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Sample records for acute insulin resistance

  1. Acute pain induces insulin resistance in humans

    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...... randomly sequenced hyperinsulinemic–euglycemic (insulin infusion rate, 0.6 mU · kg-1 · min-1 for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0–10, just before...... the clamp procedure (study P). In the other study, no pain was inflicted (study C). Results: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37 ± 1.87 mg · kg-1 · min-1 (mean ± SD) in study C to 4.97 ± 1.38 mg · kg-1 · min-1 in study P (P

  2. Lipoprotein Ratios as Surrogate Markers for Insulin Resistance in South Indians with Normoglycemic Nondiabetic Acute Coronary Syndrome

    Medha Rajappa; M. G. Sridhar; Balachander, J; Sethuraman, K. R.; Kalai Selvi Rajendiran

    2014-01-01

    Background. Insulin resistance has been associated with dyslipidemia and cardiovascular disease. Even though homeostasis model assessment of insulin resistance (HOMA-IR) is a well-known insulin resistance predictor, estimation of serum lipoprotein ratios has been recently suggested as a surrogate marker for insulin resistance. Here, we evaluated the relationship between lipoprotein ratios and insulin resistance in normoglycemic nondiabetic south Indians with acute coronary syndrome. Methods. ...

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

    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.

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

    Sayantan Ray; Ashit Kumar Bairagi; Santanu Guha; Satyabrata Ganguly; Debes Ray; Ashis Kumar Basu; Anirban Sinha

    2012-01-01

    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 an...

  5. Study on the phenomenon of insulin resistance (IR) in patients with acute cerebral infarction

    Objective: To investigate the presence of insulin resistance (IR) in patients with cerebral infarction and the indication for insulin therapy. Methods: Fasting blood glucose (FPG) (with biochemistry), fasting serum insulin (FINS) and cortisol (with RIA) levels were measured in 50 patients with cerebral infarction and 80 controls. Insulin sensitivity index (ISI) was calculated and correlation with the score of neurologic impairment as well as the size of lesion was studied. Results: FPG, FINS and cortisol levels in the patients were significantly higher than those in the controls (P<0.001 ) while the ISI was significantly lower (P <0.001 ) than that in the controls. Levels of there parameters were significantly higher in patients with moderate-severe lesions than those in patients with only mild lesion (P<0.001, P<0.01, P<0.05 respectively). ISI was negatively correlated to the size of infarction (r=-0.313, P<0.05) and also to the score of neurologic impairment (r=-0.317, P<0.05). The mortality and morbidity in the moderate severe group were naturally higher than those in the mild group. Conclusion: Insulin resistance does exist during the acute stage of cerebral infarction. Degree of hyperinsulinaemia and severity of the resistance are related to the course and prognosis of the disease process. Insulin therapy should be considered in those patients with hyperglycemia. (authors)

  6. Lipoprotein ratios as surrogate markers for insulin resistance in South indians with normoglycemic nondiabetic acute coronary syndrome.

    Rajappa, Medha; Sridhar, M G; Balachander, J; Sethuraman, K R; Rajendiran, Kalai Selvi

    2014-01-01

    Background. Insulin resistance has been associated with dyslipidemia and cardiovascular disease. Even though homeostasis model assessment of insulin resistance (HOMA-IR) is a well-known insulin resistance predictor, estimation of serum lipoprotein ratios has been recently suggested as a surrogate marker for insulin resistance. Here, we evaluated the relationship between lipoprotein ratios and insulin resistance in normoglycemic nondiabetic south Indians with acute coronary syndrome. Methods. 100 normoglycemic nondiabetic ACS patients and 140 controls were enrolled in the study. Levels of fasting glucose, fasting insulin, and lipid profile [total cholesterol (TC), triglycerides (TG), and high density lipoprotein cholesterol (HDL-C)], lipoprotein(a) [Lp(a)] levels were measured and lipoprotein ratios were computed. HOMA-IR was used to calculate the insulin resistance. Receiver operating characteristic curves (ROC) analysis was used to compare the power of these lipoprotein ratios to predict insulin resistance. Results. Lipoprotein ratios were significantly higher in normoglycemic nondiabetic ACS patients, as compared to healthy controls, and were significantly correlated with HOMA-IR by Spearman's rank correlation analysis. ROC curve showed that Lp(a)/HDL-C and TG/HDL-C ratios were the best surrogate predictors of insulin resistance in normoglycemic nondiabetic ACS. Conclusion. This study demonstrates that serum lipoprotein ratios significantly correlate with insulin resistance in normoglycemic nondiabetic ACS. Lp(a)/HDL-C and TG/HDL-C ratios could be used as surrogate markers of insulin resistance in atherosclerosis-prone south Indians with normoglycemic nondiabetic ACS. PMID:24959351

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

    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.

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

    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......, but not rapamycin reduced insulin-stimulated glucose uptake into incubated muscles, despite normal GLUT4 translocation in muscle cells. AZD8055 inhibited glycolysis in MEF cells. Abrogation of mTORC2 activity by SIN1 deletion impaired glycolysis and AZD8055 had no effect in SIN1 KO MEFs. Re-expression of wildtype...

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

    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......, but not rapamycin reduced insulin-stimulated glucose uptake into incubated muscles, despite normal GLUT4 translocation in muscle cells. AZD8055 inhibited glycolysis in MEF cells. Abrogation of mTORC2 activity by SIN1 deletion impaired glycolysis and AZD8055 had no effect in SIN1 KO MEFs. Re-expression of wildtype...

