-3 fatty acids. In our study, we wanted to asses if the administration of omega-3 fatty acids is involved in modifying IR. Materials and methods: We evaluated 126 diabetic patients with IR from January 2011 until July 2014. The study was open-label and non-randomized. For the determination of IR we used the HOMA-IR method. Results: For both males and females there was a regression of HOMA-IR during the 4 weeks of treatment with omega-3 and also after 2 weeks after stopping the administration of these fatty acids. The decrease of HOMA-IR was statistically significant (p<0.05. The statistic result observed in the next 2 weeks after stopping administration of omega-3 was also significant (p<0.05.

  13. Polymorphisms of Exon 17 of Insulin-Receptor Gene in Pathogenesis of Human Disorders With Insulin Resistance

    Institute of Scientific and Technical Information of China (English)

    LU WANG; JIE MI; XIAO-YUAN ZHAO; JIAN-XIN WU; HONG CHENG; ZHI-KUN ZHANG; XIU-YUAN DING; DONG-QING HOU; HUILI

    2004-01-01

    To investigate the relationship between polymorphisms of insulin-receptor (INSR) gene and insulin resistance in a population-based study in China. Methods Polymerase Chain Reaction (PCR) was used to the amplify Exon 17 of INSR gene and all amplified products were analyzed by direct sequencing. Results Six single-nucleotide polymorphisms (SNPs) were found at the following loci: T to TC at the locus of 10699 (Tyr984), G to GC at the locus of 10731 (Glu994), Deletion G at the locus of 10798 (Asp1017), C to T/TC at the locus of 10923 (His1058), C to CA at the locus of 10954 (Leu1069), and T to TA at the locus of 10961 (Phe1071), which might not change the amino acid sequence. The data were in agreement with the test of Hardy-Weinberg balance (P>0.05). Among the 345 cases, all clinical indices were higher in males than in females except for HDL cholesterol (P0.05). After sex stratification in analysis,all allele frequencies on the six loci of SNPs of Exon 17 had different distributions between the insulin resistant group and the control group, but P>0.05. Conclusion SNPs of Exon 17 of INSR gene are unlikely to play a direct role in the pathogenesis of human disorders with insulin resistance.

  14. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance.

    Science.gov (United States)

    Holland, William L; Brozinick, Joseph T; Wang, Li-Ping; Hawkins, Eric D; Sargent, Katherine M; Liu, Yanqi; Narra, Krishna; Hoehn, Kyle L; Knotts, Trina A; Siesky, Angela; Nelson, Don H; Karathanasis, Sotirios K; Fontenot, Greg K; Birnbaum, Morris J; Summers, Scott A

    2007-03-01

    Insulin resistance occurs in 20%-25% of the human population, and the condition is a chief component of type 2 diabetes mellitus and a risk factor for cardiovascular disease and certain forms of cancer. Herein, we demonstrate that the sphingolipid ceramide is a common molecular intermediate linking several different pathological metabolic stresses (i.e., glucocorticoids and saturated fats, but not unsaturated fats) to the induction of insulin resistance. Moreover, inhibition of ceramide synthesis markedly improves glucose tolerance and prevents the onset of frank diabetes in obese rodents. Collectively, these data have two important implications. First, they indicate that different fatty acids induce insulin resistance by distinct mechanisms discerned by their reliance on sphingolipid synthesis. Second, they identify enzymes required for ceramide synthesis as therapeutic targets for combating insulin resistance caused by nutrient excess or glucocorticoid therapy.

  15. Insulin Resistance and Endothelial Dysfunction Constitute a Common Therapeutic Target in Cardiometabolic Disorders

    Directory of Open Access Journals (Sweden)

    A. Janus

    2016-01-01

    Full Text Available Insulin resistance and other risk factors for atherosclerosis, such as hypertension and hypercholesterolemia, promote endothelial dysfunction and lead to development of metabolic syndrome which constitutes an introduction to cardiovascular disease. The insulin resistance and endothelial dysfunction cross talk between each other by numerous metabolic pathways. Hence, targeting one of these pathologies with pleiotropic treatment exerts beneficial effect on another one. Combined and expletive treatment of hypertension, lipid disorders, and insulin resistance with nonpharmacological interventions and conventional pharmacotherapy may inhibit the transformation of metabolic disturbances to fully developed cardiovascular disease. This paper summarises the common therapeutic targets for insulin resistance, endothelial dysfunction, and vascular inflammatory reaction at molecular level and analyses the potential pleiotropic effects of drugs used currently in management of cardiovascular disease, metabolic syndrome, and diabetes.

  16. Triiodothyronine : a link between the insulin resistance syndrome and blood pressure?

    NARCIS (Netherlands)

    Bakker, SJL; ter Maaten, JC; Popp-Snijders, C; Heine, RJ; Gans, ROB

    1999-01-01

    Objective Overall obesity is associated with elevated serum triiodothyronine concentrations and insulin resistance. Oral triiodothyronine is known to induce hypertension in laboratory rats, while triiodothyronine also increases the expression of genes encoding for enzymes involved in the synthesis a

  17. Stressful life events are associated with insulin resistance among Chinese immigrant women in the United States

    Directory of Open Access Journals (Sweden)

    Carolyn Y. Fang

    2015-01-01

    Conclusions: This is one of the first studies to examine the associations between psychosocial stress and insulin resistance in Chinese immigrant women. These findings contribute to a growing body of literature on stress and diabetes risk in an immigrant population.

  18. The role of PTEN in chronic growth hormone-induced hepatic insulin resistance.

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    Full Text Available Chronic growth hormone (GH therapy has been shown to cause insulin resistance, but the mechanism remains unknown. PTEN, a tumor suppressor gene, is a major negative regulator of insulin signaling. In this study, we explored the effect of chronic GH on insulin signaling in the context of PTEN function. Balb/c healthy mice were given recombinant human or bovine GH intraperitoneally for 3 weeks. We found that phosphorylation of Akt was significantly decreased in chronic GH group and the expression of PTEN was significantly increased. We further examined this effect in the streptozotocin-induced Type I diabetic mouse model, in which endogenous insulin secretion was disrupted. Insulin/PI3K/Akt signaling was impaired. However, different from the observation in healthy mice, the expression of PTEN did not increase. Similarly, PTEN expression did not significantly increase in chronic GH-treated mice with hypoinsulinemia induced by prolonged fasting. We conducted in-vitro experiments in HepG2 cells to validate our in-vivo findings. Long-term exposure to GH caused similar resistance of insulin/PI3K/Akt signaling in HepG2 cells; and over-expression of PTEN enhanced the impairment of insulin signaling. On the other hand, disabling the PTEN gene by transfecting the mutant PTEN construct C124S or siPTEN, disrupted the chronic GH induced insulin resistance. Our data demonstrate that PTEN plays an important role in chronic-GH-induced insulin resistance. These findings may have implication in other pathological insulin resistance.

  19. Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance

    Science.gov (United States)

    Hoeks, Joris; van Herpen, Noud A.; Mensink, Marco; Moonen-Kornips, Esther; van Beurden, Denis; Hesselink, Matthijs K.C.; Schrauwen, Patrick

    2010-01-01

    OBJECTIVE Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we employed the unique model of prolonged fasting in humans. Prolonged fasting is a physiologic condition in which muscular insulin resistance develops in the presence of increased free fatty acid (FFA) levels, increased fat oxidation and low glucose and insulin levels. It is therefore anticipated that skeletal muscle mitochondrial function is maintained to accommodate increased fat oxidation unless factors secondary to insulin resistance exert negative effects on mitochondrial function. RESEARCH DESIGN AND METHODS While in a respiration chamber, twelve healthy males were subjected to a 60 h fast and a 60 h normal fed condition in a randomized crossover design. Afterward, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, and mitochondrial function was quantified ex vivo in permeabilized muscle fibers using high-resolution respirometry. RESULTS Indeed, FFA levels were increased approximately ninefold after 60 h of fasting in healthy male subjects, leading to elevated intramuscular lipid levels and decreased muscular insulin sensitivity. Despite an increase in whole-body fat oxidation, we observed an overall reduction in both coupled state 3 respiration and maximally uncoupled respiration in permeabilized skeletal muscle fibers, which could not be explained by changes in mitochondrial density. CONCLUSIONS These findings confirm that the insulin-resistant state has secondary negative effects on mitochondrial function. Given the low insulin and glucose levels after prolonged fasting, hyperglycemia and insulin action per se can be excluded as underlying mechanisms, pointing toward elevated plasma FFA and/or intramuscular fat accumulation as possible

  20. How does acupuncture affect insulin sensitivity in women with polycystic ovary syndrome and insulin resistance? Study protocol of a prospective pilot study

    OpenAIRE

    Zheng, Yanhua; Stener-Victorin, Elisabet; Ng, Ernest H. Y.; Li, Juan; Wu, Xiaoke; Ma, Hongxia

    2015-01-01

    Introduction Hyperinsulinaemia and insulin resistance (IR) are key features of polycystic ovary syndrome (PCOS) and metabolic syndrome. The effect of 5 weeks of acupuncture treatment has been investigated in a completed prospective pilot trial (Clinicaltrials.gov: NCT01457209), and acupuncture with electrical stimulation applied to insulin-resistant rats with dihydrotestosterone-induced PCOS was shown to improve insulin sensitivity. Therefore, we now aim to conduct a prospective pilot study t...

  1. Effect of Opuntia humifusa Supplementation and Acute Exercise on Insulin Sensitivity and Associations with PPAR-γ and PGC-1α Protein Expression in Skeletal Muscle of Rats

    Directory of Open Access Journals (Sweden)

    Youngju Song

    2013-03-01

    Full Text Available This study examined whether Opuntia humifusa (O. humifusa, which is a member of the Cactaceae family, supplementation and acute swimming exercise affect insulin sensitivity and associations with PPAR-γ and PGC-1α protein expression in rats. Thirty-two rats were randomly divided into four groups (HS: high fat diet sedentary group, n = 8; HE: high fat diet acute exercise group, n = 8; OS: 5% O. humifusa supplemented high fat diet sedentary group, n = 8; OE: 5% O. humifusa supplemented high fat diet acute exercise group, n = 8. Rats in the HE and OE swam for 120 min. before being sacrificed. Our results indicated that serum glucose level, fasting insulin level and homeostasis model assessment of insulin resistance (HOMA-IR in OS were significantly lower compared to those of the HS (p < 0.01, p < 0.05, p < 0.05. In addition, PPAR-γ protein expression in the OS and OE was significantly higher than that of the HS and HE, respectively (p < 0.05, p < 0.01. PGC-1α and GLUT-4 protein expressions in the OS were significantly higher compared to those of the HS (p < 0.05, p < 0.05. From these results, O. humifusa supplementation might play an important role for improving insulin sensitivity through elevation of PPAR-γ, PGC-1α, and GLUT-4 protein expression in rat skeletal muscle.

  2. Effect of Vitamin K Supplementation on Insulin Resistance in Older Men and Women

    OpenAIRE

    Yoshida, Makiko; Jacques, Paul F.; Saltzman, Edward; Gundberg, Caren; Dawson-Hughes, Bess; Dallal, Gerard; Booth, Sarah L.; Meigs, James Benjamin; Shea, M. Kyla

    2008-01-01

    Objective: Vitamin K has a potentially beneficial role in insulin resistance, but evidence is limited in humans. We tested the hypothesis that vitamin K supplementation for 36 months will improve insulin resistance in older men and women. Research Design and Methods: This was an ancillary study of a 36-month, randomized, double-blind, controlled trial designed to assess the impact of supplementation with 500 μg/day phylloquinone on bone loss. Study participants were older nondiabetic men and ...

  3. Association between Serum Leptin Concentrations and Insulin Resistance: A Population-Based Study from China

    OpenAIRE

    Hui Zuo; Zumin Shi; Baojun Yuan; Yue Dai; Gaolin Wu; Akhtar Hussain

    2013-01-01

    BACKGROUND: Insulin resistance contributes to the cardio-metabolic risk. The effect of leptin in obese and overweight population on insulin resistance was seldom reported. METHODS: A total of 1234 subjects (572 men and 662 women) aged ≥18 y was sampled by the procedure. Adiposity measures included BMI, waist circumference, hip circumference, WHR, upper arm circumference, triceps skinfold and body fat percentage. Serum leptin concentrations were measured by an ELISA method. The homeostasis mod...

  4. Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity

    OpenAIRE

    Zhu, Lin; Martinez, Melissa N.; Emfinger, Christopher H.; Palmisano, Brian T.; John M Stafford

    2014-01-01

    The development of insulin resistance in the liver is a key event that drives dyslipidemia and predicts diabetes and cardiovascular risk with obesity. Clinical data show that estrogen signaling in males helps prevent adiposity and insulin resistance, which may be mediated through estrogen receptor-α (ERα). The tissues and pathways that mediate the benefits of estrogen signaling in males with obesity are not well defined. In female mice, ERα signaling in the liver helps to correct pathway-sele...

  5. Fitness versus Fatness and Insulin Resistance in U.S. Adolescents

    OpenAIRE

    Cummings, Doyle M; DuBose, Katrina D.; Satomi Imai; Collier, David N.

    2010-01-01

    Background. The present study examined the relationship between insulin resistance and both waist circumference and cardiorespiratory fitness in U.S. adolescents. Methods. NHANES assessed a nationally representative sample of U.S. adolescents (12–18 yrs) between 1999–2002. Abdominal adiposity was estimated by waist circumference, overall adiposity by BMI, and cardiorespiratory fitness (maximal oxygen uptake (VO2max) from a treadmill exercise test). Insulin resistance was estimated from fastin...

  6. Serum Autotaxin/ENPP2 Correlates with Insulin Resistance in Older Humans with Obesity

    OpenAIRE

    Reeves, Valerie L.; Trybula, Joy S.; Wills, Rachel C.; Goodpaster, Bret H.; Dubé, John J.; Kienesberger, Petra C; Kershaw, Erin E.

    2015-01-01

    Objective Autotaxin (ATX) is an adipocyte-derived lysophospholipase D that generates the lipid signaling molecule lysophosphatidic acid (LPA). The ATX/LPA pathway in adipose tissue has recently been implicated in obesity and insulin resistance in animal models, but the role of circulating ATX in humans remains unclear. The aim of the present study was to determine the relationship between serum ATX and insulin resistance. Methods In this retrospective study, older (60–75 years), non-diabetic ...

  7. INFLUENCE OF HERBAL EXTRACTS ON METABOLIC DISTURBANCES IN DIABETES MELLITUS AND INSULIN RESISTANCE MODEL

    OpenAIRE

    T. V. Yakimova; O. N. Nasanova; A. I. Vengerovsky

    2015-01-01

    The aim of this research was to assess the influence on metabolic processes of herbal extracts, used in diets with different fat content, in diabetes mellitus and insulin resistance model.Material and methods. The experiments were performing on 90 noninbred male albino rats. Diabetes mellitus was modeling with twice-repeated intraperitoneal streptozotocine (30 mg/kg) injections. For the insulin resistance formation animals were fad meal with 30% fat content. Against the background rats were a...

  8. Angiotensin II Receptor Blocker Ameliorates Stress-Induced Adipose Tissue Inflammation and Insulin Resistance

    OpenAIRE

    Motoharu Hayashi; Kyosuke Takeshita; Yasuhiro Uchida; Koji Yamamoto; Ryosuke Kikuchi; Takayuki Nakayama; Emiko Nomura; Xian Wu Cheng; Tadashi Matsushita; Shigeo Nakamura; Toyoaki Murohara

    2014-01-01

    A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restra...

  9. On the importance of fat cell size, location and signaling in insulin resistance

    OpenAIRE

    Franck, Niclas

    2009-01-01

    Obesity has reached epidemic proportions worldwide and is associated with insulin resistance, type 2 diabetes and cardiovascular disease. During the past decades, substantial evidence has demonstrated that not only the amount of adipose tissue constitutes a major determinant in the development of metabolic disorders, but also the distribution. The visceral adipose tissue has shown to be stronger correlated with insulin resistance, type 2 diabetes and cardiovascular disease than the subcutaneo...

  10. Decreased Skin-Mediated Detoxification Contributes to Oxidative Stress and Insulin Resistance

    OpenAIRE

    Xing-Xing Liu; Chang-Bin Sun; Ting-Tong Yang; Da Li; Chun-Yan Li; Yan-Jie Tian; Ming Guo; Yu Cao; Shi-Sheng Zhou

    2012-01-01

    The skin, the body's largest organ, plays an important role in the biotransformation/detoxification and elimination of xenobiotics and endogenous toxic substances, but its role in oxidative stress and insulin resistance is unclear. We investigated the relationship between skin detoxification and oxidative stress/insulin resistance by examining burn-induced changes in nicotinamide degradation. Rats were divided into four groups: sham-operated, sham-nicotinamide, burn, and burn-nicotinamide. Ra...

  11. Adiponectin is associated with risk of the metabolic syndrome and insulin resistance in women

    OpenAIRE

    King, George A.; Deemer, Sarah E.; Thompson, Dixie L

    2010-01-01

    The purpose of this study was to examine insulin resistance, markers of the metabolic syndrome, cardiovascular disease (CVD) risk, and serum adiponectin concentrations in pre-menopausal Hispanic and non-Hispanic White (NHW) women. This cross-sectional study examined 119 pre-menopausal women (76 Hispanic, 45 NHW) for markers of the metabolic syndrome (ATP III criteria), level of insulin resistance (HOMA-IR), CVD risk factors, and serum total adiponectin concentrations. Relationships between va...

  12. Microbial Translocation in HIV Infection is Associated with Dyslipidemia, Insulin Resistance, and Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    Pedersen, Karin Kaereby; Pedersen, Maria; Trøseid, Marius;

    2013-01-01

    Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals.......Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals....

  13. Blood Mercury and Insulin Resistance in Nondiabetic Koreans (KNHANES 2008-2010)

    OpenAIRE

    Kim, Kyu-Nam; Park, Soo-Jung; Choi, Beomhee; Joo, Nam-Seok

    2015-01-01

    Purpose Blood mercury levels are associated with inflammation, and chronic low-grade inflammation is a cause of insulin resistance. This study aimed to investigate the association between serum mercury and insulin resistance. Materials and Methods Subjects from the 2008-2010 Korean National Health and Nutrition Examination Survey were selected (n=29235) and the relevant data of 5388 subjects (2643 males and 2745 females) were analyzed cross-sectionally. Homeostasis Model Assessment for Insuli...

  14. Mechanisms Linking the Metabolic Syndrome and Cardiovascular Disease: Role of Hepatic Insulin Resistance

    OpenAIRE

    Khosrow Adeli; Reza Meshkani

    2009-01-01

    The worldwide prevalence of insulin resistant states such as the metabolic syndrome has grown rapidly over the past few decades. The metabolic syndrome is a constellation of common metabolic disorders that promote the development of atherosclerosis and cardiovascular disease. Studies in both human and animal models suggest that hepatic inflammation and insulin resistance are key initiating factors in the development of the metabolic syndrome. Chronic inflammation is known to be associated wit...

  15. Oxidative Stress: A Potential Recipe For Anxiety, Hypertension and Insulin Resistance

    OpenAIRE

    Salim, Samina; Asghar, Mohammad; Chugh, Gaurav; Taneja, Manish; Xia, Zhilian; Saha, Kaustav

    2010-01-01

    We recently reported involvement of oxidative stress in anxiety-like behavior of rats. Others in separate studies have demonstrated a link between oxidative stress and hypertension as well as with type 2 diabetes/insulin resistance. In the present study, we have tested a putative role of oxidative stress in anxiety-like behavior, hypertension and insulin resistance using a rat model of oxidative stress. Oxidative stress in rats was produced by xanthine (0.1%; drinking water) and xanthine oxid...

  16. Insulin Resistance Is an Important Risk Factor for Cognitive Impairment in Elderly Patients with Primary Hypertension

    OpenAIRE

    Ma, Lina; Feng, Ming; Qian, Yuying; YANG Wei; Liu, Jia; Han, Rui; Zhu, Hong; Li, Yun

    2014-01-01

    Purpose Insulin resistance plays a role in the development of dementia and hypertension. We investigated a possible relationship between cognitive impairment and insulin resistance in elderly Chinese patients with primary hypertension. Materials and Methods One hundred and thirty-two hypertensive elderly patients (>60 years) were enrolled in this study, and assigned into either the cognitive impairment group (n=61) or the normal cognitive group (n=71). Gender, age, education, body mass index ...

  17. Dietary glycemic index, glycemic load, fiber, simple sugars, and insulin resistance

    DEFF Research Database (Denmark)

    Lau, Cathrine; Faerch, Kristine; Glümer, Charlotte;

    2005-01-01

    To examine the relationship between daily glycemic index, daily glycemic load, simple sugars, dietary fiber, and the prevalence of a measure of insulin resistance in 30- to 60-year-old nondiabetic Danish men and women.......To examine the relationship between daily glycemic index, daily glycemic load, simple sugars, dietary fiber, and the prevalence of a measure of insulin resistance in 30- to 60-year-old nondiabetic Danish men and women....

  18. Resistin induces insulin resistance, but does not affect glucose output in rat-derived hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Feng LIU; Xiao-qing PAN; Mei GUO; Rong-hua CHEN; Xi-rong GUO; Tao YANG; Bin WANG; Min ZHANG; Nan GU; Jie QIU; Hong-qi FAN; Chun-mei ZHANG; Li FEI

    2008-01-01

    Aim: The aim of the present study was to observe the effects of resistin on insulin sensitivity and glucose output in rat-derived hepatocytes. Methods: The rat hepatoma cell line H4IIE was cultured and stimulated with resistin; supernant glucose and glycogen content were detected. The insulin receptor substrate (IRS)-1 and IRS-2, protein kinase B/Akt, glycogen synthase kinase-3β (GSK-3β), the suppressor of cytokine signaling 3 (SOCS-3) protein content, as well as the phosphorylation status were assessed by Western blotting. Specific antisense oligodeoxynucleotides directed against SOCS-3 were used to knockdown SOCS-3. Results: Resistin induced insulin resistance, but did not affect glucose output in rat hepatoma cell line H4IIE. Resistin attenuated multiple effects of insulin, including insulin-stimulated glycogen synthesis and phosphorylation of IRS, pro-tein kinase B/Akt, as well as GSK-3β. Resistin treatment markedly induced the gene and protein expression of SOCS-3, a known inhibitor of insulin signaling. Furthermore, a specific antisense oligodeoxynucleotide directed against SOCS-3 treatment prevented resistin from antagonizing insulin action. Conclusion: The major function of resistin on liver is to induce insulin resistance. SOCS-3 induc-tion may contribute to the resistin-mediated inhibition of insulin signaling in H4IIE hepatocytes.

  19. Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver

    International Nuclear Information System (INIS)

    Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of 125I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t/sub 1/2/) of immunoreactive insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers. Insulin binding and degradation by hepatocytes from control and cirrhotic livers showed no significant differences. Intraportal insulin infusion in perfusion studies suppressed glucagon-stimulated increases in glucose output from control livers but failed to suppress glucose production by cirrhotic livers, suggesting the presence of hepatic insulin resistance in cirrhosis. Impaired clearance of insulin and glucagon by the intact cirrhotic liver and normal binding and degradation of insulin by isolated hepatocytes suggest that factors such as intrahepatic fibrosis and shunting and postbinding defects may be responsible for the impaired hormone clearance and hepatic insulin resistance

  20. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  1. IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

    DEFF Research Database (Denmark)

    Bouzakri, K; Karlsson, HRK; Vestergaard, Henrik;

    2006-01-01

    Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied...... by altered signal transduction, skeletal muscle biopsies were obtained from pancreas-kidney transplant recipients (n = 4), nondiabetic kidney transplant recipients (receiving the same immunosuppressive drugs; n = 5), and healthy subjects (n = 6) before and during a euglycemic-hyperinsulinemic clamp. Basal...... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

  2. Relationship between blood pressure and insulin resistance in patients with gestational diabetes

    International Nuclear Information System (INIS)

    Objective: To study the relationship existe between blood pressure level and degree of insulin resistance in patients with gestational diabetes. Methods: Ninety-five cases of gestational diabetes were diagnosed among 350 pregnant women. Of them, 55 were found to be hypertensive and 40 were normotensive. Fasting, 1,2, 3h post-prandial (75g glucose) blood sugar (with peroxidase method) levels and fasting insulin (with RIA) levels were measured in these patients and 85 normal pregnant women (as control). Results: Fasting, 1, 2, 3h post 75g glucose blood sugar and fasting insulin levels in the 55 hypertensive diabetics were significantly higher than those in the normotensives and controls (P<0.05). The calculated insulin sensitivity indices were significantly lower (P also < 0.05). Conclusion: A higher insulin resistance existed in hypertensive gestational diabetics which might be a risk factor of developing hypertension. (authors)

  3. Effects of Portulaca Oleracea on Insulin Resistance in Rats with Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    沈岚; 陆付耳

    2003-01-01

    Objective: To study the effects of Portulaca oleracea, a Chinese medicinal herb, on insulin resistance in rats with type 2 diabetes mellitus (T2DM). Methods: Experimental model of T2DM was established by injection of streptozotocin (25mg/kg) and feeding with high calorie forage. The effects of Portulaca oleracea on oral glucose tolerance, serum levels of insulin, triglyceride, total cholesterol, high-density lipoproteins-cholesterol and free fatty acids, and insulin sensitivity index were all observed. Results: Portulaca oleracea could reduce the body weight, improve the impaired glucose tolerance and lipid metabolism, decrease serum free fatty acids, attenuate hyperinsulinemia and elevate insulin sensitivity. Conclusion: Portulaca oleracea could improve insulin resistance in rats with T2DM, and the mechanism might be related to its actions in improving lipid metabolism and decreasing free fatty acids.

  4. Lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling

    DEFF Research Database (Denmark)

    Høeg, Louise D; Sjøberg, Kim Anker; Jeppesen, Jacob;

    2011-01-01

    AbstractObjective: We have previously shown that overnight fasted women have higher insulin stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism...... than men. We therefore hypothesized that women would be less prone to lipid induced insulin resistance. Research and design methods: Insulin sensitivity of whole body and leg glucose disposal was studied in 16 young well matched healthy men and women infused with intralipid or saline for 7h. Muscle...... biopsies were obtained before and during a euglycemic hyperinsulinemic (1.42 mU·kg(-1)·min(-1)) clamp. Results: Intralipid infusion reduced whole body glucose infusion rate 26% in women and 38% in men (p

  5. Helicobacter pylori Infection and Insulin Resistance in Diabetic and Nondiabetic Population

    Directory of Open Access Journals (Sweden)

    Jamshid Vafaeimanesh

    2014-01-01

    Full Text Available Helicobacter pylori (HP is a common worldwide infection with known gastrointestinal and nongastrointestinal complications. One of the gastrointestinal side effects posed for this organism is its role in diabetes and increased insulin resistance. The aim of this study was to evaluate the association between HP and insulin resistance in type 2 diabetic patients and nondiabetics. This cross-sectional study was carried out from May to December 2013 on 211 diabetic patients referred to diabetes clinic of Shahid Beheshti Hospital of Qom and 218 patients without diabetes. HP was evaluated using serology method and insulin resistance was calculated using HOMA-IR. The prevalence of H. pylori infection was 55.8% and 44.2% in diabetics and nondiabetics (P=0.001. The study population was divided into two HP positive and negative groups. Among nondiabetics, insulin resistance degree was 3.01±2.12 and 2.74±2.18 in HP+ and HP− patients, respectively P=0.704. Oppositely, insulin resistance was significantly higher in diabetic HP+ patients rather than seronegative ones (4.484±2.781 versus 3.160±2.327, P=0.013. In diabetic patients, in addition to higher prevalence of HP, it causes a higher degree of insulin resistance.

  6. In Vivo Interrelationship between Insulin Resistance and Interferon Gamma Production: Protective and Therapeutic Effect of Berberine

    Science.gov (United States)

    Sahyoun, Heba Abdelghany; Elshehawy, Ashraf Abdelhamed; Elsayed, Mohammad Mohammad

    2016-01-01

    This research was conducted to investigate if there is a relation between insulin resistance incidence and inhibition of interferon gamma production or not. Firstly, insulin resistance was induced by high fat diet (HFD) intake for 6 weeks. Secondly, berberine was used as protective/curative compound for insulin resistance. Results revealed that feeding rats HFD for 6 weeks developed features of insulin resistance (IR) syndrome. These features presented in increased body weight, hyperglycemia, hyperinsulinemia, hypercholesterolemia (with increased LDL-cholesterol and decreased HDL-cholesterol), and hypertriglyceridemia. Level of antioxidant enzymes in HFD group was higher than in normal one. Also there was an increasing in level of proinflammatory cytokines as interleukin- (IL-) 6 and IL-12 in HFD group. Feeding rats HFD for 6 weeks also decreased level of interferon gamma (IFN-γ). The decreased level of IFN-γ has been shown to predict infection with infectious diseases especially viral infection. Treatment and protection with berberine 50 mg/kg/day for 2 weeks were found to be effective against the features of insulin resistance syndrome, improved levels of insulin resistance parameters, lipid profile, antioxidant enzymes, proinflammatory cytokines, and IFN-γ. PMID:27642351

  7. Does Diacylglycerol Accumulation in Fatty Liver Disease Cause Hepatic Insulin Resistance?

    Directory of Open Access Journals (Sweden)

    Brian N. Finck

    2015-01-01

    Full Text Available Numerous studies conducted on obese humans and various rodent models of obesity have identified a correlation between hepatic lipid content and the development of insulin resistance in liver and other tissues. Despite a large body of the literature on this topic, the cause and effect relationship between hepatic steatosis and insulin resistance remains controversial. If, as many believe, lipid aggregation in liver drives insulin resistance and other metabolic abnormalities, there are significant unanswered questions as to which lipid mediators are causative in this cascade. Several published papers have now correlated levels of diacylglycerol (DAG, the penultimate intermediate in triglyceride synthesis, with development of insulin resistance and have postulated that this occurs via activation of protein kinase C signaling. Although many studies have confirmed this relationship, many others have reported a disconnect between DAG content and insulin resistance. It has been postulated that differences in methods for DAG measurement, DAG compartmentalization within the cell, or fatty acid composition of the DAG may explain these discrepancies. The purpose of this review is to compare and contrast some of the relevant findings in this area and to discuss a number of unanswered questions regarding the relationship between DAG and insulin resistance.

  8. Does Diacylglycerol Accumulation in Fatty Liver Disease Cause Hepatic Insulin Resistance?

    Science.gov (United States)

    Finck, Brian N; Hall, Angela M

    2015-01-01

    Numerous studies conducted on obese humans and various rodent models of obesity have identified a correlation between hepatic lipid content and the development of insulin resistance in liver and other tissues. Despite a large body of the literature on this topic, the cause and effect relationship between hepatic steatosis and insulin resistance remains controversial. If, as many believe, lipid aggregation in liver drives insulin resistance and other metabolic abnormalities, there are significant unanswered questions as to which lipid mediators are causative in this cascade. Several published papers have now correlated levels of diacylglycerol (DAG), the penultimate intermediate in triglyceride synthesis, with development of insulin resistance and have postulated that this occurs via activation of protein kinase C signaling. Although many studies have confirmed this relationship, many others have reported a disconnect between DAG content and insulin resistance. It has been postulated that differences in methods for DAG measurement, DAG compartmentalization within the cell, or fatty acid composition of the DAG may explain these discrepancies. The purpose of this review is to compare and contrast some of the relevant findings in this area and to discuss a number of unanswered questions regarding the relationship between DAG and insulin resistance. PMID:26273583

  9. In Vivo Interrelationship between Insulin Resistance and Interferon Gamma Production: Protective and Therapeutic Effect of Berberine.

    Science.gov (United States)

    Mahmoud, Mohammad Ahmad; Ghareeb, Doaa Ahmad; Sahyoun, Heba Abdelghany; Elshehawy, Ashraf Abdelhamed; Elsayed, Mohammad Mohammad

    2016-01-01

    This research was conducted to investigate if there is a relation between insulin resistance incidence and inhibition of interferon gamma production or not. Firstly, insulin resistance was induced by high fat diet (HFD) intake for 6 weeks. Secondly, berberine was used as protective/curative compound for insulin resistance. Results revealed that feeding rats HFD for 6 weeks developed features of insulin resistance (IR) syndrome. These features presented in increased body weight, hyperglycemia, hyperinsulinemia, hypercholesterolemia (with increased LDL-cholesterol and decreased HDL-cholesterol), and hypertriglyceridemia. Level of antioxidant enzymes in HFD group was higher than in normal one. Also there was an increasing in level of proinflammatory cytokines as interleukin- (IL-) 6 and IL-12 in HFD group. Feeding rats HFD for 6 weeks also decreased level of interferon gamma (IFN-γ). The decreased level of IFN-γ has been shown to predict infection with infectious diseases especially viral infection. Treatment and protection with berberine 50 mg/kg/day for 2 weeks were found to be effective against the features of insulin resistance syndrome, improved levels of insulin resistance parameters, lipid profile, antioxidant enzymes, proinflammatory cytokines, and IFN-γ. PMID:27642351

  10. Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats

    OpenAIRE

    Nayak, Yogendra; Venkatachalam, H.; Daroji, Vijay Kumar; Mathew, Geetha; Jayashree, B. S.; Unnikrishnan, M. K.

    2014-01-01

    Synthetic 3-hydroxyflavone analogues (JY-1, JY-2, JY-3, JY-4), were tested for antidiabetic activity in high-fructose-diet-fed (66 %, for 6 weeks) insulin-resistant Wistar rats (FD-fed rats). The fasting blood glucose, insulin, creatinine and AGEs were decreased to near normal upon treatment with test compounds. Insulin resistance markers such as HOMA-IR, K-ITT, plasma triglycerides, lipids, endogenous antioxidant defense and glycogen were restored in FD-fed rats after treatment with 3-hydrox...