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

    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)

  11. Insulin Resistance and Prediabetes

    ... 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, ...

  12. Serum lipoprotein ratios as markers of insulin resistance: A study among non-diabetic acute coronary syndrome patients with impaired fasting glucose

    Ray, S.; Talukdar, A.; Sonthalia, N.; Saha, M.; Kundu, S.; D Khanra; Guha, S.; Basu, A. K.; Mukherjee, A.; Ray, D.; Ganguly, S.

    2015-01-01

    Background & objectives: Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS) patients. ...

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

    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.

  14. Glycosphingolipids and insulin resistance

    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

  15. Insulin Resistance and Hyperinsulinemia

    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...

  16. Insulin Resistance of Puberty.

    Kelsey, Megan M; Zeitler, Philip S

    2016-07-01

    Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity. PMID:27179965

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

    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.

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

    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

  19. Serum lipoprotein ratios as markers of insulin resistance: A study among non-diabetic acute coronary syndrome patients with impaired fasting glucose

    S Ray

    2015-01-01

    Full Text Available Background & objectives: Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS patients. Methods: Ninety non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. At the time of admission fasting glucose and insulin concentrations were measured. The homeostatic model assessment-insulin resistance (HOMA-IR was used for insulin resistance. The fasting serum total cholesterol (TC, triglycerides (TG and high density lipoprotein cholesterol (HDL-C levels were checked, and then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves (AUC of the receiver operating characteristic (ROC curves were used to compare the power of these serum lipoprotein ratios as markers. Results: Lipoprotein ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared to patients with index <2.5 (P < 0.05. Both TG/HDL-C and TC/HDL-C ratios were significantly correlated with HOMA-IR (P<0.05. The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95% CI, 0.67 to 0.93, 0.78 (95% CI, 0.65 to 0.91, respectively. Interpretation & conclusions: The findings of this study demonstrate that serum lipoprotein ratios can provide a simple means of identifying insulin resistance and can be used as markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

  20. Insulin Resistance and Hypertension

    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.

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

    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

  2. Molecular mechanism of insulin resistance

    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.

  3. Adipokines and Hepatic Insulin Resistance

    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...

  4. Insulin resistance and hepatitis C

    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.

  5. Nutritional Modulation of Insulin Resistance

    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...

  6. Adipocyte lipolysis and insulin resistance.

    Morigny, Pauline; Houssier, Marianne; Mouisel, Etienne; Langin, Dominique

    2016-06-01

    Obesity-induced insulin resistance is a major risk factor for the development of type 2 diabetes. Basal fat cell lipolysis (i.e., fat cell triacylglycerol breakdown into fatty acids and glycerol in the absence of stimulatory factors) is elevated during obesity and is closely associated with insulin resistance. Inhibition of adipocyte lipolysis may therefore be a promising therapeutic strategy for treating insulin resistance and preventing obesity-associated type 2 diabetes. In this review, we explore the relationship between adipose lipolysis and insulin sensitivity. After providing an overview of the components of fat cell lipolytic machinery, we describe the hypotheses that may support the causality between lipolysis and insulin resistance. Excessive circulating fatty acids may ectopically accumulate in insulin-sensitive tissues and impair insulin action. Increased basal lipolysis may also modify the secretory profile of adipose tissue, influencing whole body insulin sensitivity. Finally, excessive fatty acid release may also worsen adipose tissue inflammation, a well-known parameter contributing to insulin resistance. Partial genetic or pharmacologic inhibition of fat cell lipases in mice as well as short term clinical trials using antilipolytic drugs in humans support the benefit of fat cell lipolysis inhibition on systemic insulin sensitivity and glucose metabolism, which occurs without an increase of fat mass. Modulation of fatty acid fluxes and, putatively, of fat cell secretory pattern may explain the amelioration of insulin sensitivity whereas changes in adipose tissue immune response do not seem involved. PMID:26542285

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

    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...

  8. Insulin Resistance and Prediabetes

    ... 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 ...

  9. Insulin Resistance and Prediabetes

    ... 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, ...

  10. Treatment of insulin resistance in uremia.

    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. Nutritional Modulation of Insulin Resistance

    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.

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

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

    2013-01-01

    fed mice. In humans, insulin-stimulated PAK-activation was decreased in both acute insulin resistant (intralipid infusion) and in chronic insulin resistant states (obesity and diabetes). These findings show that Rac1 is a regulator of insulin-stimulated glucose uptake and a novel candidate involved in...

  13. Insulin resistance: β-arrestin development

    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.

  14. Mitochondrial efficiency and insulin resistance.

    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

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

    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. Microvascular Recruitment in Insulin Resistance

    Sjøberg, Kim Anker

    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...... 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...

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

    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...

  18. Insulin resistance and Alzheimer’s disease

    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...

  19. Role of Mitochondrial Dysfunction in Insulin Resistance

    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...

  20. Pathogenesis of Insulin Resistance in Skeletal Muscle

    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.