  11. JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity.

    Science.gov (United States)

    Solinas, Giovanni; Vilcu, Cristian; Neels, Jaap G; Bandyopadhyay, Gautam K; Luo, Jun-Li; Naugler, Willscott; Grivennikov, Sergei; Wynshaw-Boris, Anthony; Scadeng, Miriam; Olefsky, Jerrold M; Karin, Michael

    2007-11-01

    Obesity-induced insulin resistance is a major factor in the etiology of type 2 diabetes, and Jun kinases (JNKs) are key negative regulators of insulin sensitivity in the obese state. Activation of JNKs (mainly JNK1) in insulin target cells results in phosphorylation of insulin receptor substrates (IRSs) at serine and threonine residues that inhibit insulin signaling. JNK1 activation is also required for accumulation of visceral fat. Here we used reciprocal adoptive transfer experiments to determine whether JNK1 in myeloid cells, such as macrophages, also contributes to insulin resistance and central adiposity. Our results show that deletion of Jnk1 in the nonhematopoietic compartment protects mice from high-fat diet (HFD)-induced insulin resistance, in part through decreased adiposity. By contrast, Jnk1 removal from hematopoietic cells has no effect on adiposity but confers protection against HFD-induced insulin resistance by decreasing obesity-induced inflammation. PMID:17983584

  12. The insulin-resistant phenotype of polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Svendsen, Pernille Fog; Madsbad, Sten; Nilas, Lisbeth

    2009-01-01

    OBJECTIVE: To investigate the individual parameters included in the diagnosis of polycystic ovary syndrome (PCOS), and their impact on insulin sensitivity. DESIGN: Cross-sectional study. SETTING: Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Hvidovre, Denmark. PATIENT......(S): Sixty-one women; 36 women with PCOS and 25 age- and weight-matched control women were investigated. INTERVENTION(S): Peripheral insulin sensitivity was evaluated by the hyperinsulinemic euglycemic clamp, glucose tolerance by an oral glucose tolerance test (OGTT), and ovarian morphology by transvaginal...... assessment IR index. We found no significant association between ovarian morphology and insulin sensitivity or between menstrual frequency and insulin sensitivity. CONCLUSION(S): The PCOS is associated with IR. Body mass index, hyperandrogenemia, and hyperandrogenism are independent predictors of low insulin...

  13. Investigation of insulin resistance in narcoleptic patients: dependent or independent of body mass index?

    Directory of Open Access Journals (Sweden)

    Engel A

    2011-06-01

    Full Text Available Alice Engel1,2, Jana Helfrich1, Nina Manderscheid1, Petra B Musholt3, Thomas Forst3, Andreas Pfützner3, Norbert Dahmen1,21Department of Psychiatry, University of Mainz, Germany; 2Fachklinik Katzenelnbogen, Katzenelnbogen, Germany; 3IKFE, Institute for Clinical Research and Development, Mainz, GermanyBackground: Narcolepsy is a severe sleep-wake cycle disorder resulting in most cases from a lack of orexin, the energy balance-regulating hormone. Narcoleptic patients have been reported to suffer from an excess morbidity of Type 2 diabetes, even after correction for their often elevated body mass index.Methods: To explore whether narcolepsy is specifically associated with a propensity to develop insulin resistance, we measured fasting glucose, insulin, and intact proinsulin levels in 43 narcoleptic patients and 47 controls matched for body mass index and age. The proinsulin-to-insulin ratio was calculated. Insulin resistance was determined using the homeostatic model assessment method.Results: Narcoleptic patients did not show elevated insulin resistance parameters.Conclusion: In contrast with earlier reports, we found no evidence that narcolepsy specifically elevates the risk of insulin resistance (and consequently of type 2 diabetes independently of body mass index.Keywords: fasting glucose, insulin, intact proinsulin, narcolepsy, obesity

  14. Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology

    Directory of Open Access Journals (Sweden)

    Atul S. Deshmukh

    2016-02-01

    Full Text Available Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence, of altered protein expressions profiles and/or their posttranslational modifications (PTMs. Mass spectrometry (MS-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle proteomics are challenging. This review describes the technical limitations of skeletal muscle proteomics as well as emerging developments in proteomics workflow with respect to samples preparation, liquid chromatography (LC, MS and computational analysis. These technologies have not yet been fully exploited in the field of skeletal muscle proteomics. Future studies that involve state-of-the-art proteomics technology will broaden our understanding of exercise-induced adaptations as well as molecular pathogenesis of insulin resistance. This could lead to the identification of new therapeutic targets.

  15. Relationship among resistance to the insulin and obesity in Zacatecas population

    International Nuclear Information System (INIS)

    The Zacatecas State (Mexico) occupies the second national place in obesity, although the adults have a bigger incidence every time exist more minors that present this problem which can facilitate other illnesses like diabetes and hypertension. The first resistance references to the insulin were made by Himsworth in 1936, when he referred to insulin-resistant and insulin-sensitive diabetics. The resistance to the insulin, as event pathogen primary in the diabetes mellitus type 2 is derived of the obesity, what implies a subnormal biological response to the actions of the hormone in the carbohydrates, proteins and lipids metabolism. In this work was carried out a study of insulin levels for the Radioimmunoassay method in 40 patients with evident obesity and 8 patients with normal weight in order to evaluate these levels according to their age and abdominal circumference. Three correlations were made for both groups (obese and normal), the first correlation indicates the size of the waist with the insulin quantity, according to the arrangements that shows the correlation is bigger in all; what means that there is a great dependence among the size of the waist and the insulin quantity that contain. The second correlation is the age with the insulin that although is small, indicates that the age does not important for the insulin quantity that is secreted. The third and last realized correlation was of the age with the waist, and according to the results correlation also exists, but this is not significant as the first correlation. Therefore is considered existent the relationship between obesity and resistance to the insulin. (Author)

  16. INSULIN AND INSULIN RESISTANCE: NEW MOLECULE MARKERS AND TARGET MOLECULE FOR THE DIAGNOSIS AND THERAPY OF DISEASES OF THE CENTRAL NERVOUS SYSTEM

    Directory of Open Access Journals (Sweden)

    A. B. Salmina

    2013-01-01

    Full Text Available The review summarizes current data on the role of insulin in the regulation of t glucose metabolism in the central nervous system at physiologic and pathologic conditions. For many years, the brain has been considered as an insulin-independent organ which utilizes glucose without insulin activity. However, it is become clear now that insulin not only regulates glucose transport and metabolism, but also has modulatory efftects in impact on excitability, proliferation and differentiation of brain progenitor cells, synaptic plasticity and memory formation, secretion of neurotransmitters, apoptosis. We have critically reviewed literature information and our own data on the role of insulin and insulin resistance in neuron-glia metabolic coupling, regulation of NAD+ metabolism and action of NAdependent enzymes, neurogenesis, brain development in (pathophysiological conditions. The paper clarifies interrelations between alterations in glucose homeostasis, development of insulin resistance and development of neurodegeneration (Alzheimer's disease and Parkinson's disease, autism, stroke, and depression. We discuss the application of novel molecular markers of insulin resistance (adipokines, α-hydroxybutyrate, BDNF, insulin-regulated aminopeptidase, provasopressin and molecular targets for diagnostics and treatment of brain disorders associated with insulin resistance.

  17. Does cardiorespiratory fitness modify the association between birth weight and insulin resistance in adult life?

    Directory of Open Access Journals (Sweden)

    Tomoko Aoyama

    Full Text Available OBJECTIVE: Lower birth weight is associated with higher insulin resistance in later life. The aim of this study was to determine whether cardiorespiratory fitness modifies the association of birth weight with insulin resistance in adults. METHODS: The subjects were 379 Japanese individuals (137 males, 242 females aged 20-64 years born after 1943. Insulin resistance was assessed using a homeostasis model assessment of insulin resistance (HOMA-IR, which is calculated from fasting blood glucose and insulin levels. Cardiorespiratory fitness (maximal oxygen uptake, VO2max was assessed by a maximal graded exercise test on a cycle ergometer. Birth weight was reported according to the Maternal and Child Health Handbook records or the subject's or his/her mother's memory. RESULTS: The multiple linear regression analysis revealed that birth weight was inversely associated with HOMA-IR (β = -0.141, p = 0.003, even after adjustment for gender, age, current body mass index, mean blood pressure, triglycerides, HDL cholesterol, and smoking status. Further adjustments for VO2max made little difference in the relationship between birth weight and HOMA-IR (β = -0.148, p = 0.001, although VO2max (β = -0.376, p<0.001 was a stronger predictor of HOMA-IR than birth weight. CONCLUSIONS: The results showed that the association of lower birth weight with higher insulin resistance was little modified by cardiorespiratory fitness in adult life. However, cardiorespiratory fitness was found to be a stronger predictor of insulin resistance than was birth weight, suggesting that increasing cardiorespiratory fitness may have a much more important role in preventing insulin resistance than an individual's low birth weight.

  18. Resistance to the antilipolytic effect of insulin in adipocytes of African-American compared to Caucasian postmenopausal women

    OpenAIRE

    Fried, Susan K.; Tittelbach, Thomas; Blumenthal, Jacob; Sreenivasan, Urmila; Robey, Linda; Yi, Jamie; Khan, Sumbul; Hollender, Courtney; Ryan, Alice S.; Goldberg, Andrew P.

    2010-01-01

    High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant. We assessed possible depot and race difference in the antilipolytic effect of insulin in adipocytes isolated from abdominal (Abd) and gluteal (Glt) subcutaneous (sc) adipose tissue of overweight, postmenopausal AA and Caucasian (C) women. Percent body fat, fasting insulin, visceral adiposity, and adipocyte size was higher in AA women. Disinhibited lipoly...

  19. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men

    DEFF Research Database (Denmark)

    Alibegovic, A C; Sonne, M P; Højbjerre, L;

    2010-01-01

    Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches...... contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity....

  20. Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

    International Nuclear Information System (INIS)

    Objective: To investigate the relationship between serum tumor necrosis factor-α (TNF-α) levels and insulin resistance (IR) in patients with essential by pertension. Methods: Serum TNF-α and free insulin (fINS)levels were measured with RIA in 41 patients with essential hypertension and 38 controls. Insulin resistance was calculated with insulin resistance index (HOMA-IR). Results: The serum TNF-α levels were significantly higher in patients with essential hypertension than those in the controls (P<0.001). The HOMA-IR was also significantly higher in hypertension group than that in controls (P<0.001). Serum TNF-α levels was positively correlated with BMI, HOMA-IR and SBP both in hypertension group and control group (P<0.05). Conclusion: Serum TNF-α level was increased in hypertensive patients and positively correlated with obesity and IR. (authors)

  1. Influence of Acupuncture on Insulin Resistance in Simple Obesity Patients

    Institute of Scientific and Technical Information of China (English)

    程玲; 陈妙根; 杨晖; 何金森; 张春燕; 肖纯怡

    2007-01-01

    目的:探讨针刺对单纯性肥胖症患者胰岛素抵抗的调节作用与临床疗效.方法:采用"益气健脾,化痰消浊"法,取脐周八穴(天枢、滑肉门、外陵、阴交、水分)、关元、足三里等穴,配合耳穴贴压,并与同期30例健康体检者比较,观察针刺前后单纯性肥胖症患者FBG、INS、ISI、TC、TG、LDLC、HDLC变化;观察针刺前后单纯性肥胖症患者腰围、臀围、腰臀比、体重、BMI的变化,及其Ⅰ度肥胖、Ⅱ度肥胖的疗效差异.结果:治疗前单纯性肥胖症患者存在高胰岛素血症(HI),ISI显著下降(P<0.01),治疗后腰围、臀围、腰臀比、体重、BMI明显下降(P<0.05,P<0.01),同时FBG、INS、TC、TG、LDLC亦明显下降(P<0.01,P<0.05),ISI、HDLC明显上升(P<0.05).结论:针刺治疗不仅能有效改善单纯性肥胖症患者的体脂参数,同时也能调整单纯性肥胖症患者异常脂质代谢,改善胰岛素抵抗状态.%To investigate the regulatory effect of acupuncture on insulin resistance in simple obesity patients and its clinical effect. Methods: By the method "to benefit qi, strengthen the spleen, dissolve phlegm and remove turbidity", eight periumbilical acupoints, Tianshu (ST 25), Huaroumen (ST 24), Wailing (ST 26), Yinjiao (CV 7) and Shuifen (CV 9), and Guanyuan (CV 4) and Zusanli (ST 36) were used, in cooperation with ear-points-embedding method, and together with 30 healthy persons for comparison, in order to observe the changes in FBG, INS,ISI, TC, TG, LDLC and HDLC and to observe the changes in the waist circumference, hip circumference, waist-hip ratio, body weight and BMI in simple obesity patients before and after acupuncture treatments, and to observe the differences of the therapeutic effects between grade Ⅰ and grade Ⅱ obesity. Results: Hyperinsulinemia (HI) existed in the patients with simple obesity before the treatment, and ISI significantly decreased (P<0.01) in comparison with the healthy group, and waist

  2. Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women.

    Science.gov (United States)

    Liong, Stella; Lappas, Martha

    2016-04-15

    Sterile inflammation and infection are key mediators of inflammation and peripheral insulin resistance associated with gestational diabetes mellitus (GDM). Studies have shown endoplasmic reticulum (ER) stress to induce inflammation and insulin resistance associated with obesity and type 2 diabetes, however is paucity of studies investigating the effects of ER stress in skeletal muscle on inflammation and insulin resistance associated with GDM. ER stress proteins IRE1α, GRP78 and XBP-1s were upregulated in skeletal muscle of obese pregnant women, whereas IRE1α was increased in GDM women. Suppression of ER stress, using ER stress inhibitor tauroursodeoxycholic acid (TUDCA) or siRNA knockdown of IRE1α and GRP78, significantly downregulated LPS-, poly(I:C)- or IL-1β-induced production of IL-6, IL-8, IL-1β and MCP-1. Furthermore, LPS-, poly(I:C)- or TNF-α-induced insulin resistance was improved following suppression of ER stress, by increasing insulin-stimulated phosphorylation of IR-β, IRS-1, GLUT-4 expression and glucose uptake. In summary, our inducible obesity and GDM-like models suggests that the development of GDM may be involved in activating ER stress-induced inflammation and insulin resistance in human skeletal muscle. PMID:26902174

  3. Potential Roles of Stevia rebaudiana Bertoni in Abrogating Insulin Resistance and Diabetes: A Review

    Directory of Open Access Journals (Sweden)

    Nabilatul Hani Mohd-Radzman

    2013-01-01

    Full Text Available Insulin resistance is a key factor in metabolic disorders like hyperglycemia and hyperinsulinemia, which are promoted by obesity and may later lead to Type II diabetes mellitus. In recent years, researchers have identified links between insulin resistance and many noncommunicable illnesses other than diabetes. Hence, studying insulin resistance is of particular importance in unravelling the pathways employed by such diseases. In this review, mechanisms involving free fatty acids, adipocytokines such as TNFα and PPARγ and serine kinases like JNK and IKKβ, asserted to be responsible in the development of insulin resistance, will be discussed. Suggested mechanisms for actions in normal and disrupted states were also visualised in several manually constructed diagrams to capture an overall view of the insulin-signalling pathway and its related components. The underlying constituents of medicinal significance found in the Stevia rebaudiana Bertoni plant (among other plants that potentiate antihyperglycemic activities were explored in further depth. Understanding these factors and their mechanisms may be essential for comprehending the progression of insulin resistance towards the development of diabetes mellitus.

  4. Insulin resistance, small LDL particles, and risk for atherosclerotic disease.

    Science.gov (United States)

    Toth, Peter P

    2014-01-01

    There is a global epidemic of obesity, metabolic syndrome, and diabetes mellitus. Insulin resistance (IR) is etiologic for both metabolic syndrome and diabetes mellitus. IR induces a broad range of toxic systemic effects, including dyslipidemia, hypertension, hyperglycemia, increased production of advanced glycosylation end products, increased inflammatory tone, as well as a prothrombotic and pro-oxidative state. Patients with IR are highly vulnerable to the development of accelerated atherosclerosis as well its clinical sequelae, including coronary artery disease and myocardial infarction, carotid artery disease and ischemic stroke, peripheral arterial disease and claudication/lower extremity amputation, and coronary mortality. Among the most important risk factors patients afflicted with IR develop is the so-called atherogenic lipid triad: large numbers of small, dense low-density lipoprotein (sdLDL) particles, hypertriglyceridemia, and low serum concentrations of high-density lipoprotein cholesterol. Though controversial, much recent evidence suggests that the formation of sdLDL particles in the setting of IR is an important metabolic transition. Some studies suggest that these smaller particles are more atherogenic than their larger, more buoyant counterparts. At least part of the explanation for the apparent augmented atherogenicity of small LDL particles is their reduced systemic clearance by the LDL receptor, increased vulnerability to oxidation rendering them more apt for scavenging by macrophages, and possible increased flux into the subendothelial space of arterial walls. Numerous small studies suggest that sdLDL is highly correlated with cardiovascular events. Cardiovascular medicine is in need of a large prospective, randomized study that would more definitively investigate the impact of small, dense LDL (sdLDL) on risk for cardiovascular disease and whether therapeutic interventions designed to specifically reduce the burden of sdLDL are associated

  5. The relationship between rosacea and insulin resistance and metabolic syndrome.

    Science.gov (United States)

    Akin Belli, Asli; Ozbas Gok, Seyran; Akbaba, Gulhan; Etgu, Fatma; Dogan, Gursoy

    2016-06-01

    Rosacea is a chronic inflammatory skin disease affecting the face. A positive correlation has been found between rosacea and cardiovascular diseases. We sought to investigate the relation between rosacea and metabolic syndrome (MS) and insulin resistance (IR). Between January and June 2015, a case-control study including 47 age-, gender-, and body mass index (BMI)-matched rosacea patients and 50 controls was conducted. Demographic data, clinical features of rosacea patients, anthropometric measures, laboratory findings, blood pressure levels, BMI, smoking history, alcohol consumption, sports life, family history of cardiovascular disease, and presence of MS and IR were recorded. Forty-seven rosacea patients (12 men and 35 women; age range: 35-68 years) and 50 controls (11 men and 39 women; age range: 38-78 years) were included in our study. Of 47 rosacea patients, 24 had erythematotelangiectatic type, 22 had papulopustular type, and one had phymatous type. Whereas the rate of IR was significantly higher in the rosacea group, there was no significant difference in the rate of MS between rosacea and the control group (p = 0.009 and p = 0.186, respectively). In addition, the rosacea group had significantly higher fasting blood glucose, total cholesterol, and systolic and diastolic blood pressure levels (p<0.05). Mean levels of LDL, triglyceride, total cholesterol and CRP were significantly higher than in the control group (p<0.05). Our findings suggest that there is a relationship between rosacea and IR and some parameters of cardiovascular risk factors. We recommend investigation of IR in rosacea patients. PMID:27328660

  6. Role of insulin resistance and diet in acne.

    Science.gov (United States)

    Kumari, Rashmi; Thappa, Devinder Mohan

    2013-01-01

    There is increasing evidence in support of the interplay of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signaling during puberty, which have a causal role in pathogenesis of acne by influencing adrenal and gonadal androgen metabolism. Milk consumption and hyperglycemic diets can induce insulin and IGF-1-mediated PI3K ⁄ Akt-activation inducing sebaceous lipogenesis, sebocyte, and keratinocyte proliferation, which can aggravate acne. Occurence of acne as part of various syndromes also provides evidence in favor of correlation between IGF-1 and acne. PMID:23619434

  7. Role of insulin resistance and diet in acne

    Directory of Open Access Journals (Sweden)

    Rashmi Kumari

    2013-01-01

    Full Text Available There is increasing evidence in support of the interplay of growth hormone (GH, insulin, and insulin-like growth factor-1 (IGF-1 signaling during puberty, which have a causal role in pathogenesis of acne by influencing adrenal and gonadal androgen metabolism. Milk consumption and hyperglycemic diets can induce insulin and IGF-1-mediated PI3K ⁄ Akt-activation inducing sebaceous lipogenesis, sebocyte, and keratinocyte proliferation, which can aggravate acne. Occurence of acne as part of various syndromes also provides evidence in favor of correlation between IGF-1 and acne.

  8. STEAROYL-CoA DESATURASE-1 DEFICIENCY ATTENUATES OBESITY AND INSULIN RESISTANCE IN LEPTIN-RESISTANT OBESE MICE

    OpenAIRE

    Miyazaki, Makoto; Sampath, Harini; Liu, Xueqing; Flowers, Matthew T.; Chu, Kiki; Dobrzyn, Agnieszka; Ntambi, James M.

    2009-01-01

    Obesity and adiposity greatly increase the risk for secondary conditions such as insulin resistance. Mice deficient in the enzyme stearoyl-CoA desaturase-1 (SCD1) are lean and protected from diet-induced obesity and insulin resistance. In order to determine the effect of SCD1 deficiency on various mouse models of obesity, we introduced a global deletion of the Scd1 gene into leptin-deficient ob/ob mice, leptin-resistant Agouti (Ay/a) mice, and high-fat diet-fed obese (DIO) mice. SCD1 deficien...

  9. Study of Insulin Resistance and Dyslipidemia in Psoriasis Patients in a Tertiary Care Hospital, South India

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    Doddarangaiah R. Shivanand

    2016-01-01

    Full Text Available Background: Psoriasis is a chronic immune mediated inammatory skin disease with a prevalence of 1–3% in the general population. In recent years, psoriasis has been recognized as a systemic disease associated with metabolic syndrome or its components such as: obesity, insulin resistance, hypertension and atherogenic dyslipidemia. Aim & Objectives: To investigate the metabolic state in psoriatic patients in order to clarify the association of psoriasis with insulin resistance and dyslipidemia. Material and Methods: The study included 52 psoriasis patients who attended the Outpatient Department of Dermatology at Shridevi Institute of Medical Sciences and Research Hospital, Tumkur, Karnataka, India. The cases were divided into mild (n=28 and severe (n=24 category based on the Psoriasis Area and Severity Index (PASI score. Fifty healthy controls were also included in the study. Fasting blood glucose, fasting insulin, insulin resistance by Homeostasis Model Assessment (HOMA-IR method and lipid prole were measured in both cases and controls. Results: The fasting insulin levels and insulin resistance measured by HOMA-IR method were signicantly (P<0.05 higher in mild and severe psoriasis cases when compared to healthy controls. Total Cholesterol, triacyl glycerol, LDLCholesterol levels were signicantly (P<0.05 higher in mild and severe psoriasis cases in comparison with controls. HDL-Cholesterol levels were signicantly (P<0.05 lower in both mild and severe cases when compared to controls. Conclusion: Our ndings in this study showed that psoriasis is associated with components of metabolic syndrome like insulin resistance and atherogenic dyslipidemia which are considered to be predisposing factors for diabetes mellitus and cardiovascular diseases. The early detection of insulin resistance and dyslipidemia in psoriasis patients could help them reduce the risk of development of diabetes mellitus and cardiovascular diseases by modifying

  10. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C-W.; Biggar, K.K.; Storey, K.B. [Carleton University, Department of Biology, Institute of Biochemistry, Ottawa, ON (Canada)

    2013-01-28

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans.

  11. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    International Nuclear Information System (INIS)

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans

  12. Relationship between insulinase activity of erythrocytes and insulin resistance in patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    LI Chen-zhong; ZHANG Su-hua; QIU Hong-xin; WANG Ding-nian

    2001-01-01

    To investigate the relationship between insulinase activity of erythrocytes (EIA) and insulin resistance in patients with type 2 diabetes mellitus. Methods: EIA was determined with the method of radioassay of enzyme activity in 65 healthy subjects, and 109 patients with type 2 diabetes mellitus divided into 3 subgroups according to their therapy and plasma glucose control. Fasting plasma insulin (FINS) and other related indices were also measured in all the subjects. Moreover, insulin sensitive index (lSI) was calculated for estimation of insulin sensitivity. Results: EIA and FINS are increased in two subgroups of diabetic patients on hypoglycemics (subgroup A and subgroup B), and especially higher in the poor controlled subgroup of patients ( subgroup A). EIA and FINS are normal in subgroup of patients without medication (subgroup C). Moreover, ISI is decreased in all the subgroups of patients as compared with normal subjects. Correlation analysis show that EIA is inversely correlated with ISI in all subgroups of patients and normal subjects, and positively correlated with FINS in normal subjects. Conclusions:The rate of insulin degradation in erythrocytes is increased in patients with type 2 diabetes, and increased insulin degradation may result in their insulin- resistant state. Moreover, EIA may be used as one of the indices for estimation of insulin sensitivity.

  13. Impaired translocation of GLUT4 results in insulin resistance of atrophic soleus muscle.

    Science.gov (United States)

    Xu, Peng-Tao; Song, Zhen; Zhang, Wen-Cheng; Jiao, Bo; Yu, Zhi-Bin

    2015-01-01

    Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

  14. Impaired Translocation of GLUT4 Results in Insulin Resistance of Atrophic Soleus Muscle

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    Peng-Tao Xu

    2015-01-01

    Full Text Available Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

  15. Study on the Relationship between Insulin-Resistance and Syndrome Differentiation Typing in Hypertension Patients

    Institute of Scientific and Technical Information of China (English)

    刘惠文; 张铁忠; 李光伟; 姜亚云

    2001-01-01

    Objective:To find the relationship between insulin-resistance and Syndrome Differentiation type (SDT) in hypertensive patients.Methods: Two hundred and nine patients of early stage hypertention with no complications of heart, brain or kidney were selected and classified into 4 types according to SDT, the Liver-Fire exuberant type (A), the Phlegm-Dampness abundant type (B), the Yin-Deficiency and Yang-Excess type (C) and the Deficiency of both Yin and Yang type (D). Their insulin sensitivity was examined and compared with that of 40 healthy subjects.Results:(1) Compared with the healthy subjects, all hypertensive patients had apparent insulin resistance (P<0.05).If the insulin sensitivity of healthy subjects was defined as 1.00, that of patients of type A, B, C and D were 0.54, 0.58, 0.65 and 0.80 respectively. (2) The insulin sensitivity of patients in the 4 SDT groups were compared and no significant difference was found in comparison between group A, B and C, while significant difference was found when the other three groups were compared with group D (P<0.05), the insulin sensitivity of type D was close to that of the healthy subjects. (3) The fasting blood insulin of type D was obviously lower and the insulin sensitivity of type D was obviously higher than that of the other three types as a whole (P=0.0001). (4) Multivariate regression analysis demonstrated that insulin sensitivity was closely correlated with SDT (P=0.0001). Conclusion: Insulin resistance is one of the pathological basis for SDT in hypertension.

  16. mRNA expression of diacylglycerol kinase isoforms in insulin-sensitive tissues: effects of obesity and insulin resistance.

    Science.gov (United States)

    Mannerås-Holm, Louise; Kirchner, Henriette; Björnholm, Marie; Chibalin, Alexander V; Zierath, Juleen R

    2015-04-01

    Diacylglycerol kinase (DGK) isoforms regulate signal transduction and lipid metabolism. DGKδ deficiency leads to hyperglycemia, peripheral insulin resistance, and metabolic inflexibility. Thus, dysregulation of other DGK isoforms may play a role in metabolic dysfunction. We investigated DGK isoform mRNA expression in extensor digitorum longus (EDL) and soleus muscle, liver as well as subcutaneous and epididymal adipose tissue in C57BL/6J mice and obese and insulin-resistant ob/ob mice. All DGK isoforms, except for DGKκ, were detectable, although with varying mRNA expression. Liver DGK expression was generally lowest, with several isoforms undetectable. In soleus muscle, subcutaneous and epididymal adipose tissue, DGKδ was the most abundant isoform. In EDL muscle, DGKα and DGKζ were the most abundant isoforms. In liver, DGKζ was the most abundant isoform. Comparing obese insulin-resistant ob/ob mice to lean C57BL/6J mice, DGKβ, DGKι, and DGKθ were increased and DGKε expression was decreased in EDL muscle, while DGKβ, DGKη and DGKθ were decreased and DGKδ and DGKι were increased in soleus muscle. In liver, DGKδ and DGKζ expression was increased in ob/ob mice. DGKη was increased in subcutaneous fat, while DGKζ was increased and DGKβ, DGKδ, DGKη and DGKε were decreased in epididymal fat from ob/ob mice. In both adipose tissue depots, DGKα and DGKγ were decreased and DGKι was increased in ob/ob mice. In conclusion, DGK mRNA expression is altered in an isoform- and tissue-dependent manner in obese insulin-resistant ob/ob mice. DGK isoforms likely have divergent functional roles in distinct tissues, which may contribute to metabolic dysfunction. PMID:25847921

  17. The Relationship between Serum 25-Hydroxyvitamin D Concentration, Cardiorespiratory Fitness, and Insulin Resistance in Japanese Men

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    Xiaomin Sun

    2014-12-01

    Full Text Available Here, we aim to investigate the independent and combined associations of serum 25-hydroxyvitamin D (25(OHD and cardiorespiratory fitness (CRF with glucose metabolism. Fasting blood samples of 107 men aged 40–79 years were analyzed for 25(OHD, glucose, insulin, glycated hemoglobin, and lipid profile. Homeostasis model assessment of insulin resistance index (HOMA-IR was calculated from the fasting concentrations of glucose and insulin. Visceral fat area (VFA was determined by magnetic resonance imaging and CRF by measuring maximal oxygen uptake. Median 25(OHD concentration was 36.3 nmol/L, while the prevalence of 25(OHD deficiency was 74.8%. Participants with high CRF had significantly lower HOMA-IR, glycated hemoglobin, and insulin values than participants with low CRF (p < 0.05. Higher 25(OHD concentration was strongly correlated with lower HOMA-IR and insulin values independent of VFA (p < 0.01 but significantly affected by CRF. In the high CRF group, participants with higher 25(OHD concentration had lower HOMA-IR values than participants with low 25(OHD concentration (p < 0.05. Higher 25(OHD and CRF are crucial for reducing insulin resistance regardless of abdominal fat. In addition, higher 25(OHD concentration may strengthen the effect of CRF on reducing insulin resistance in middle-aged and elderly Japanese men with high CRF.

  18. Lipid-induced cell stress and insulin resistance

    OpenAIRE

    Schrauwen, Patrick

    2006-01-01

    In our Westernized society, although some excess body fat is stored inside its proper place, adipose tissue, the surplus of circulating fatty acids is also excessively stored in the liver, heart, pancreas and skeletal muscle. In these tissues, intracellular fat accumulation, in combination with a low oxidative capacity, is associated with decreased insulin sensitivity. Although the exact mechanism behind the negative effect of intracellular lipid accumulation on insulin sensitivity has not be...

  19. Recent Advances in Obesity-Induced Inflammation and Insulin Resistance

    OpenAIRE

    Tateya, Sanshiro; Kim, Francis; Tamori, Yoshikazu

    2013-01-01

    It has been demonstrated in rodents and humans that chronic inflammation characterized by macrophage infiltration occurs mainly in adipose tissue or liver during obesity, in which activation of immune cells is closely associated with insulin sensitivity. Macrophages can be classified as classically activated (M1) macrophages that support microbicidal activity or alternatively activated (M2) macrophages that support allergic and antiparasitic responses. In the context of insulin action, M2 mac...

  20. Recent Advances in Obesity-induced Inflammation and Insulin Resistance.

    OpenAIRE

    Sanshiro eTateya; Francis eKim; Yoshikazu eTamori

    2013-01-01

    It has been demonstrated in rodents and humans that chronic inflammation characterized by macrophage infiltration occurs mainly in adipose tissue or liver during obesity, in which activation of immune cells is closely associated with insulin sensitivity. Macrophages can be classified as classically activated (M1) macrophages that support microbicidal activity or alternatively activated (M2) macrophages that support allergic and antiparasitic responses. In the context of insulin action, M2 mac...

  1. Insulin resistance in H pylori infection and its association with oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Mehmet Aslan; Mehmet Horoz; Yasar Nazligul; Cengiz Bolukbas; F Fusun Bolukbas; Sahbettin Selek; Hakim Celik; Ozcan Erel

    2006-01-01

    AIM:To determine the insulin resistance (IR) and oxidative status in H pylori infection and to find out if there is any relationship between these parameters and insulin resistance.METHODS:Fifty-five H pylori positive and 48 H pylori negative patients were enrolled. The homeostasis model assessment (HOMA) was used to assess insulin resistance. Serum total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined in all subjects.RESULTS:The total antioxidant capacity was significantly lower in H pylori positive group than in H pylori negative group (1.36 ± 0.33 and 1.70 ± 0.50,respectively; P < 0.001), while the total oxidant status and oxidative stress index were significantly higher in H pylori positive group than in H pylori negative group (6.79 ± 3.40 and 5.08 ± 0.95, and 5.42 ± 3.40 and 3.10± 0.92, respectively; P < 0.001). Insulin resistance was significantly higher in H pylori positive group than in H pylori negative group (6.92 ± 3.86 and 3.61 ± 1.67, respectively; P < 0.001). Insulin resistance was found to be significantly correlated with total antioxidant capacity (r= -0.251, P < 0.05), total oxidant status (r = 0.365, P <0.05), and oxidative stress index (r = 0.267, P < 0.05).CONCLUSION: Insulin resistance seems to be associated with increased oxidative stress in H pylori infection.Further studies are needed to clarify the mechanisms underlying this association and elucidate the effect of adding antioxidant vitamins to H pylori eradication therapy on insulin resistance during H pylori infection.

  2. Insulin resistance, adiponectin and adverse outcomes following elective cardiac surgery: a prospective follow-up study

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    Hjortdal Vibeke E

    2010-12-01

    Full Text Available Abstract Background Insulin resistance and adiponectin are markers of cardio-metabolic disease and associated with adverse cardiovascular outcomes. The present study examined whether preoperative insulin resistance or adiponectin were associated with short- and long-term adverse outcomes in non-diabetic patients undergoing elective cardiac surgery. Methods In a prospective study, we assessed insulin resistance and adiponectin levels from preoperative fasting blood samples in 836 patients undergoing cardiac surgery. Population-based medical registries were used for postoperative follow-up. Outcomes included all-cause death, myocardial infarction or percutaneous coronary intervention, stroke, re-exploration, renal failure, and infections. The ability of insulin resistance and adiponectin to predict clinical adverse outcomes was examined using receiver operating characteristics. Results Neither insulin resistance nor adiponectin were statistically significantly associated with 30-day mortality, but adiponectin was associated with an increased 31-365-day mortality (adjusted odds ratio 2.9 [95% confidence interval 1.3-6.4] comparing the upper quartile with the three lower quartiles. Insulin resistance was a poor predictor of adverse outcomes. In contrast, the predictive accuracy of adiponectin (area under curve 0.75 [95% confidence interval 0.65-0.85] was similar to that of the EuroSCORE (area under curve 0.75 [95% confidence interval 0.67-0.83] and a model including adiponectin and the EuroSCORE had an area under curve of 0.78 [95% confidence interval 0.68-0.88] concerning 31-365-day mortality. Conclusions Elevated adiponectin levels, but not insulin resistance, were associated with increased mortality and appear to be a strong predictor of long-term mortality. Additional studies are warranted to further clarify the possible clinical role of adiponectin assessment in cardiac surgery. Trial Registration The Danish Data Protection Agency; reference no

  3. Adiposity, Biological Markers of Disease, and Insulin Resistance in Mexican American Adolescents, 2004-2005

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    Anne R. Rentfro, PhD, RN

    2011-03-01

    Full Text Available IntroductionRates of obesity and overweight, which frequently lead to type 2 diabetes, have increased dramatically among US children during the past 30 years. We analyzed associations between insulin resistance and other markers of disease in a sample of Mexican American adolescents from a severely disadvantaged community on the Texas-Mexico border.MethodsWe analyzed results from 325 students from 1 high school in this descriptive study. We measured height, weight, waist circumference, blood pressure, blood glucose, and lipids; calculated body mass index; and estimated insulin resistance.ResultsApproximately 50% of our sample (mean age, 16 y were overweight or obese, and more participants were obese than overweight. More than 40% had high waist circumference, and 66% had elevated high-density lipoprotein cholesterol. These characteristics were already present in the youngest participants (aged 12 y. Although only 1% of participants had elevated fasting blood glucose, 27% exhibited insulin resistance and most of these were also obese. Similarly, participants with high waist circumference were more likely to exhibit insulin resistance than those with normal waist circumference.ConclusionParticipants in this sample had insulin resistance, a potent predictor of diabetes. Two markers, low high-density lipoprotein cholesterol and high waist circumference, were strongly linked to insulin resistance; the surrogate for central adiposity, waist circumference, exhibited strong association. We identified high levels of obesity and markers for future disease in our sample. These findings emphasize the need to address insulin resistance at least as early as adolescence to prevent adverse economic, social, and health consequences.