  1. SIRT2 regulates insulin sensitivity in insulin resistant neuronal cells.

    Arora, Amita; Dey, Chinmoy Sankar

    2016-06-10

    Insulin resistance in brain is well-associated with pathophysiology of deficits in whole-body energy metabolism, neurodegenerative diseases etc. Among the seven sirtuins, SIRT2 is the major deacetylase expressed in brain. Inhibition of SIRT2 confers neuroprotection in case of Parkinson's disease (PD) and Huntington's disease (HD). However, the role of this sirtuin in neuronal insulin resistance is not known. In this study, we report the role of SIRT2 in regulating insulin-sensitivity in neuronal cells in vitro. Using approaches like pharmacological inhibition of SIRT2, siRNA mediated SIRT2 knockdown and over-expression of wild-type and catalytically-mutated SIRT2, we observed that downregulation of SIRT2 ameliorated the reduced activity of AKT and increased insulin-stimulated glucose uptake in insulin resistant neuro-2a cells. The data was supported by over expression of catalytically-inactive SIRT2 in insulin-resistant human SH-SY5Y neuronal cells. Data highlights a crucial role of SIRT2 in regulation of neuronal insulin sensitivity under insulin resistant condition. PMID:27163642

  2. Adipose Inflammation, Insulin Resistance, and Cardiovascular Disease

    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...

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

    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...

  4. Angiotensin and insulin resistance: conspiracy theory.

    Townsend, Raymond R

    2003-04-01

    Resistance to the metabolic effects of insulin is a contender for the short list of major cardiovascular risk factors. Since the elements of the syndrome of insulin resistance were first articulated together in 1988, numerous epidemiologic investigations and treatment endeavors have established a relationship between the metabolic disarray of impaired insulin action and cardiovascular disease. Angiotensin II, the primary effector of the renin-angiotensin system, has also achieved a place in the chronicles of cardiovascular risk factors. Conspiracy mechanisms by which angiotensin II and insulin resistance interact in the pathogenesis of cardiovascular disease are reviewed, with particular attention to recent developments in this engaging area of human research. PMID:12642009

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

    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.

  6. Insulin resistance and maximal oxygen uptake

    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....

  7. Insulin resistance and diabetes in HIV infection.

    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

  8. LINK BETWEEN OXIDATIVE STRESS AND INSULIN RESISTANCE

    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.

  9. Selective insulin resistance in hepatocyte senescence

    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. Selective insulin resistance in hepatocyte senescence

    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.

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

    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

  12. A novel surrogate index for hepatic insulin resistance.

    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.

  13. Ghrelin- and GH-induced insulin resistance

    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....

  14. [The polycystic ovary syndrome and insulin resistance].

    Kreze, A; Hrnciar, J; Dobáková, M; Pekarová, E

    1997-10-01

    The insulin resistance syndrome and the polycystic ovary syndrome (PCOS) appear to have some following coincidences: the existence of subclinical acanthosis nigricans in PCOS hyperinsulinemic women, correlation of insulin levels and free testosterone, insulin-like growth factor I binding protein (IGFIBP), and sex-hormone binding globulin. Insulin and IGFI act synergically with luteinizing hormone increasing the activity of cytochrome P450c17 and its enzymatic activity in the adrenals. The decrease in IGFI level and IGFI receptors in the ovarian granulosa cells reduce the steroids aromatisation. The increased expression of IGFI receptors in the theca cells favours the androgens' synthesis. Long-term insulin therapy results in an increase in ovary volume and the blood androgens levels. The deterioration of insulin resistance in PSOC women progresses also by the reduction of type I of skeletal muscle fibres which are sensitive to insulin, and the increase of type II fibres which are resistant to insulin in hyperandrogenemia. Testosterone deteriorates the skeletal as well as hepatic insulin sensitivity by both its facilitating effect on lipolysis and the increase of free fatty acids. Abdominal obesity seen in PCOS and insulin resistance is composed by adipocytes with glucocorticoid receptors, which after cortisol stimulation activate the lipoprotein lipase and fat accumulation. Gynoid obesity with the preferential aromatisation of steroids is not evolved because of the low estrogens and progesterone levels in PCOS. Low progesterone levels (with anticortisol effect) support the development of abdominal obesity. Ultimately, the early peak of insulin secretion (4-8 min) in PCOS is higher. This fact should testify a certain diabetic disposition. (Ref. 37.) PMID:9490171

  15. Mechanisms Linking Inflammation to Insulin Resistance

    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.

  16. Anthropometric indicators of insulin resistance.

    Vasques, Ana Carolina; Rosado, Lina; Rosado, Gilberto; Ribeiro, Rita de Cassia; Franceschini, Sylvia; Geloneze, Bruno

    2010-07-01

    Some studies have analyzed the efficacy of anthropometric indicators in predicting insulin resistance (IR), for they are more economic and accessible. In this study, the objective was to discuss the measures and anthropometric indices that have been associated with IR. A bibliographic review was done, based on Scielo, Science Direct and Pubmed. Among these studies, waist and sagittal abdominal diameter presented better predictive capacity for IR, with more consistent results. The waist-to-thigh, waist-to-size, neck-to-thigh ratios, the conicity and the sagittal index have showed positive results; nevertheless, more studies are necessary to consolidate them as predictors to IR. The obtained results, with the use of body mass index and of the waist-to-hip ratio, were inconsistent. In the Brazilian population, the realization of studies evaluating the performance of these indicators in predicting IR is suggested, since the results of the studies conducted in other populations are not always applicable to ours, due to ethnic differences resulting from the great miscegenation in the country. PMID:20694396

  17. Managing insulin resistance: role of liraglutide

    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...

  18. Hypoadiponectinemia in Obesity: Association with Insulin Resistance

    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...

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

    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...

  20. Nonalcoholic steatohepatitis and insulin resistance in children

    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.