  4. Effects of high-sucrose feeding on insulin resistance and hemodynamic responses to insulin in spontaneously hypertensive rats.

    Science.gov (United States)

    Mélançon, Sébastien; Bachelard, Hélène; Badeau, Mylène; Bourgoin, Frédéric; Pitre, Maryse; Larivière, Richard; Nadeau, André

    2006-06-01

    This study was designed to investigate the effects of a sucrose diet on vascular and metabolic actions of insulin in spontaneously hypertensive rats (SHR). Male SHR were randomized to receive a sucrose or regular chow diet for 4 wk. Age-matched, chow-fed Wistar-Kyoto (WKY) rats were used as normotensive control. In a first series of experiments, the three groups of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and blood flows. Insulin sensitivity was assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine glucose transport activity in isolated muscles and to determine endothelial nitric oxide synthase (eNOS) protein expression in muscles and endothelin content in vascular tissues. Sucrose feeding was shown to markedly enhance the pressor response to insulin and its hindquarter vasoconstrictor effect when compared with chow-fed SHR. A reduction in eNOS protein content in muscle, but no change in vascular endothelin-1 protein, was noted in sucrose-fed SHR when compared with WKY rats, but these changes were not different from those noted in chow-fed SHR. Similar reductions in insulin-stimulated glucose transport were observed in soleus muscles from both groups of SHR when compared with WKY rats. In extensor digitorum longus muscles, a significant reduction in insulin-stimulated glucose transport was only seen in sucrose-fed rats when compared with the other two groups. Environmental factors, that is, high intake of simple sugars, could possibly potentiate the genetic predisposition in SHR to endothelial dysfunction and insulin resistance.

  5. Correlation between maternal weight and insulin resistance in second half of pregnancy

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    Lucius Chidiebere Imoh

    2014-01-01

    Full Text Available Background: In pregnancy, routine measurement of maternal weight gives a crude assessment of maternal and foetal well-being. Excess weight gain in pregnancy is related to increased risk for gestational diabetes mellitus (GDM, hypertension in pregnancy and foetal macrosomia. In the Nigerian context, lack of knowledge of pre-pregnancy weight coupled with late booking of women in pregnancy hinders accurate assessment of weight gain in pregnancy. The absolute maternal weight is often used as surrogate. This study evaluates the relationship between absolute weight in the second half of pregnancy and insulin resistance. Patients and Methods: The weight of hundred pregnant women was measured between 24 to 32 weeks of pregnancy and their insulin resistance was measured using Homeostatic Model Assessment (HOMA-IR from fasting serum glucose and fasting serum insulin. Results: Twenty-six women had weight ≥95 kg and 74 women had weight of <95 kg. There was a significant positive correlation between weight and HOMA-IR (r = 0.248, fasting glucose (r = 0.198, and fasting insulin (r = 0.228, (P < 0.05. The mean weight, HOMA-IR, fasting glucose and fasting insulin were higher in women with weight ≥95 kg compared to those with less weight. Also maternal weight ≥ 95 kg was associated with severe insulin resistance, (Odds Ratio = 3.1. Conclusion: Absolute weight in pregnancy correlates well with insulin resistance. Women having weight ≥95 kg between 24-32 weeks of gestation were more likely to have severe insulin resistance with implications for increased risk of GDM and other complications.

  6. Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Mi-Young Kim

    2012-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by fat accumulation in the liver not due to alcohol abuse. NAFLD is accompanied by variety of symptoms related to metabolic syndrome. Although the metabolic link between NAFLD and insulin resistance is not fully understood, it is clear that NAFLD is one of the main cause of insulin resistance. NAFLD is shown to affect the functions of other organs, including pancreas, adipose tissue, muscle and inflammatory systems. Currently efforts are being made to understand molecular mechanism of interrelationship between NAFLD and insulin resistance at the transcriptional level with specific focus on post-translational modification (PTM of transcription factors. PTM of transcription factors plays a key role in controlling numerous biological events, including cellular energy metabolism, cell-cycle progression, and organ development. Cell type- and tissue-specific reversible modifications include lysine acetylation, methylation, ubiquitination, and SUMOylation. Moreover, phosphorylation and O-GlcNAcylation on serine and threonine residues have been shown to affect protein stability, subcellular distribution, DNA-binding affinity, and transcriptional activity. PTMs of transcription factors involved in insulin-sensitive tissues confer specific adaptive mechanisms in response to internal or external stimuli. Our understanding of the interplay between these modifications and their effects on transcriptional regulation is growing. Here, we summarize the diverse roles of PTMs in insulin-sensitive tissues and their involvement in the pathogenesis of insulin resistance.

  7. A Study on the Factors influencing insulin resistance in obese adolescents

    Institute of Scientific and Technical Information of China (English)

    Yongmei Jin; Pengfei Dou

    2008-01-01

    Objective: To explore the factors influencing insulin resistance in obese Chinese children. Methods: We randomly selected 53 children with uncomplicated obesity between 9 to14 years of age, and 29 normal healthy children, matched for age and sex. Anthropometric and plasma biochemical variables(including lipid profiles, glucose and insulin) were measured using standard methods. We calculated insulin resistance(IR) index using homeostasis model assessment(HOMA) methods and measured plasma high-sensitivity C-reactive protein(hs-CRP) levels using nephelometric methods. All statistical analyses were conducted using the statistical package SPSS. Results: Levels of fasting serum insulin, hs-CRP, total cholesterol(TC), low density lipoproteins cholesteroi(LDL-C) and IR index were higher in obese children than in controls, while high-density lipoprotein cholesterol(HDL-C) values were lower in the obese children. There was no significant difference in levels of fasting blood glucose between the two groups. HOMA-IR was used as the dependent variable in multivariate regression analysis. Significant independent predictors for insulin resistance adjusted for waist/hip ratio, diastolic pressure (DBP), BMI, triglycerides and HDL-C level were waist circumference(WC), weight and systolic pressure(SBP). Conclusion: Waist circumference, weight and SBP are predictors of insulin resistance syndrome in Chinese adolescents

  8. Effects of smoking cessation, acute re-exposure and nicotine replacement in smokers on AIR® inhaled insulin pharmacokinetics and glucodynamics

    Science.gov (United States)

    Pan, Alan X; de la Peña, Amparo; Yeo, Kwee P; Chan, Clark; Loh, Mei T; Wise, Stephen D; Silverman, Bernard L; Muchmore, Douglas B

    2008-01-01

    Aims To explore the effects of smoking cessation and acute smoking re-exposure on the pharmacokinetic (PK) and glucodynamic (GD) profiles of AIR® inhaled insulin (AIR Insulin) with or without nicotine replacement therapy (NRT). Methods Nondiabetic smokers (n = 24) with normal pulmonary function completed a two-phase (four-period), open-label, randomized euglycaemic clamp study. During the initial study phase, subjects underwent glucose clamps following AIR Insulin dosing, shortly after smoking, 8–12 h after smoking, or following subcutaneous insulin lispro shortly after smoking. AIR Insulin PK and GD were again assessed during and after a 4-week smoking-cessation period with or without NRT. In the last study period, subjects smoked one cigarette shortly before final AIR Insulin dosing and glucose clamp, to study the effect of acute smoking re-exposure on inhaled insulin PK and GD. Results Compared with the preceding active smoking phase, the administration of AIR Insulin in nondiabetic subjects undergoing a 4-week period of smoking abstinence resulted in a decrease in PK and GD of approximately 25% (P = 0.008 for both), an effect which was greater in subjects using NRT. Following rechallenge with a single cigarette (without NRT), GD response to AIR Insulin increased significantly (P = 0.006) towards precessation levels, relative to smoking abstinence. In subjects using NRT, however, the increase in GD was less pronounced. Conclusion Smoking, smoking cessation and acute re-exposure with a single cigarette are associated with clinically significant alterations in AIR Insulin pharmacokinetics and glucodynamics. AIR Insulin should not be used by smokers or those at risk for recidivism. What is already known about this subject Only one other study (Becker et al.) has reported on the influence of smoking cessation and smoking resumption on inhaled insulin pharmacokinetics and glucodynamics, concluding that the rapid changes associated with smoking resumption carry the

  9. Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide following acute necrotizing experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Péter Hegyi; Zoltán Rakonczay Jr; Réka Sári; László Czakó; Norbert Farkas; Csaba Góg; József Németh; János Lonovics; Tamás Takács

    2004-01-01

    AIM: In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8), the process of regeneration following L-arginine (Arg)-induced pancreatitis is accelerated. In rats that were also diabetic (induced by streptozotocin, STZ), pancreatic regeneration was not observed. The aim of this study was to deduce whether the administration of exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in diabetic-pancreatitic rats.METHODS: Male Wistar rats were used for the experiments.Diabetes mellitus was induced by administering 60 mg/kg body mass of STZ intraperitoneally (i.p.), then, on d 8,pancreatitis was induced by 200 mg/100 g body mass Arg i.p. twice at an interval of 1 h. The animals were injected subcutaneously twice daily (at 7 a.m. and 7 p.m.) with 1 μg/kg of CCK-8 and/or 2 IU mixed insulin (300 g/L shortaction and 700 g/L intermediate-action insulin) for 14 d after pancreatitis induction. Following this the animals were killed and the serum amylase, glucose and insulin levels as well as the plasma glucagon levels, the pancreatic mass/body mass ratio (pm/bm), the pancreatic contents of DNA, protein, amylase, lipase and trypsinogen were measured. Pancreatic tissue samples were examined by light microscopy on paraffin-embedded sections.RESULTS: In the diabetic-pancreatitic rats treatment with insulin and CCK-8 significantly elevated pw/bm and the pancreatic contents of protein, amylase and lipase vs the rats receiving only CCK-8 treatment. CCK-8 administered in combination with insulin also elevated the number of acinar cells with mitotic activities, whereas CCK-8 alone had no effect on laboratory parameters or the mitotic activities in diabetic-pancreatitic rats.CONCLUSION: Despite the hypertrophic effect of CCK-8 being absent following acute pancreatitis in diabetic-rats,the simultaneous administration of exogenous insulin restored this effect. Our results clearly demonstrate that insulin is

  10. Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH).

    Science.gov (United States)

    Agarwal, Naresh; Sharma, Barjesh Chander

    2005-10-01

    Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin

  11. In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R;

    2005-01-01

    , human immunodeficiency virus (HIV)-infected patients with and without lipodystrophy. We studied 18 HIV-infected patients with lipodystrophy (LIPO) on antiretroviral therapy and 25 HIV-infected patients without lipodystrophy (controls) of whom 18 were on antiretroviral therapy and 7 were not. Posthepatic...... > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy....

  12. Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance

    OpenAIRE

    Svensson, H.; Wetterling, L; Bosaeus, M; Odén, B; Odén, A; Jennische, E; Edén, S; Holmäng, A; Lönn, M

    2015-01-01

    Background/Objectives: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Subjects/Methods: Twenty-two NW and 11 obese women w...

  13. The Effects of Insulin Resistance on Individual Tissues: An Application of a Mathematical Model of Metabolism in Humans.

    Science.gov (United States)

    Pearson, Taliesin; Wattis, Jonathan A D; King, John R; MacDonald, Ian A; Mazzatti, Dawn J

    2016-06-01

    Whilst the human body expends energy constantly, the human diet consists of a mix of carbohydrates and fats delivered in a discontinuous manner. To deal with this sporadic supply of energy, there are transport, storage and utilisation mechanisms, for both carbohydrates and fats, around all tissues of the body. Insulin-resistant states such as type 2 diabetes and obesity are characterised by reduced efficiency of these mechanisms. Exactly how these insulin-resistant states develop, for example whether there is an order in which tissues become insulin resistant, is an active area of research with the hope of gaining a better overall understanding of insulin resistance. In this paper, we use a previously derived system of 12 first-order coupled differential equations that describe the transport between, and storage in, different tissues of the human body. We briefly revisit the derivation of the model before parametrising the model to account for insulin resistance. We then solve the model numerically, separately simulating each individual tissue as insulin resistant, and discuss and compare these results, drawing three main conclusions. The implications of these results are in accordance with biological intuition. First, insulin resistance in a tissue creates a knock-on effect on the other tissues in the body, whereby they attempt to compensate for the reduced efficiency of the insulin-resistant tissue. Second, insulin resistance causes a fatty liver, and the insulin resistance of tissues other than the liver can cause fat to accumulate in the liver. Finally, although insulin resistance in individual tissues can cause slightly reduced skeletal muscle metabolic flexibility, it is when the whole body is insulin resistant that the biggest effect on skeletal muscle flexibility is seen. PMID:27306890

  14. Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation

    OpenAIRE

    Kalaivani Batumalaie; Muhammad Arif Amin; Dharmani Devi Murugan; Munavvar Zubaid Abdul Sattar; Nor Azizan Abdullah

    2016-01-01

    Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein e...

  15. Homeostatic model assessment of insulin resistance as a predictor of metabolic syndrome: Consequences of obesity in children and adolescents

    OpenAIRE

    Naglaa Fathy Barseem; Mohamed Ahmed Helwa

    2015-01-01

    Background: Obesity and/or insulin resistance have gained increasing attention as the core manifestations of metabolic syndrome. Objective: To evaluate insulin resistance according to homeostasis model assessment of insulin resistance index HOMA-IR in obese children and adolescents with or without metabolic syndrome at risk of type 2 diabetes mellitus. Design and subjects: 60 obese children and adolescents were recruited, metabolic syndrome was diagnosed according to the modified WHO cr...

  16. Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor

    OpenAIRE

    Zhang, Chongben; Cooper, Daniel E.; Grevengoed, Trisha J.; Li, Lei O.; Klett, Eric L.; Eaton, James M.; Harris, Thurl E.; Coleman, Rosalind A.

    2014-01-01

    Glycerol-3-phosphate acyltransferase (GPAT) activity is highly induced in obese individuals with insulin resistance, suggesting a correlation between GPAT function, triacylglycerol accumulation, and insulin resistance. We asked whether microsomal GPAT4, an isoform regulated by insulin, might contribute to the development of hepatic insulin resistance. Compared with control mice fed a high fat diet, Gpat4−/− mice were more glucose tolerant and were protected from insulin resistance. Overexpres...

  17. Determination of Insulin Resistance and Beta Cell Function in Healthy Obese and Non-obese Individuals

    International Nuclear Information System (INIS)

    Objective: To determine insulin resistance and beta cell function in healthy obese and nonobese individuals of the local population. Study Design: Case control study. Place and Duration of Study: AFIP Rawalpindi in collaboration with department of medicine military hospital(MH) Rawalpindi, from Aug 2008 to Mar 2009. Methods: Eighty obese(n=40) and non-obese(n=40) subjects were selected by non-probability convenience sampling. Plasma insulin, glucose, and serum total cholestrol were estimated in fasting state. Insulin resistance was calculated by HOMA-IR and beta cell function by HOMA- equation. Results: Significant differences were observed between obese and non-obese individuals regarding insulin resistance, beta cell function, and BMI and serum total cholesterol. Mean insulin resistance in obese group was found to be 11.1 +- 5.1(range 7.0-16.2) and in non-obese group it was 0.9+-0.4 (range 0.5-1.3). This difference was highly significant (p=0.001). There was a highly significant difference between the two groups in term of beta cell function with mean rank 60.1 for obese group and 20.9 non obese groups (Asym sig. 2 tailed 0.000). Also the correlation (r = 0.064) between insulin resistance and beta cell function in obese group is highly significant (p = 0.000). Mean serum leptin levels were lower (6.3 ng/ml) in non-obese, and high (57.2 ng/ml) in the obese group. Conclusions: Insulin resistance is found higher in obese individuals. Beta cell function is significantly different between obese and non-obese groups. (author)

  18. Baseline correlates of insulin resistance in inner city high-BMI African-American children.

    Science.gov (United States)

    Raman, Aarthi; Fitch, Mark D; Hudes, Mark L; Lustig, Robert H; Murray, Carolyn B; Ikeda, Joanne P; Fleming, Sharon E

    2008-09-01

    To characterize the influence of diet-, physical activity-, and self-esteem-related factors on insulin resistance in 8- 10-year-old African-American (AA) children with BMI greater than the 85th percentile who were screened to participate in a community-based type 2 diabetes mellitus (T2DM) prevention trial. In 165 subjects, fasting glucose- and insulin-derived values for homeostasis model assessment of insulin resistance (HOMA-IR) assessed insulin resistance. Body fatness was calculated following bioelectrical impedance analysis, and fitness was measured using laps from a 20-m shuttle run. Child questionnaires assessed physical activity, dietary habits, and self-esteem. Pubertal staging was assessed using serum levels of sex hormones. Parent questionnaires assessed family demographics, family health, and family food and physical activity habits. Girls had significantly higher percent body fat but similar anthropometric measures compared with boys, whereas boys spent more time in high-intensity activities than girls. Scores for self-perceived behavior were higher for girls than for boys; and girls desired a more slender body. Girls had significantly higher insulin resistance (HOMA-IR), compared with boys (P < 0.01). Adjusting for age, sex, pubertal stage, socioeconomic index (SE index), and family history of diabetes, multivariate regression analysis showed that children with higher waist circumference (WC) (P < 0.001) and lower Harter's scholastic competence (SC) scale (P = 0.044) had higher insulin resistance. WC and selected self-esteem parameters predicted insulin resistance in high-BMI AA children. The risk of T2DM may be reduced in these children by targeting these factors.

  19. Does insulin resistance drive the association between hyperglycemia and cardiovascular risk?

    Directory of Open Access Journals (Sweden)

    Kristine Færch

    Full Text Available Several studies have shown associations between hyperglycemia and risk of cardiovascular disease (CVD and mortality, yet glucose-lowering treatment does little to mitigate this risk. We examined whether associations between hyperglycemia and CVD risk were explained by underlying insulin resistance.In 60 middle-aged individuals without diabetes we studied the associations of fasting plasma glucose, 2-hour post oral glucose tolerance test plasma glucose, insulin sensitivity as well as body fat percentage with CVD risk. Insulin sensitivity was measured as the glucose infusion rate during a euglycemic hyperinsulinemic clamp, body fat percentage was measured by dual X-ray absorptiometry, and CVD risk was estimated using the Framingham risk score. Associations of fasting plasma glucose, 2-hour plasma glucose, insulin sensitivity and body fat percentage with the Framingham risk score were assessed in linear regression models.Both fasting and 2-hour plasma glucose levels were associated with higher Framingham risk score (fasting glucose: r(2 = 0.21; 2-hour glucose: r(2 = 0.24; P<0.001 for both, and insulin sensitivity with lower Framingham risk score (r(2 = 0.36; P<0.001. However, adjustment for insulin sensitivity and 2-hour glucose made the effect of fasting glucose non-significant (P = 0.060. Likewise, when adjusting for insulin sensitivity and fasting glucose, the association between 2-hour glucose and Framingham risk score disappeared (P = 0.143. In contrast, insulin sensitivity was still associated with Framingham risk score after adjusting for glucose levels (P<0.001. Body fat was not associated with Framingham risk score when taking insulin sensitivity into account (P = 0.550.The association between plasma glucose levels and CVD risk is mainly explained by insulin resistance, which raises the question of whether glucose lowering per se without changes in the processes that underlie hyperglycemia should be the sole clinical paradigm in the

  20. Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument; Liew, Chong Wee; Shadrach, Jennifer L.; Hu, Jiang; Katsuta, Hitoshi; Hollister-Lock, Jennifer; Qian, Weijun; Wagers, Amy J.; Kulkarni, Rohit N.

    2013-02-21

    Integrative organ cross-talk regulates key aspects of energy homeostasis and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that cross-talk between the liver and pancreatic islets modulates β-cell growth in response to insulin resistance, we used the Liver-specific Insulin Receptor Knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, and in vitro islet culture approaches, we demonstrate that humoral, non-neural, non-cell autonomous factor(s) induce β-cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β-cell proliferation in ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β-cell growth factors in insulin resistant states.

  1. Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance

    DEFF Research Database (Denmark)

    Madsen, Lise; Guerre-Millo, Michéle; Flindt, Esben N;

    2002-01-01

    Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis. Here we evaluate the ability of TTA to prevent diet-induced and genetically determined adiposity and insulin resistance. In Wistar rats fed a high fat diet, TTA administration...... completely prevented diet-induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa) rats TTA treatment reduced the epididymal adipose tissue mass and improved insulin sensitivity. All three rodent peroxisome proliferator-activated receptor (PPAR) subtypes were activated by TTA...... that a TTA-induced increase in hepatic fatty acid oxidation and ketogenesis drains fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects of TTA on fat mass accumulation and peripheral insulin sensitivity....

  2. Acute ablation of PERK results in ER dysfunctions followed by reduced insulin secretion and cell proliferation

    Directory of Open Access Journals (Sweden)

    McGrath Barbara C

    2009-09-01

    Full Text Available Abstract Background A deficiency in Perk (EIF2AK3 causes multiple neonatal defects in humans known as the Wolcott Rallison syndrome. Perk KO mice exhibit the same array of defects including permanent neonatal diabetes (PND. PND in mice was previously shown by us to be due to a decrease in beta cell proliferation and insulin secretion. The aim of this study was to determine if acute ablation of PERK in the 832/13 beta cells recapitulates these defects and to identify the primary molecular basis for beta cell dysfunction. Results The INS1 832/13 transformed rat beta cell line was transduced with a dominant-negative Perk transgene via an adenoviral vector. AdDNPerk-832/13 beta cells exhibited reduced expression of insulin and MafA mRNAs, reduced insulin secretion, and reduced cell proliferation. Although proinsulin content was reduced in AdDNPerk-832/13 beta cells, proinsulin was abnormally retained in the endoplasmic reticulum. A temporal study of the acute ablation of Perk revealed that the earliest defect seen was induced expression of two ER chaperone proteins, GRP78/BiP and ERp72. The oxidized states of ERp72 and ERp57 were also increased suggesting an imbalance in the redox state of the ER. Conclusion Acute ablation of Perk in INS 832/13 beta cells exhibited all of the major defects seen in Perk KO mice and revealed abnormal expression and redox state of key ER chaperone proteins. Dysregulation of ER chaperone/folding enzymes ERp72 and GRP78/BiP occurred early after ablation of PERK function suggesting that changes in ER secretory functions may give rise to the other defects including reduced insulin gene expression, secretion, and cell proliferation.

  3. The Effect of Different Doses of Vitamin D Supplementation on Insulin Resistance in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Rastegar Hoseini

    2016-04-01

    Full Text Available Background and Aim: Type 2 diabetes mellitus (T2DM and vitamin D deficiency are both too common during menopause. Since the effect of different doses of vitamin D supplements on blood sugar, insulin concentration  and insulin resistance are unknown, the present study aimed at investigating the effects of different doses of the vitamin D supplements on visceral fat, blood sugar, insulin concentration,  and insulin resistance in ovariectomized rats. Materials and Methods: In this randomized experimental study, 32 female Wistar rats were divided into 4 equal groups  as follows: three groups . that received vitamin D supplements (high, moderate, and low dose and one control group. After 8 weeks of different doses of vitamin D supplementation plasma concentration of glucose, insulin and HOMA-IR were measured  in the three groups. The obtained data  was statistically analyzed by means of dependent t-test and ANOVA . at the significance level of P<0.05. Results: After a period of eight-week  intervention, body weight, BMI, waist circumference, visceral fat, insulin, blood glucose and HOMA-IR at high, moderate, and low doses of vitamin D supplementation were significantly lower than those in the control group (P<0.05. High dose of vitamin D compared with moderate and low doses significantly caused reduction in insulin, blood glucose, and HOMA-IR (P<0.001 for all three variables. Conclusion: The findings of the current study showed that a high dose of vitamin D causes significant improvements in FPG, insulin, and insulin resistance  evaluated by HOMA-IR. It was also found that adding vitamin D supplements can improve glucose control in menopause model of rats.

  4. Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity

    OpenAIRE

    Yarasheski, Kevin E.; Cade, W. Todd; Overton, E Turner; Mondy, Kristin E.; HUBERT, Sara; Laciny, Erin; Bopp, Coco; Lassa-Claxton, Sherry; Reeds, Dominic N.

    2010-01-01

    The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resi...

  5. Intestine-targeted DGAT1 inhibition improves obesity and insulin resistance without skin aberrations in mice.

    Directory of Open Access Journals (Sweden)

    Naoto Tsuda

    Full Text Available OBJECTIVE: Diacylglycerol O-acyltransferase 1 (DGAT1 catalyzes the final committed step in triglyceride biosynthesis. DGAT1 null mice are known to be resistant to diet-induced obesity, and more insulin sensitive relative to the wild-type; however, the mice exhibit abnormalities in the skin. This work determined whether the intestine-targeted DGAT1 inhibitor could improve obesity and insulin resistance without skin aberrations in mice. DESIGN AND METHODS: We synthesized 2 DGAT1 inhibitors: Compound A, described in the patent application from the Japan Tobacco, and Compound B (A-922500, reported by Abbott Laboratories. Both compounds were evaluated for inhibitory activities against DGAT1 enzymes and effects on the skin in mice in vivo. Compound B was further investigated for effects on obesity and insulin resistance in diet-induced-obese (DIO mice. RESULTS: The 2 compounds comparably inhibited the DGAT1 enzyme activity and the cellular triglyceride synthesis in vitro, while they showed different distribution patterns in mice in vivo. Compound A, which distributed systemically, caused skin aberrations, while Compound B, which preferentially distributed to the intestine, improved obesity and insulin resistance without skin aberrations in DIO mice. CONCLUSIONS: Our results suggest that the intestine is the key tissue in which DGAT1 plays a role in promoting obesity and insulin resistance.

  6. A better parameter in predicting insulin resistance: Obesity plus elevated alanine aminotransferase

    Institute of Scientific and Technical Information of China (English)

    Ping-Hao Chen; Jong-Dar Chen; Yu-Cheng Lin

    2009-01-01

    AIM: To investigate the association of obesity and elevated alanine aminotransferase with insulin resistance and compare these factors with metabolic syndrome.METHODS: We enrolled a total of 1308 male workers aged from 22 to 63 years. Data was extracted from the workers’ periodic health check-ups in hospitals. All cases were from the community of northern Taiwan.This was a cross-sectional observational study from July to September in 2004. We grouped all cases into four groups, based on the quartile of homeostasis model assessment. The top fourth quartile group was defined as the group with insulin resistance. We performed multivariate logistic regression analysis for the odds ratio of the risk factors for insulin resistance.RESULTS: Compared with metabolic syndrome, the coexistence of both factors had a 4.3-fold (95% CI: 2.7-6.8) increased risk, which was more than metabolic syndrome with a 3.6-fold (95% CI: 2.6-5.0) increased risk. The two factors had a synergistic effect. The synergistic index of obesity and elevated alanine aminotransferase (ALT) was 2.1 (95% CI: 1.01-4.3).CONCLUSION: Obesity and elevated ALT are associatedwith insulin resistance. The effects are synergistic.Coexistence of them is better than metabolic syndrome in predicting insulin resistance.

  7. The passive coping Roman Low Avoidance rat, a non-obese rat model for insulin resistance

    OpenAIRE

    Boersma, G.J.; Scheurink, A. J. W.; Wielinga, P Y; Steimer, T. J.; Benthem, L.

    2009-01-01

    The aim of the study was develop to an animal model that links coping style to insulin resistance. We hypothesized that the psychogenetically selected Roman Low Avoidance (RLA) rats may serve as such a model. To test this hypothesis, we submitted both RLA and Roman High avoidance (RHA) rats to a series of intravenous glucose tolerance tests (IVGTT). These IVGTT were followed by post mortem metabolic characterization of the selection lines. It was found that plasma insulin levels are markedly ...

  8. The Relationship between Serum Ferritin and Insulin Resistance in Different Glucose Metabolism in Nonobese Han Adults

    OpenAIRE

    Bo-wei Liu; Xu-min Xuan; Jun-ru Liu; Fang-ning Li; Fu-Zai Yin

    2015-01-01

    The exact mechanism through which elevated serum ferritin promotes the development of type 2 diabetes is unknown. This study showed that ferritin concentration in impaired glucose regulation and newly diagnosed diabetes mellitus subjects of nonobesity already significantly increased when compared with normal glucose tolerant subjects of nonobesity. Elevated serum ferritin levels are associated with insulin resistance and may be not associated with the decline of insulin beta cells in differen...

  9. Insulin resistance and its relation to inflammatory status and serum lipids among young women with PCOS

    OpenAIRE

    Asmathulla S; Rupa Vani K; Kripa S; Rajarajeswari R.

    2013-01-01

    Background: The incidence of polycystic ovarian syndrome (PCOS) is increasing among young women. PCOS women have decreased insulin sensitivity independent of body mass index with increase in lipid levels. Studies on measuring inflammatory status in PCOS showed varying results. The inter-relationship between inflammatory status, insulin resistance and lipid levels among PCOS women was studied. Methods: Twenty PCOS women and 20 healthy controls of age 18-25 years were recruited. Fasting blood s...

  10. Quercetin improves insulin resistance and hepatic lipid accumulation in vitro in a NAFLD cell model

    OpenAIRE

    Li, Xiuli; Wang, Rong; Zhou, Na; Wang, Xiaohui; Liu, Qingyan; BAI, YUQIN; Bai, Yin; Liu, Zhijie; Yang, Huiming; ZOU, JIHONG; Wang, Hongxia; SHI, TIEWEI

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases in the absence of significant alcohol consumption. The aim of this study was to investigate the effect of quercetin on insulin resistance and lipid metabolic abnormalities in free fatty acid (FFA)- and insulin-induced HepG2 cell model of NAFLD, and to determine the possible underlying mechanism. Quercetin markedly improves hepatic lipid accumulation and decreases the levels of triglyceride (TG). The lipid-lower...

  11. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome

    OpenAIRE

    Kadowaki, Takashi; Yamauchi, Toshimasa; KUBOTA, Naoto; Hara, Kazuo; Ueki, Kohjiro; Tobe, Kazuyuki

    2006-01-01

    Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic ...

  12. Association of adiponectin gene polymorphism with adiponectin levels and risk for insulin resistance syndrome

    OpenAIRE

    Jai Prakash; Balraj Mittal; Shally Awasthi; Neena Srivastava

    2015-01-01

    Background: Adiponectin is an abundant adipose tissue-derived protein with anti-atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease and low adiponectin levels also predict insulin resistance (IR). Methods: Case-control study in which 642 male and female subjects were participated from the North Indian population. Lipid, insulin, leptin and adiponectin level were estimated using standar...

  13. Impaired Mitochondrial Function and Insulin Resistance of Skeletal Muscle in Mitochondrial Diabetes

    OpenAIRE

    Szendroedi, Julia; Schmid, Albrecht Ingo; Meyerspeer, Martin; Cervin, Camilla; Kacerovsky, Michaela; Smekal, Gerhard; Gräser-Lang, Sabine; Groop, Leif; Roden, Michael

    2009-01-01

    OBJECTIVE Impaired muscular mitochondrial function is related to common insulin resistance in type 2 diabetes. Mitochondrial diseases frequently lead to diabetes, which is mostly attributed to defective β-cell mitochondria and secretion. RESEARCH DESIGN AND METHODS We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using 31P/1H magnetic resonance spectroscopy and insulin sensitivity and endogeno...

  14. Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism.

    Directory of Open Access Journals (Sweden)

    Yazmin Macotela

    Full Text Available Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor--leucine--can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism. Mice were placed on a normal or high fat diet (HFD. Dietary leucine was doubled by addition to the drinking water. mRNA, protein and complete metabolomic profiles were assessed in the major insulin sensitive tissues and serum, and correlated with changes in glucose homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance.

  15. Diet, insulin resistance, and obesity: zoning in on data for Atkins dieters living in South Beach.

    Science.gov (United States)

    Lara-Castro, Cristina; Garvey, W Timothy

    2004-09-01

    Insulin resistance is a central pathogenic factor for the metabolic syndrome and is associated with both generalized obesity and the accumulation of fat in the omental and intramyocellular compartments. In the context of the current obesity epidemic, it is imperative to consider diets in terms of their ability to both promote weight loss and ameliorate insulin resistance. Weight loss under any dietary formulation depends on hypocaloric intake, and only moderate weight loss (5-10%) is sufficient to augment insulin sensitivity. However, increments in insulin sensitivity may be more directly related to loss of intramyocellular or omental fat rather than loss of total body weight per se. The widespread acceptance of popular low-carbohydrate high-fat diets (e.g. Atkins Diet, Zone Diet, South Beach diet) further underscores the need to evaluate dietary interventions regarding their safety and metabolic effects. These high-fat diets have been shown to be safe in the short term; however, their long-term safety has not been established. With respect to insulin sensitivity, diets enriched in saturated fats can induce insulin resistance, whereas fat substitution with monounsaturated fats can enhance insulin sensitivity. On the other hand, high-fiber, high-carbohydrate diets comprised of foods with low caloric density can similarly be used for effective weight reduction and to ameliorate insulin resistance. Although some data suggest that low-glycemic index diets are most advantageous in this regard, these effects may have more to do with increments in dietary fiber than differences in available carbohydrates. Popular low-carbohydrate, high-fat diets are being fervently embraced as an alternative to challenging modifications in lifestyle and intentional calorie reduction. Current data do not support such unbridled enthusiasm for these diets, particularly in relationship to high-fiber, high-carbohydrate diets emphasizing intake of fresh vegetables and fruits. Long-term studies

  16. Insulin resistance improves metabolic and contractile efficiency in stressed rat heart

    OpenAIRE

    Harmancey, Romain; Lam, Truong N.; Lubrano, Genna M.; Patrick H. Guthrie; Vela, Deborah; Taegtmeyer, Heinrich

    2012-01-01

    Insulin resistance is a prominent feature in heart failure, while hyperglycemia impairs cardiac contraction. We propose that decreased insulin-mediated glucose uptake by the heart preserves cardiac function in response to metabolic and hemodynamic stress. To test this hypothesis, we fed rats a high-sucrose diet (HSD). Energy substrate metabolism and cardiac work were determined ex vivo in a sequential protocol simulating metabolic and hemodynamic stress. Compared to chow-fed, control rats, HS...