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

    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. Patients with psoriasis are insulin resistant

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

    2015-01-01

    differences between groups in plasma glucose, insulin, C-peptide, and glucagon during the clamp. LIMITATIONS: The classic hyperinsulinemic euglycemic clamp technique does not allow assessment of endogenous glucose production. CONCLUSION: Patients with psoriasis were more insulin resistant compared with...... 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......-hour hyperinsulinemic euglycemic clamps were performed in 16 patients with moderate to severe, untreated psoriasis and 16 matched control subjects. RESULTS: The 2 groups were similar with regard to age, gender, body mass index, body composition, physical activity, fasting plasma glucose, and glycosylated hemoglobin...

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

    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...

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

    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...

  5. Insulin resistance, steatosis and hepatitis C virus

    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...

  6. Advances in TCM Research of Insulin Resistance

    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.

  7. Acrolein metabolites, diabetes and insulin resistance.

    Feroe, Aliya G; Attanasio, Roberta; Scinicariello, Franco

    2016-07-01

    Acrolein is a dietary and environmental pollutant that has been associated in vitro to dysregulate glucose transport. We investigated the association of urinary acrolein metabolites N-acetyl-S-(3-hydroxypropyl)-l-cysteine (3-HPMA) and N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) and their molar sum (∑acrolein) with diabetes using data from investigated 2027 adults who participated in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). After excluding participants taking insulin or other diabetes medication we, further, investigated the association of the compounds with insulin resistance (n=850), as a categorical outcome expressed by the homeostatic model assessment (HOMA-IR>2.6). As secondary analyses, we investigated the association of the compounds with HOMA-IR, HOMA-β, fasting insulin and fasting plasma glucose. The analyses were performed using urinary creatinine as independent variable in the models, and, as sensitivity analyses, the compounds were used as creatinine corrected variables. Diabetes as well as insulin resistance (defined as HOMA-IR>2.6) were positively associated with the 3-HPMA, CEMA and ∑Acrolein with evidence of a dose-response relationship (p<0.05). The highest 3rd and 4th quartiles of CEMA compared to the lowest quartile were significantly associated with higher HOMA-IR, HOMA-β and fasting insulin with a dose-response relationship. The highest 3rd quartile of 3-HPMA and ∑Acrolein were positively and significantly associated with HOMA-IR, HOMA-β and fasting insulin. These results suggest a need of further studies to fully understand the implications of acrolein with type 2 diabetes and insulin. PMID:26991531

  8. Adipokines mediate inflammation and insulin resistance

    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.

  9. Molecular Mechanisms of Insulin Resistance Development

    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.

  10. Insulin resistance alters islet morphology in nondiabetic humans

    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...

  11. A new antihypertensive drug ameliorates insulin resistance

    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.

  12. Relationship between adiponectin, obesity and insulin resistance

    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.

  13. South Asian diets and insulin resistance.

    Misra, Anoop; Khurana, Lokesh; Isharwal, Sumit; Bhardwaj, Swati

    2009-02-01

    A role of dietary nutrients in relation to insulin resistance has been suggested but conclusive evidence in human beings is lacking. Asian Indians and South Asians are prone to develop insulin resistance and the metabolic syndrome. In the present paper, data pertaining to nutrient intake, insulin resistance and cardiovascular risk factors in Asian Indians and South Asians have been reviewed. In these populations, several dietary imbalances have been reported: low intake of MUFA, n-3 PUFA and fibre, and high intake of fats, saturated fats, carbohydrates and trans-fatty acids (mostly related to the widespread use of Vanaspati, a hydrogenated oil). Some data suggest that these nutrient imbalances are associated with insulin resistance, dyslipidaemia and subclinical inflammation in South Asians. Specifically, in children and young individuals, a high intake of n-6 PUFA is correlated with fasting hyperinsulinaemia, and in adults, high-carbohydrate meal consumption was reported to cause hyperinsulinaemia, postprandial hyperglycaemia and hypertriacylglycerolaemia. Dietary supplementation with n-3 PUFA leads to an improved lipid profile but not insulin sensitivity. Inadequate maternal nutrition in pregnancy, low birth weight and childhood 'catch-up' obesity may be important for the development of the metabolic syndrome and diabetes. Even in rural populations, who usually consume traditional frugal diets, there is an increasing prevalence of cardiovascular risk factors and the metabolic syndrome due to changes in diets and lifestyle. Nationwide community intervention programmes aimed at creating awareness about the consequences of unhealthy food choices and replacing them by healthy food choices are urgently needed in urban and rural populations in India, other countries in South Asia and in migrant South Asians. PMID:18842159

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

    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

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

    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.

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

    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...

  17. Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes.

    Manowsky, Julia; Camargo, Rodolfo Gonzalez; Kipp, Anna P; Henkel, Janin; Püschel, Gerhard P

    2016-06-01

    Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the β-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1β, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1β was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-κB. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKKβ, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues. PMID:27094035

  18. Methodological and Clinical Studies on Insulin Resistance in Childhood

    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...

  19. Successful Treatment of Type B Insulin Resistance With Rituximab

    Manikas, Emmanouil-Dimitrios; Isaac, Iona; Semple, Robert K.; Malek, Rana; Führer, Dagmar; Moeller, Lars C.

    2015-01-01

    Context: Type B insulin resistance is a very rare disease caused by autoantibodies against the insulin receptor. The mortality of type B insulin resistance is high (>50%), and management of this disease is not yet standardized. We report the successful treatment of a patient with type B insulin resistance with rituximab, cyclophosphamide, and prednisone. Case Description: A 45-year-old woman presented with unintended weight loss of 20 kg, unusually widespread acanthosis nigricans, and glucose...

  20. Preliminary evidence for obesity-associated insulin resistance in adolescents without elevations of inflammatory cytokines

    Cohen Jessica I

    2012-06-01

    Full Text Available Abstract Background To ascertain whether the associations between obesity, inflammation, and insulin resistance established in human adult studies are found among adolescents. Methods We contrasted 36 obese and 24 lean youth on fasting glucose, insulin levels, lipid profile, hemoglobin A1C, markers of hepatic function, white blood cell count, C-reactive protein (CRP and fibrinogen levels. The cytokines IL-6, TNF-α, IFN-γ, IL-10 and IL-4 and the adipokines leptin, resistin, and adiponectin were also compared between the two groups. The fasting glucose and insulin values were used to estimate the degree of insulin resistance with the homeostatic model assessment of insulin resistance (HOMA-IR. T-tests and correlations were run to examine group differences and associations between groups. In addition, regression analyses were used to ascertain whether the markers of inflammation were predictive of the degree of insulin resistance. Results Although obese adolescents had clear evidence of insulin resistance, only CRP, fibrinogen and leptin were elevated; there were no group differences in pro- or anti-inflammatory cytokines nor adiponectin and resistin. Anthropometric measures of obesity and level of insulin resistance were highly correlated to the acute phase reactants CRP and fibrinogen; however, the degree of insulin resistance was not predicted by the pro- or anti-inflammatory cytokine markers. Obese adolescents had higher white blood cell counts. In addition they had higher circulating alanine aminotransferase concentrations and lower circulating albumin and total protein than lean adolescents, possibly as a result of hepatocyte damage from fatty liver. Conclusion Unlike rodent or adult studies, we found that wide-spread systemic inflammation is not necessarily associated with insulin resistance among adolescents. This finding does not support the current paradigm that the associations between obesity and insulin resistance are, to a

  1. 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?

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

    2008-01-01

    -resistant subjects with the Flow-Mediated-Dilation (FMD) technique. We randomized subjects to intervention/control group, and examined the acute and chronic effect of nateglinide, an oral antidiabetic drug of rapid action. In the intervention group, postoral glucose-load (post-OGL) FMD delta values deteriorated when......-day "Closing day", p=0.001]. Post-OGL changes in the control group were nonsignificant both at Baseline and on Closing day. After a single dose of nateglinide "Acute day", post-OGL FMD deterioration was abolished. There was an increment in post-OGL FMD delta values most significant at 2 h post-OGL (p=0....... We found no relationship between postprandial hyperglycemia and post-OGL FMD....

  2. Vascular Stiffness in Insulin Resistance and Obesity

    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. Obesity, Insulin Resistance and Cancer Risk

    Jee, Sun Ha; Kim, Hee Jin; Lee, Jakyoung

    2005-01-01

    Obesity is a known cause of metabolic syndrome which includes Type II diabetes, hypertension, and dyslipidemia. It is well documented that insulin resistance contributes to the mortality and the incidence of metabolic syndromes including central obesity, dyslipidemia, hyperglycemia and hypertension. Both obesity and diabetes are emerging topics for researchers to consider as having a possible causal association with cancer since the two factors have been viewed as risk factors for cancer. The...

  4. Mitochondrial Deficiency Is Associated With Insulin Resistance

    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...

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

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

    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...

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

    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

  8. Fructose, insulin resistance, and metabolic dyslipidemia

    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. Effects of sleeve gastrectomy on insulin resistance

    CĂTOI, ADRIANA FLORINELA; PÂRVU, ALINA; MIRONIUC, AUREL; GALEA, ROMEO FLORIN; MUREŞAN, ADRIANA; BIDIAN, CRISTINA; POP, IOANA

    2016-01-01

    Background and aim Obesity is a major risk factor for the onset of insulin resistance (IR), hyperinsulinemia and type 2 diabetes mellitus (T2DM) Evidence data has proven that beyond important weight loss bariatric surgery especially Roux-en-Y gastric bypass (RYGB) and bilio-pancreatic diversion (BPD) leads to significant early reduction of insulinemia and of IR calculated through the homeostatic model assessment (HOMA-IR), independently of fat mass decrease. Sleeve gastrectomy (SG) is now used as a sole weight loss operation with good results. Therefore, the aim of the present study was to investigate the early changes of fasting blood glucose, insulin and HOMA-IR in a group of morbidly obese (MO) patients i.e. at 7, 30 and 90 days after SG. Methods The study included 20 MO patients (7 male and 13 female) submitted to SG. Anthropometrical (weight, body mass index –BMI, percent excess BMI loss -%EBMIL) and biochemical (plasma glucose, insulin and calculated HOMA-IR ) evaluation were performed before and at 7, 30 and 90 days after SG. In addition, a second group of 10 normal weight healthy subjects with a BMI ranging form 19 kg/m2 to 23.14 kg/m2, matched for age and gender was investigated. Results Plasma glucose (p=0.018), insulin (p=0.004) and HOMA-IR (p=0.006) values were statistically different between the studied groups. After surgery, at every follow-up point, there were statistically different weight and BMI mean values relative to the operation day (p<0.003). BMI, decreased at 7 days (estimated reduction=2.79; 95% CI:[2.12;3.45]), at 30 days (estimated reduction=5.65; 95% CI:[3.57;7.73]) and at 90 days (estimated reduction=10.88; 95% CI:[7.35;14.41]) respectively after SG. We noted a tendency toward statistical significant change of mean insulin values at 7 days after surgery (corrected p=0.075), no statistical change at 30 days (corrected p=0.327) and a significant change at 90 days (corrected p=0.027) after SG as compared to baseline. There was a

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

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

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

    2012-01-01

    tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. WHAT THIS STUDY ADDS: This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses of...... ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIM The introduction of...... of NODAT remains unclear. We sought to compare the impact of CsA and Tac on glucose metabolism in human subjects. METHODS: Ten healthy men underwent 5 h infusions of CsA, Tac and saline in a randomized, double-blind, crossover study. During infusion glucose metabolism was investigated using following...