  17. Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates

    OpenAIRE

    Chadderdon, Scott M.; Belcik, J. Todd; Smith, Elise; Pranger, Lindsay; Kievit, Paul; Grove, Kevin L.; Lindner, Jonathan R

    2012-01-01

    Insulin produces capillary recruitment in skeletal muscle through a nitric oxide (NO)-dependent mechanism. Capillary recruitment is blunted in obese and diabetic subjects and contributes to impaired glucose uptake. This study's objective was to define whether inactivity, in the absence of obesity, leads to impaired capillary recruitment and contributes to insulin resistance (IR). A comprehensive metabolic and vascular assessment was performed on 19 adult male rhesus macaques (Macaca mulatta) ...

  18. Fat Distribution and Insulin Resistance in Young Adult Nonobese Asian Indian Women

    OpenAIRE

    Szuszkiewicz-Garcia, Magdalene; Li, Rong; Grundy, Scott M.; Abate, Nicola; Chandalia, Manisha

    2012-01-01

    Although Asian Indian (people of Indian subcontinent descent) men are shown to have higher total and truncal body fat as well as greater insulin resistance compared to white men matched for total body fat and age, data in women are not conclusive. The objective of this study was to compare total and regional fat distribution and insulin sensitivity between healthy young premenopausal Asian Indian and white women of similar body mass index (BMI). Twenty Asian Indian women (65% immigrants and 3...

  19. Relationships between acylated ghrelin with growth hormone, insulin resistance, lipid profile, and cardio respiratory function in lean and obese men

    Directory of Open Access Journals (Sweden)

    Hasan Matin Homaee

    2011-01-01

    Conclusions: Obese and lean inactive young men had different levels of acylated ghrelin, GH, insulin, insulin resistance index, cardiorespiratory function and body fat percent. Body fat percent, insulin, and GH levels appear to be best determinant factors of acylated ghrelin levels. Also, in both obese and lean young men, higher levels of cardiovascular function were associated with higher levels of acylated ghrelin.

  20. Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats.

    Science.gov (United States)

    Han, Xiuqing; Liu, Chunhua; Xue, Yong; Wang, Jingfeng; Xue, Changhu; Yanagita, Teruyoshi; Gao, Xiang; Wang, Yuming

    2016-01-01

    We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model. PMID:26775542

  1. Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Mohamad Hafizi Abu Bakar

    2015-05-01

    Full Text Available Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.

  2. Vitamin D Deficiency in Obese Children and Its Relationship to Insulin Resistance and Adipokines

    Directory of Open Access Journals (Sweden)

    Christian L. Roth

    2011-01-01

    Full Text Available Low-serum concentrations of 25-hydroxyvitamin D [25(OHD] are associated with insulin resistance in adults. Less data are available in pediatric populations. Serum 25(OHD serum concentrations were assessed in 125 obese and 31 nonobese children (age 11.9±2.7 y, range 6–16 y, 49% male living in Bonn, Germany. The relationship between 25(OHD, measured by liquid chromatography-tandem mass spectrometry, and measures of insulin sensitivity and adipokines adiponectin and resistin were analyzed. Seventy-six % of subjects were 25(OHD deficient (<20 ng/mL. Higher insulin, homeostasis model assessment-insulin resistance (HOMA-IR r=−0.269, P=0.023, and hemoglobin A1c (HbA1c as well as lower quantitative insulin-sensitivity check index (QUICKI r=0.264, P=0.030 values were found in obese children with lower 25(OHD concentrations even after adjustment for gender, age, and body mass index. Furthermore, 25(OHD correlated significantly with adiponectin, but not with resistin. Our results suggest that hypovitaminosis D is a risk factor for developing insulin resistance independent of adiposity.

  3. Normal metabolic flexibility despite insulin resistance women with polycystic ovary syndrome.

    Science.gov (United States)

    Adamska, Agnieszka; Karczewska-Kupczewska, Monika; Nikołajuk, Agnieszka; Otziomek, Elżbieta; Górska, Maria; Kowalska, Irina; Strączkowski, Marek

    2013-01-01

    Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder, where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. Insulin resistance (IR) is connected with disturbances in switching between lipid and carbohydrate oxidation in response to insulin, called "metabolic inflexibility". The aim of the present study was to estimate the whole-body insulin sensitivity, lipid and carbohydrate oxidation, metabolic flexibility in lean and obese PCOS women. The study group consisted of 92 women with PCOS, 40 lean (BMI25 kg/m²), and 30 healthy normally menstruating women (14 lean and 16 overweight/obese) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Both the presence of PCOS (Pmetabolism. Obese women had lower glucose oxidation (P=0.005) and higher lipid oxidation (PMetabolic flexibility was impaired in the obese (P=0.001) but it was not influenced by the presence of PCOS (P=0.78). Our data indicate that PCOS women have normal metabolic flexibility, which could suggest a distinct pathophysiological mechanism for insulin resistance in this group. PMID:23801024

  4. Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose- fed rat

    Science.gov (United States)

    Metabolic syndrome is characterized by insulin resistance, dyslipidemia, and increased oxidative stress. Tea polyphenols, as both insulin potentiating factors and antioxidants, might act in preventing the metabolic syndrome. We aimed to determine the effects of green tea extract consumption on oxida...

  5. Trigonella foenum-graecum water extract improves insulin sensitivity and stimulates PPAR and γ gene expression in high fructose-fed insulin-resistant rats

    Directory of Open Access Journals (Sweden)

    Abbas Mohammadi

    2016-01-01

    Conclusion: This study demonstrates the beneficial effects of trigonella foenum-graecum extract on insulin resistance in rats fed on a high-fructose diet. At least three mechanisms are involved, including direct insulin-like effect, increase in adiponectin levels, and PPARγ protein expression.

  6. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins

    Energy Technology Data Exchange (ETDEWEB)

    Miller, L.L.

    1976-01-01

    The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs--Ringer bicarbonate buffer containing 3% bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, ..cap alpha../sub 1/-acid glycoprotein, ..cap alpha../sub 2/-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 ..mu..g) used was insufficient to induce synthesis of ..cap alpha../sub 2/-acute phase globulin, net syntheses of albumin, fibrinogen, ..cap alpha../sub 1/-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and ..cap alpha../sub 1/-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.

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

    International Nuclear Information System (INIS)

    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

  8. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

    OpenAIRE

    Bell Jimmy D; Nunn Alistair VW; Guy Geoffrey W

    2009-01-01

    Abstract The metabolic syndrome may have its origins in thriftiness, insulin resistance and one of the most ancient of all signalling systems, redox. Thriftiness results from an evolutionarily-driven propensity to minimise energy expenditure. This has to be balanced with the need to resist the oxidative stress from cellular signalling and pathogen resistance, giving rise to something we call 'redox-thriftiness'. This is based on the notion that mitochondria may be able to both amplify membran...

  9. High dietary protein intake, reducing or eliciting insulin resistance?

    NARCIS (Netherlands)

    Rietman, A.; Schwarz, J.; Tome, D.; Kok, F.J.; Mensink, M.R.

    2014-01-01

    Dietary proteins have an insulinotropic effect and thus promote insulin secretion, which indeed leads to enhanced glucose clearance from the blood. In the long term, however, a high dietary protein intake is associated with an increased risk of type 2 diabetes. Moreover, branched-chain amino acids (

  10. Autophagy: A Potential Link between Obesity and Insulin Resistance

    NARCIS (Netherlands)

    P. Codogno; A.J. Meijer

    2010-01-01

    Dysregulation of autophagy contributes to aging and to diseases such as neurodegeneration, cardiomyopathy, and cancer. The paper by Yang et al. (2010) in this issue of Cell Metabolism indicates that defective autophagy may also underlie impaired insulin sensitivity in obesity and that upregulating a

  11. [THE ROLE OF ADIPOCYTOKINES IN THE FORMATION OF INSULIN RESISTANCE IN PATIENTS WITH PRIMARY HYPOTHYROIDISM].

    Science.gov (United States)

    Vatseba, T S

    2014-01-01

    The aim of the study was to investigate the levels of adiponectin and indexes of insulin resistance in patients with primary hypothyroidism. In this article published data and personal data about the role of adiponectin in formation insulin resistance in patients with primary hypothyroidism are shown. The study involved 72 patients with primary hypothyroidism. arising on the background of endemic goiter, including 42 women and 30 men. A direct linear correlation between indexes HOMA IR and TSH was established. We found significantly lower levels of adiponectin in all patients with manifest and subclinical hypothyroidism compared with the control group. Low levels of adiponectin may be an independent factor in the development of insulin resistance in hypothyroidism, cardiovascular diseases and can be considered to be the marker of hypothyroidism with components of metabolic syndrome.

  12. 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

  13. Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats.

    Science.gov (United States)

    Guo, Lili; Shi, Mingyi; Zhang, Ling; Li, Guangzhi; Zhang, Lingxiang; Shao, Hu; Fang, Penghua; Ma, Yingping; Li, Jian; Shi, Qiaojia; Sui, Yumei

    2011-08-01

    Seeing that galanin increases animal body weight on the conditions of inhibiting insulin secretion and animals with metabolic disorder of galanin easily suffer from diabetes, we postulate that endogenous galanin is necessary to reduce insulin resistance in adipocytes. To test this hypothesis, we compared four groups of rats to examine whether an increase in galanin secretion stimulated by swimming may reduce insulin resistance. The rats from sedentary and trained drug groups were injected by M35, a galanin antagonist. The rats from trained control and trained drug groups swam after each injection for four weeks. We found that exercise significantly elevated plasma galanin contents and glucose transporter 4 (GLUT4) mRNA levels in adipocytes. Meanwhile, M35 treatment reduced GLUT4 and GLUT4 mRNA levels, and glucose infusing rates in euglycemic-hyperinsulinemic clamp tests. The ratios of GLUT4 concentrations at plasma membranes to total cell membranes in both drug groups were lower compared with each control group, respectively. These observations suggest that endogenous galanin reduces insulin resistance by increasing GLUT4 contents and promoting GLUT4 transportation from intracellular membranes to plasma membranes in adipocytes. Galanin is an important hormone to reduce insulin resistance in rats. PMID:21664358

  14. Adherence to a low-fat vs. low-carbohydrate diet differs by insulin resistance status.

    Science.gov (United States)

    McClain, A D; Otten, J J; Hekler, E B; Gardner, C D

    2013-01-01

    Previous research shows diminished weight loss success in insulin-resistant (IR) women assigned to a low-fat (LF) diet compared to those assigned to a low-carbohydrate (LC) diet. These secondary analyses examined the relationship between insulin-resistance status and dietary adherence to either a LF-diet or LC-diet among 81 free-living, overweight/obese women [age = 41.9 ± 5.7 years; body mass index (BMI) = 32.6 ± 3.6 kg/m(2)]. This study found differential adherence by insulin-resistance status only to a LF-diet, not a LC-diet. IR participants were less likely to adhere and lose weight on a LF-diet compared to insulin-sensitive (IS) participants assigned to the same diet. There were no significant differences between IR and IS participants assigned to LC-diet in relative adherence or weight loss. These results suggest that insulin resistance status may affect dietary adherence to weight loss diets, resulting in higher recidivism and diminished weight loss success of IR participants advised to follow LF-diets for weight loss.

  15. Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels

    Science.gov (United States)

    Binder, Elke; Bermúdez-Silva, Francisco J.; André, Caroline; Elie, Melissa; Romero-Zerbo, Silvana Y.; Leste-Lasserre, Thierry; Belluomo, llaria; Duchampt, Adeline; Clark, Samantha; Aubert, Agnes; Mezzullo, Marco; Fanelli, Flaminia; Pagotto, Uberto; Layé, Sophie; Mithieux, Gilles; Cota, Daniela

    2013-01-01

    Background Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed. Methodology/Principal Findings Male C57BL/6J mice were fed chow or a high-fat diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group) was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed. Conclusions/Significance These findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation is lacking in

  16. Leucine supplementation protects from insulin resistance by regulating adiposity levels.

    Directory of Open Access Journals (Sweden)

    Elke Binder

    Full Text Available BACKGROUND: Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed. METHODOLOGY/PRINCIPAL FINDINGS: Male C57BL/6J mice were fed chow or a high-fat diet (HFD, supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3 in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed. CONCLUSIONS/SIGNIFICANCE: These findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation

  17. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

    Directory of Open Access Journals (Sweden)

    Bell Jimmy D

    2009-04-01

    Full Text Available Abstract The metabolic syndrome may have its origins in thriftiness, insulin resistance and one of the most ancient of all signalling systems, redox. Thriftiness results from an evolutionarily-driven propensity to minimise energy expenditure. This has to be balanced with the need to resist the oxidative stress from cellular signalling and pathogen resistance, giving rise to something we call 'redox-thriftiness'. This is based on the notion that mitochondria may be able to both amplify membrane-derived redox growth signals as well as negatively regulate them, resulting in an increased ATP/ROS ratio. We suggest that 'redox-thriftiness' leads to insulin resistance, which has the effect of both protecting the individual cell from excessive growth/inflammatory stress, while ensuring energy is channelled to the brain, the immune system, and for storage. We also suggest that fine tuning of redox-thriftiness is achieved by hormetic (mild stress signals that stimulate mitochondrial biogenesis and resistance to oxidative stress, which improves metabolic flexibility. However, in a non-hormetic environment with excessive calories, the protective nature of this system may lead to escalating insulin resistance and rising oxidative stress due to metabolic inflexibility and mitochondrial overload. Thus, the mitochondrially-associated resistance to oxidative stress (and metabolic flexibility may determine insulin resistance. Genetically and environmentally determined mitochondrial function may define a 'tipping point' where protective insulin resistance tips over to inflammatory insulin resistance. Many hormetic factors may induce mild mitochondrial stress and biogenesis, including exercise, fasting, temperature extremes, unsaturated fats, polyphenols, alcohol, and even metformin and statins. Without hormesis, a proposed redox-thriftiness tipping point might lead to a feed forward insulin resistance cycle in the presence of excess calories. We therefore suggest

  18. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

    Science.gov (United States)

    Nunn, Alistair Vw; Bell, Jimmy D; Guy, Geoffrey W

    2009-01-01

    The metabolic syndrome may have its origins in thriftiness, insulin resistance and one of the most ancient of all signalling systems, redox. Thriftiness results from an evolutionarily-driven propensity to minimise energy expenditure. This has to be balanced with the need to resist the oxidative stress from cellular signalling and pathogen resistance, giving rise to something we call 'redox-thriftiness'. This is based on the notion that mitochondria may be able to both amplify membrane-derived redox growth signals as well as negatively regulate them, resulting in an increased ATP/ROS ratio. We suggest that 'redox-thriftiness' leads to insulin resistance, which has the effect of both protecting the individual cell from excessive growth/inflammatory stress, while ensuring energy is channelled to the brain, the immune system, and for storage. We also suggest that fine tuning of redox-thriftiness is achieved by hormetic (mild stress) signals that stimulate mitochondrial biogenesis and resistance to oxidative stress, which improves metabolic flexibility. However, in a non-hormetic environment with excessive calories, the protective nature of this system may lead to escalating insulin resistance and rising oxidative stress due to metabolic inflexibility and mitochondrial overload. Thus, the mitochondrially-associated resistance to oxidative stress (and metabolic flexibility) may determine insulin resistance. Genetically and environmentally determined mitochondrial function may define a 'tipping point' where protective insulin resistance tips over to inflammatory insulin resistance. Many hormetic factors may induce mild mitochondrial stress and biogenesis, including exercise, fasting, temperature extremes, unsaturated fats, polyphenols, alcohol, and even metformin and statins. Without hormesis, a proposed redox-thriftiness tipping point might lead to a feed forward insulin resistance cycle in the presence of excess calories. We therefore suggest that as oxidative stress

  19. Urine C-peptide creatinine ratio can be used to assess insulin resistance and insulin production in people without diabetes: an observational study

    OpenAIRE

    Oram, Richard A.; Rawlingson, Andrew; Shields, Beverley M; Bingham, Coralie; Besser, Rachel E. J.; McDonald, Tim J.; Knight, Bridget A; Hattersley, Andrew T

    2013-01-01

    Objectives The current assessment of insulin resistance (IR) in epidemiology studies relies on the blood measurement of C-peptide or insulin. A urine C-peptide creatinine ratio (UCPCR) can be posted from home unaided. It is validated against serum measures of the insulin in people with diabetes. We tested whether UCPCR could be a surrogate measure of IR by examining the correlation of UCPCR with serum insulin, C-peptide and HOMA2 (Homeostasis Model Assessment 2)-IR in participants without dia...

  20. Impact of Adiposity on Incident Hypertension Is Modified by Insulin Resistance in Adults: Longitudinal Observation From the Bogalusa Heart Study.