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

    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.

  13. Metabolic syndrome and insulin resistance in obese adolescents

    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.

  14. Cerebral blood flow links insulin resistance and baroreflex sensitivity.

    John P Ryan

    Full Text Available Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p < .05. Moreover, the relationship between insulin resistance and baroreflex sensitivity was statistically mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01. Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes.

  15. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men

    Alibegovic, A C; Sonne, M P; Højbjerre, L;

    2010-01-01

    of insulin resistance, bed rest resulted in a paradoxically increased response to acute insulin stimulation in the general expression of genes, particularly those involved in inflammation and endoplasmatic reticulum (ER) stress. Furthermore, bed rest changed gene expressions of several insulin...... resistance and diabetes candidate genes. We also observed a trend toward increased PPARGC1A DNA methylation after bed rest. We conclude that impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in...

  16. Cerebral Blood Flow Links Insulin Resistance and Baroreflex Sensitivity

    Ryan, John P.; Sheu, Lei K.; Verstynen, Timothy D.; Onyewuenyi, Ikechukwu C.; Gianaros, Peter J.

    2013-01-01

    Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regula...

  17. Method for preventing and/or treating insulin resistance

    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

  18. Severe Insulin Resistance Improves Immediately After Sleeve Gastrectomy.

    Sharma, Rahul; Hassan, Chandra; Chaiban, Joumana T

    2016-01-01

    Introduction. Obese individuals exhibit insulin resistance often leading to adverse health outcomes. When compared with intensive medical therapy, bariatric surgery has shown better outcomes mainly in terms of insulin resistance and glycemic control. Using the Homeostasis Model Assessment of insulin resistance (HOMA-IR), we report herein a case illustrating a drastic improvement in severe insulin resistance after sleeve gastrectomy in the immediate postoperative period. Case Report. A patient with long-standing history of morbid obesity, type 2 diabetes, obstructive sleep apnea, hypertension, and severe insulin resistance (requiring approximately 2 units of insulin per kg per day) was enrolled in the medical weight management program for 6 months during which he lost 40 lbs and his insulin requirements decreased. He then underwent a sleeve gastrectomy and did not require insulin therapy as of postoperative day 1. His HOMA-IR improved by about 76% between day 1 and day 14 postoperatively. Conclusion. Sleeve gastrectomy leads to a drastic improvement in severe insulin resistance as early as the first postoperative day. PMID:26788532

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

    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...

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

    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

  1. Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus

    The mechanisms of the diminished hypoglycemic response to insulin in non-insulin-dependent diabetes mellitus (NIDDM) with normal levels of circulating plasma insulin were investigated. Specific binding of mono-125I (Tyr A14)-insulin to isolated adipocytes and effects of insulin (5--10,000 microunits/ml) on glucose oxidation and lipolysis were determined simultaneously in subcutaneous adipose tissue of seven healthy subjects of normal weight and seven untreated NIDDM patients with normal plasma insulin levels. The two groups were matched for age, sex, and body weight. Insulin binding, measured in terms of receptor number and affinity, was normal in NIDDM, the total number of receptors averaging 350,000 per cell. Neither sensitivity nor the maximum antilipolytic effect of insulin was altered in NIDDM patients as compared with control subjects; the insulin concentration producing half the maximum effect (ED50) was 10 microunits/ml. As regards the effect of insulin on glucose oxidation, for the control subjects ED50 was 30 microunits/ml, whereas in NIDDM patients, insulin exerted no stimulatory effect. The results obtained suggest that the effect of insulin on glucose utilization in normoinsulinemic NIDDM may be diminished in spite of normal insulin binding to receptors. The resistance may be due solely to postreceptor defects, and does not involve antilipolysis

  2. Insulin resistance in human subjects having impaired glucose regulation

    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)

  3. Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance.

    Saad, M J A; Santos, A; Prada, P O

    2016-07-01

    Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities. PMID:27252163

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

    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.

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

    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.

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

    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)

  7. In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R;

    2005-01-01

    In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... > .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....... insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant...

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

    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...

  9. Insulin resistance and breast-cancer risk.

    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

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

    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

  11. Prevalence of insulin resistance in obese adolescents

    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

  12. Prevalence of insulin resistance in obese adolescents

    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

  13. Cerebral blood flow links insulin resistance and baroreflex sensitivity.

    Ryan, John P; Sheu, Lei K; Verstynen, Timothy D; Onyewuenyi, Ikechukwu C; Gianaros, Peter J

    2013-01-01

    Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old) who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01). Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes. PMID:24358272

  14. Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

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

    2010-01-01

    BACKGROUND: The incidence of the insulin resistance syndrome has increased at an alarming rate worldwide creating a serious challenge to public health care in the 21st century. Recently, epidemiological studies have associated the prevalence of type 2 diabetes with elevated body burdens...... 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...... 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...

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

    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.

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

    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...