    Science.gov (United States)

    Zhang, Tao; Zhang, Huijie; Li, Shengxu; Li, Ying; Liu, Yaozhong; Fernandez, Camilo; Harville, Emily; Bazzano, Lydia; He, Jiang; Chen, Wei

    2016-01-01

    Adiposity and insulin resistance are closely associated with hypertension. This study aims to investigate whether the association between adiposity and hypertension is modified by insulin resistance. The cohort consisted of 1624 middle-aged normotensive black and white adults aged 18 to 43 years at baseline who followed for 16 years on average. Overweight/obesity at baseline was defined as body mass index (BMI) ≥25, and insulin resistance was measured using homeostasis model assessment of insulin resistance. Prevalence of incident hypertension was compared between the insulin-sensitive adiposity and insulin-resistant adiposity groups. The prevalence of incident hypertension was higher in the insulin-resistant adiposity than in the insulin-sensitive adiposity group (32.1% versus 22.1%, Pobesity was associated with incident hypertension (odds ratio, 1.9; P=0.008). Odds ratios did not differ between blacks and whites (P=0.238). Of note, the odds ratios of BMI associated with hypertension significantly increased with increasing quartiles of baseline homeostasis model assessment (odds ratio, 1.3, 1.1, 1.5, and 2.5 in quartiles I, II, III, and IV, respectively; P=0.006 for trend). Slopes of increasing follow-up blood pressure with baseline BMI, measured as regression coefficients (β), were significantly greater in insulin-resistant than in insulin-sensitive individuals (β=0.74 versus β=0.35 for systolic blood pressure, P=0.004 for difference; β=0.51 versus β=0.23 for diastolic blood pressure, P=0.001 for difference). These findings suggest that insulin resistance has a synergistic effect on the obesity-hypertension association in young adults, indicating that the role of adiposity in the development of hypertension is modified by insulin resistance.

  1. Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Buhl, Esben Selmer; Jessen, Niels; Pold, Rasmus;

    2002-01-01

    The insulin resistance syndrome is characterized by several risk factors for cardiovascular disease. Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action...... treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles. Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces......, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat. Furthermore, acute AICAR exposure has been found to reduce sterol and fatty acid synthesis in rat hepatocytes incubated in vitro as well as suppress endogenous glucose production in rats under euglycemic...

  2. Evaluation of organ-specific glucose metabolism by 18F-FDG in insulin receptor substrate-1 (IRS-1) knockout mice as a model of insulin resistance

    International Nuclear Information System (INIS)

    Insulin resistance (IR) is a physiological condition in which the body produces insulin but does not result in a sufficient biological effect. Insulin resistance is usually asymptomatic but is associated with health problems and is a factor in the metabolic syndrome. The aim of the present study is to clarify organ-specific insulin resistance in normal daily conditions using [18F]-2-fluoro-2-deoxy-D-glucose ([18F]-FDG). The biodistribution of [18F]-FDG was examined in insulin receptor substrate-1 (IRS-1) knockout mice, an animal model of skeletal muscle insulin resistance, and C57BL/6J (wild-type) mice with and without insulin loading. Mice received 0.5 MBq of [18F]-FDG injected into the tail vein, immediately followed by nothing (control cohorts) or an intraperitoneal injection of 1.5 mU/g body weight of human insulin as an insulin loading test. Blood glucose concentrations for all of the experimental animals were assessed at 0, 20, 40, and 60 min post-injection. The mice were subsequently killed, and tissue was collected for evaluation of [18F]-FDG biodistribution. The radioactivity of each organ was measured using a gamma counter. In the absence of insulin, the blood glucose concentrations of wild-type mice (132±26 mg/dl) and IRS-1 knockout mice (134±18 mg/dl) were not significantly different. Blood glucose concentrations decreased following insulin administration, with lower concentrations in wild-type mice than in knockout mice at 20, 40, and 60 min. A statistically significant difference in [18F]-FDG uptake between wild-type mice and IRS-1 knockout mice was confirmed in the heart, abdominal muscle, and femoral muscle. With insulin loading, [18F]-FDG uptake in the heart, back muscle, and abdominal muscle was significantly increased compared to without insulin loading in both wild-type mice and knockout mice. Our results showed that IR significantly affected [18F]-FDG uptake in the heart in normal daily conditions. IR was associated with decreased [18F

  3. Skeletal muscle mitochondrial bioenergetics and morphology in high fat diet induced obesity and insulin resistance: focus on dietary fat source

    Directory of Open Access Journals (Sweden)

    Rosalba ePutti

    2016-01-01

    Full Text Available It has been suggested that skeletal muscle mitochondria play a key role in high fat diet induced insulin resistance. Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle insulin resistance. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to insulin resistance. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of insulin resistance. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift towards mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and insulin resistance development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle insulin resistance and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle insulin resistance, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance.

  4. Gender difference and relationship of insulin resistance with microalbuminuria type-2 diabetes

    International Nuclear Information System (INIS)

    To determine the relationship of insulin resistance with microalbuminuria in patients of type-2 Diabetes mellitus and observe gender difference if any. Study Design: A cross-sectional study. Place and Duration of Study: Diabetes Clinic of Combined Military Hospital, Malir Cantt, from April to August 2007. Methodology: One hundred and fifty five patients of type-2 Diabetes mellitus were included in the study who had either microalbuminuria or normo albuminuria. Body mass index, waist circumference and blood pressure were recorded. Fasting venous blood sample was collected for plasma glucose (FPG), serum insulin, total and HDL cholesterol, triglycerides, creatinine and HbA1c. Urine albumin excretion was determined using urine albumin to creatinine ratio. Insulin resistance was calculated from fasting plasma glucose and serum insulin levels, using homeostatic model assessment of insulin resistance (HOMA-IR). Correlation and association testing was carried out with significance at p < 0.05. Results: Microalbuminuria was found to be significantly correlated with HOMA-IR (r = 0.33, p < 0.001), serum insulin (r = 0.28, p = < 0.001), body mass index (r = 0.18, p = 0.02) and waist circumference (r = 0.21, p = 0.008). This correlation was more significant in women (n = 85, r = 0.48, p = < 0.0001) as compared to men (n = 70, r = 0.14, p = 0.12). The correlation between HOMA-IR and urine albumin excretion remained highly significant (p = 0.001) after controlling for gender, age, duration of diabetes, waist circumference, hypertension, triglycerides and HbA1c. Conclusion: Urinary albumin excretion in patients of type-2 diabetes is strongly associated with insulin resistance and related cardiovascular risk factors. This association appears to be stronger in women than the men, in our population. (author)

  5. ANTIDIABETIC AND HYPOLIPIDEMIC ACTIVITY OF GYMNEMA SYLVESTRE IN DEXAMETHASONE INDUCED INSULIN RESISTANCE IN ALBINO RATS

    Directory of Open Access Journals (Sweden)

    Hemanth Kumar V, Nagendra Nayak IM , Shobha V Huilgol, Saeed M Yendigeri , Narendar K

    2015-07-01

    Full Text Available Background: Gymnema sylvestre plant was widely used for medicinal purpose. The plant leaves were traditionally used to treat diabetes. Aim: To determine the antidiabetic and hypolipidemic activity of Gymnema sylvestre in dexamethasone induced insulin resistance in Albino rats. Objectives: The present study was undertaken to evaluate antidiabetic and hypolipidemic activity of Gymnema sylvestre leaf aqueous extract against dexamethasone induced insulin resistance in Albino rats. Materials and Methods: Animals were divided into five groups. Normal control and diabetic control group received gum acacia (2% orally for 12days, and normal saline (i.p., dexamethasone (8mg/kg/i.p. from day 7- day12 respectively. Two test groups (Gymnema sylvestre leaf aqueous extract 2 and 4gm/kg/p.o./12days and standard control received metformin (2gm/kg/p.o./12 days. The two test groups, standard control group received dexamethasone (8mg/kg/i.p from day 7- day 12 respectively. The antidiabetic and hypolipidemic activity was estimated by measuring serum glucose, insulin, lipid levels and histopathological evaluation of liver tissue. Results were analyzed by using one way ANOVA followed by Scheffe’s multiple comparison test. Results: Treatment with aqueous extract of Gymnema sylvestre (2 and 4gm/kg/p.o significantly (p<0.01 altered the elevated glucose, lipid, insulin levels and also improved the histopathology of liver in dexamethasone induced insulin resistance rats. Conclusion: Treatment with aqueous extract of Gymnema sylvestre improved the altered glucose, insulin and lipid profile in insulin resistance rats.

  6. Steatosis and insulin resistance in hepatitis C: A way out for the virus?

    Institute of Scientific and Technical Information of China (English)

    José A Del Campo; Manuel Romero-Gómez

    2009-01-01

    The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas metabolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expression and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activated receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an efficient mechanism for stable viral replication. Chronic HCV infection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and impairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signalling by genotype-specific mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3a and mammalian target of rapamycin (mTOR) in genotype 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with fibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.

  7. Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women

    OpenAIRE

    Petri Wiklund; Xiaobo Zhang; Satu Pekkala; Reija Autio; Lingjia Kong; Yifan Yang; Sirkka Keinänen-Kiukaanniemi; Markku Alen; Sulin Cheng

    2016-01-01

    Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectr...

  8. Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle

    OpenAIRE

    Jason K Kim; Gimeno, Ruth E.; Higashimori, Takamasa; Kim, Hyo-Jeong; Choi, Hyejeong; Punreddy, Sandhya; Mozell, Robin L.; TAN, GUO; Stricker-Krongrad, Alain; Hirsch, David J.; Fillmore, Jonathan J.; Liu, Zhen-Xiang; Dong, Jianying; Cline, Gary; Stahl, Andreas

    2004-01-01

    Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid transport protein 1 (FATP1) is an acyl-CoA synthetase highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism by converting fatty acids into fatty acyl-CoA. To investigate the role of FATP1 in glucose homeostasis and in the pathogenesis of insulin resistance, we examined the e...

  9. Study of the expression of apelin and its recoptor in ischemic myocardium in insulin-resistant rats

    Institute of Scientific and Technical Information of China (English)

    魏芳晶

    2013-01-01

    Objective To investigate the expression of apelin and its recoptor (APJ) in myocardium in insulin-resistant CIR rats with myocardial ischemia.Methods Totally 24male SD rats were randomly divided into three groups:IR group,IR+ischemia group,the control group (n=8each) .Rats in IR and IR+ischemia groups were fed with the high fat diet.Rats in control group were given the basic diet.The rat model of insulin resistance was assessed by fasting blood glucose (FBG) ,fasting insulin (Fins) and insulin resistance index (HOMA-IR) .The

  10. Immunohistochemistry pattern of hepatic inflammatory and insulin resistance markers in experimental model of nonalcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Mônica Souza de Miranda Henriques

    2014-04-01

    Full Text Available Introduction:The pathophysiology of nonalcoholic steatohepatitis (NAS includes, basically, insulin resistance, inflammation and oxidative stress. Thus, a study of immunostaining for liver insulin, adiponectin, tumor necrosis factor alpha (TNF-α, and inducible nitric oxide synthase (iNOS receptors was conducted.Objective:To expand the knowledge about the pathophysiological and molecular mechanisms underlying the experimental model of steatohepatitis in rats fed a high-fat diet.Method:Twenty Wistar rats were divided into two groups: G1 (control, fed a standard diet, and G2 (fed a high-fat diet containing 58% of energy derived from fat, 18% from protein and 24% from carbohydrate. After eight weeks the animals were sacrificed. Blood glucose, insulin, total cholesterol, high-density lipoprotein (HDL, the very low-density lipoproteins (VLDL, triglycerides, aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP and gamma-glutamyl transferase (GGT were determined. The liver tissue was submitted to histopathological analysis, using a NAS score. In immunohistochemistry, we studied the expression of the insulin receptor, adiponectin, TNF-α and iNOS by tissue microarray method.Results and conclusion:There was marked cytoplasmic immunostaining for TNF-α and iNOS mediators in the group on a fat diet. Regarding insulin and adiponectin molecular markers, a reduction of cytoplasmic immunoreactivity of these antigens was observed in the group on a fat diet, reflecting, respectively, the state of hepatocellular inflammation (steatohepatitis and insulin resistance in this experimental model of fat liver disease.

  11. Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats

    DEFF Research Database (Denmark)

    Brandt, Nina; De Bock, Katrien; Richter, Erik;

    2010-01-01

    counteracted by training. In the perfused hindlimb, insulin-stimulated glucose transport in red gastrocnemius muscle was completely abolished in CAF and rescued by exercise training. Apart from a tendency toward an approximately 20% reduction in both basal and insulin-stimulated Akt Ser(473) phosphorylation (P......) among the groups. In conclusion, surplus energy intake of a palatable but low-fat cafeteria diet resulted in obesity and insulin resistance that was rescued by exercise training. Interestingly, insulin resistance was not accompanied by major defects in the insulin-signaling cascade or in altered AMPK......Excess energy intake via a palatable low-fat diet (cafeteria diet) is known to induce obesity and glucose intolerance in rats. However, the molecular mechanisms behind this adaptation are not known, and it is also not known whether exercise training can reverse it. Male Wistar rats were assigned to...

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

    OpenAIRE

    You Lim Kim; Tae Kyun Kim; Eun Sun Cheong; Dong Geum Shin; Gyu Sik Choi; Jihye Jung; Kyung-Ah Han; Kyung Wan Min

    2012-01-01

    Background Central 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. Methods Total of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma gluc...

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

    OpenAIRE

    Kim, Mi-Hyun; Bae, Yun-Jung

    2015-01-01

    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 Insuli...

  14. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    OpenAIRE

    C-W. Wu; Biggar, K.K.; Storey, K.B.

    2013-01-01

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of ...

  15. Prevention of insulin resistance with Hibiscus sabdariffa Linn. extract in high-fructose fed rat

    OpenAIRE

    Trinovita Andraini; Sophie Yolanda

    2015-01-01

    Background: Dyslipidemia and stress oxidative play an important role as the cause of insulin resistance. One herb that has potent antioxidant effect and may improve dyslipidemia is Hibiscus sabdariffa Linn. The aim of this study was to evaluate the effect of Hibiscus sabdariffa Linn. extract on fasting blood glucose level, fasting blood insulin level, and insulin resistance index (HOMA-IR) in high-fructose fed rat.Methods: This was an experimental study in 25 Sprague-Dawley rats which were ad...

  16. Insulin resistance as a physiological defense against metabolic stress

    DEFF Research Database (Denmark)

    Nolan, Christopher J; Ruderman, Neil B; Kahn, Steven E;

    2015-01-01

    Stratifying the management of type 2 diabetes (T2D) has to take into account marked variability in patient phenotype due to heterogeneity in its pathophysiology, different stages of the disease process, and multiple other patient factors including comorbidities. The focus here is on the very...... to the body and should be counteracted at any cost. Instead we propose that IR, particularly in this high-risk subgroup, is a defense mechanism that protects critical tissues of the cardiovascular system from nutrient-induced injury. Overriding IR in an effort to lower plasma glucose levels, particularly...... with intensive insulin therapy, could therefore be harmful. Treatments that nutrient off-load to lower glucose are more likely to be beneficial. The concepts of "IR as an adaptive defense mechanism" and "insulin-induced metabolic stress" may provide explanation for some of the unexpected outcomes of recent major...

  17. Leucine supplementation protects from insulin resistance by regulating adiposity levels

    OpenAIRE

    Elke Binder; Bermúdez-Silva, Francisco J.; Caroline André; Melissa Elie; Romero-Zerbo, Silvana Y.; Thierry Leste-Lasserre; Ilaria Belluomo; Adeline Duchampt; Samantha Clark; Agnes Aubert; Marco Mezzullo; Flaminia Fanelli; Uberto Pagotto; Sophie Layé; Gilles Mithieux, &

    2013-01-01

    Background[br/] Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed.[br/] [br/] Methodology/Principal Findings[br/] Male C57BL/6J mice were fed chow or a high-fat diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD-fed...

  18. Inflamed macrophage microvesicles induce insulin resistance in human adipocytes

    OpenAIRE

    Zhang, Yaqin; Shi, Li; Mei, Hongliang; Zhang, Jiexin; Zhu, Yunxia; Han, Xiao; Zhu, Dalong

    2015-01-01

    Background Cytokines secreted by adipose tissue macrophages (ATMs) significantly alter adipocyte function, inducing inflammatory responses and decreasing insulin sensitivity. However, little relevant information is available regarding the role of microvesicles (MVs) derived from ATMs in macrophage-adipocyte crosstalk. Methods MVs were generated by stimulation of M1 or M2 phenotype THP-1 macrophages and incubated with human primary mature adipocytes and differentiated adipocytes. Subsequently,...

  19. Insulin Resistance and Increased Muscle Cytokine Levels in Patients With Mitochondrial Myopathy

    DEFF Research Database (Denmark)

    Rue, Nana; Vissing, John; Galbo, Henrik

    2014-01-01

    CONTEXT: Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production. OBJECTIVE: The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle. DESIGN......: The intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed. MAIN OUTCOME MEASURES: Glucose infusion rate during 90-120 minutes of insulin infusion...... was measured. Cytokine concentrations in dialysate were also measured. RESULTS: Muscle strength, percentage fat mass, and creatine kinase in plasma did not differ between groups. The maximal oxygen uptake was 21 ± 3 (SE) (P) and 36 ± 3(C) mL/kg·min (2P insulin, C-peptide, and glucagon were higher...

  20. Insulin resistance, dyslipidemia, and apolipoprotein E interactions as mechanisms in cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Salameh, Therese S; Rhea, Elizabeth M; Banks, William A; Hanson, Angela J

    2016-09-01

    An increased risk for Alzheimer's disease is associated with dyslipidemia and insulin resistance. A separate literature shows the genetic risk for developing Alzheimer's disease is strongly correlated to the presence of the E4 isoform of the apolipoprotein E carrier protein. Understanding how apolipoprotein E carrier protein, lipids, amyloid β peptides, glucose, central nervous system insulin, and peripheral insulin interact with one another in Alzheimer's disease is an area of increasing interest. Here, we will review the evidence relating apolipoprotein E carrier protein, lipids, and insulin action to Alzheimer's disease and Aβ peptides and then propose mechanisms as to how these factors might interact with one another to impair cognition and promote Alzheimer's disease. PMID:27470930