  17. Lipocalin-2 inhibits autophagy and induces insulin resistance in H9c2 cells.

    Chan, Yee Kwan; Sung, Hye Kyoung; Jahng, James Won Suk; Kim, Grace Ha Eun; Han, Meng; Sweeney, Gary

    2016-07-15

    Lipocalin-2 (Lcn2; also known as neutrophil gelatinase associated lipocalin, NGAL) levels are increased in obesity and diabetes and associate with insulin resistance. Correlations exist between Lcn2 levels and various forms or stages of heart failure. Insulin resistance and autophagy both play well-established roles in cardiomyopathy. However, little is known about the impact of Lcn2 on insulin signaling in cardiomyocytes. In this study, we treated H9c2 cells with recombinant Lcn2 for 1 h followed by dose- and time-dependent insulin treatment and found that Lcn2 attenuated insulin signaling assessed via phosphorylation of Akt and p70S6K. We used multiple assays to demonstrate that Lcn2 reduced autophagic flux. First, Lcn2 reduced pULK1 S555, increased pULK1 S757 and reduced LC3-II levels determined by Western blotting. We validated the use of DQ-BSA to assess autolysosomal protein degradation and this together with MagicRed cathepsin B assay indicated that Lcn2 reduced lysosomal degradative activity. Furthermore, we generated H9c2 cells stably expressing tandem fluorescent RFP/GFP-LC3 and this approach verified that Lcn2 decreased autophagic flux. We also created an autophagy-deficient H9c2 cell model by overexpressing a dominant-negative Atg5 mutant and found that reduced autophagy levels also induced insulin resistance. Adding rapamycin after Lcn2 could stimulate autophagy and recover insulin sensitivity. In conclusion, our study indicated that acute Lcn2 treatment caused insulin resistance and use of gain and loss of function approaches elucidated a causative link between autophagy inhibition and regulation of insulin sensitivity by Lcn2. PMID:27090568

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

    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...

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

    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

  20. The Association Between IGF-I and Insulin Resistance

    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...

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

    "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.

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

    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...

  3. [Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene].

    Ros, P; Colino-Alcol, E; Grasso, V; Barbetti, F; Argente, J

    2015-01-01

    Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory. PMID:25027621

  4. Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke.

    Lioutas, Vasileios-Arsenios; Alfaro-Martinez, Freddy; Bedoya, Francisco; Chung, Chen-Chih; Pimentel, Daniela A; Novak, Vera

    2015-08-01

    Treatment options for stroke remain limited. Neuroprotective therapies, in particular, have invariably failed to yield the expected benefit in stroke patients, despite robust theoretical and mechanistic background and promising animal data. Insulin and insulin-like growth factor 1 (IGF-1) play a pivotal role in critical brain functions, such as energy homeostasis, neuronal growth, and differentiation. They may exhibit neuroprotective properties in acute ischemic stroke based upon their vasodilatory, anti-inflammatory and antithrombotic effects, as well as improvements of functional connectivity, neuronal metabolism, neurotransmitter regulation, and remyelination. Intranasally administered insulin has demonstrated a benefit for prevention of cognitive decline in older people, and IGF-1 has shown potential benefit to improve functional outcomes in animal models of acute ischemic stroke. The intranasal route presents a feasible, tolerable, safe, and particularly effective administration route, bypassing the blood-brain barrier and maximizing distribution to the central nervous system (CNS), without the disadvantages of systemic side effects and first-pass metabolism. This review summarizes the neuroprotective potential of intranasally administered insulin and IGF-1 in stroke patients. We present the theoretical background and pathophysiologic mechanisms, animal and human studies of intranasal insulin and IGF-1, and the safety and feasibility of intranasal route for medication administration to the CNS. PMID:26040423

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

    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.

  6. Insulin resistance and mitochondrial function in skeletal muscle

    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...

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

    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.

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

    Højlund, Kurt

    2014-01-01

    Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity....... 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...... action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients...

  9. Xylitol prevents NEFA-induced insulin resistance in rats

    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

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

    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.

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

    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.

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

    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 ...

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

    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

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

    Gurav, Abhijit N.

    2012-01-01

    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, ...

  15. Insulin resistance and exercise tolerance in heart failure patients

    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....

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

    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.

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

    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

  18. INFLUENCE OF ACUPUNCTURE ON INSULIN RESISTANCE IN OBESITY PATIENTS

    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.

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

    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.

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

    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.

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

    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...

  2. Interleukin-6 and insulin resistance in obese adolescents

    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.].

  3. Insulin resistance: The linchpin between prediabetes and cardiovascular disease.

    Salazar, Martin R; Carbajal, Horacio A; Espeche, Walter G; Aizpurúa, Marcelo; Leiva Sisnieguez, Carlos E; Leiva Sisnieguez, Betty C; Stavile, Rodolfo N; March, Carlos E; Reaven, Gerald M

    2016-03-01

    The aim of this study was to test the hypothesis that cardiovascular disease occurs to the greatest extent in persons with prediabetes mellitus who are also insulin resistant. In 2003, 664 non-diabetic women (n = 457) and men (n = 207), aged 52 ± 16 and 53 ± 15 years, were surveyed during a programme for cardiovascular disease prevention. Fasting plasma glucose concentrations defined participants as having normal fasting plasma glucose (fasting plasma glucose <5.6 mmol/L) or prediabetes mellitus (fasting plasma glucose ⩾5.6 and <7.0 mmol/L). The tertile of prediabetes mellitus subjects with the highest fasting plasma insulin concentration was classified as insulin resistant. Baseline cardiovascular disease risk factors were accentuated in prediabetes mellitus versus normal fasting glucose, particularly in prediabetes mellitus/insulin resistant. In 2012, 86% of the sample were surveyed again, and the crude incidence for cardiovascular disease was higher in subjects with prediabetes mellitus versus normal fasting glucose (13.7 vs 6.0/100 persons/10 years; age- and sex-adjusted hazard ratio = 1.88, p = 0.052). In prediabetes mellitus, the crude incidences were 22.9 versus 9.6/100 persons/10 years in insulin resistant versus non-insulin resistant persons (age- and sex-adjusted hazard ratio = 2.36, p = 0.040). In conclusion, cardiovascular disease risk was accentuated in prediabetes mellitus/insulin resistant individuals, with a relative risk approximately twice as high compared to prediabetes mellitus/non-insulin resistant subjects. PMID:26802220

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

    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

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

    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

  6. Obesity, Insulin Resistance and Pregnancy Outcome

    Catalano, Patrick M.

    2010-01-01

    There has been a significant increase over the past few decades in the number of reproductive age women who are either overweight or obese. Overweight and obese women are at increased risk for having decreased insulin sensitivity as compared with lean or average weight women. The combination of obesity and decreased insulin sensitivity increases the long term risk of these individuals developing the metabolic syndrome and associated problems of diabetes, hypertension, hyperlipidemia and cardi...

  7. Association of insulin resistance with obesity in children

    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)

  8. Adipose Tissue Hypoxia, Inflammation, and Fibrosis in Obese Insulin-Sensitive and Obese Insulin-Resistant Subjects.

    Lawler, Helen M; Underkofler, Chantal M; Kern, Philip A; Erickson, Christopher; Bredbeck, Brooke; Rasouli, Neda

    2016-04-01

    We confirmed fat hypoxia in obese as compared to lean subjects. However, fat oxygenation was similar in obese insulin sensitive and insulin resistant subjects suggesting fat hypoxia may be simply a consequence of fat expansion. PMID:26871994

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

    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...

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

    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...

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

    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

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

    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...

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

    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...

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

    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-...

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

    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...

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

    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...

  17. Insulin resistance in skeletal muscles of caveolin-3-null mice

    Oshikawa, Jin; Otsu, Koji; Toya, Yoshiyuki; Tsunematsu, Takashi; Hankins, Raleigh; Kawabe, Jun-ichi; Minamisawa, Susumu; Umemura, Satoshi; Hagiwara, Yasuko; Ishikawa, Yoshihiro

    2004-01-01

    Type 2 diabetes is preceded by the development of insulin resistance, in which the action of insulin is impaired, largely in skeletal muscles. Caveolin-3 (Cav3) is a muscle-specific subtype of caveolin, an example of a scaffolding protein found within membranes. Cav is also known as growth signal inhibitor, although it was recently demonstrated that the genetic disruption of Cav3 did not augment growth in mice. We found, however, that the lack of Cav3 led to the development of insulin resista...

  18. ADVANCES OF STUDIES ON ACUPUNCTURE TREATMENT OF INSULIN RESISTANCE

    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.

  19. Insulin resistance as a physiological defense against metabolic stress

    Nolan, Christopher J; Ruderman, Neil B; Kahn, Steven E;

    2015-01-01

    challenging subgroup of patients with T2D who are overweight or obese with insulin resistance (IR) and the most refractory hyperglycemia due to an inability to change lifestyle to reverse positive energy balance. For this subgroup of patients with T2D, we question the dogma that IR is primarily harmful...... 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...

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

    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.

  1. Immunometabolism of AMPK in insulin resistance and atherosclerosis.

    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

  2. Visceral adiposity, insulin resistance and cancer risk

    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.

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

    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...

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

    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.

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

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

    2007-01-01

    -cholesterol, and lower high-density lipoprotein-cholesterol, and insulin response to higher heart rate, blood pressure and fasting glucose, and the same dyslipidemic profile as IR (P < or = 0.05 for all). By factor analysis, three main factors (related to IR, age, and fatness, respectively) appeared to underlie......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...

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

    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

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

    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.

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

    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...

  9. Studies of insulin resistance in congenital generalized lipodystrophy

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

    1996-01-01

    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......, immunoreactive protein and mRNA levels. The patients had fasting hyperinsulinaemia, and the rate of total glucose disposal was severely impaired, primarily due to a decreased non-oxidative glucose metabolism. In the patient studied with muscle biopsy, the expected activation of glycogen synthase by insulin did...... not occur. In both patients there was severely increased hepatic glucose output in the basal state, suggesting a failure of insulin to suppress hepatic gluconeogenesis. During insulin infusion a substantially elevated rate of lipid oxidation remained in the patients, in contrast to the almost completely...

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

    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

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

    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.

  12. Role of PTEN in TNFα induced insulin resistance

    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.

  13. Role of PTEN in TNFα induced insulin resistance

    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

  14. Relationship of serum resistin with insulin resistance and obesity

    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)

  15. Acute suppression of apo B secretion by insulin occurs independently of MTP

    Sparks, Janet D.; Chamberlain, Jeffrey; O’Dell, Colleen; Khatun, Irani; Hussain, M. Mahmood; Sparks, Charles E.

    2011-01-01

    Secretion of apolipoprotein (apo) B-containing lipoproteins by the liver depends mainly upon apo B availability and microsomal triglyceride transfer protein (MTP) activity and is subject to insulin regulation. Hepatic MTP mRNA expression is negatively regulated by insulin which correlates with inhibition of apo B secretion suggesting that insulin might suppress apo B secretion through an MTP-dependent mechanism. To investigate this possibility, we examined the acute effect of insulin on hepat...

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

    Groeneveld, Matthijs P.; Brierley, Gemma V.; Rocha, Nuno M.; Siddle, Kenneth; 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 lentiviral system to knock down Insr or its substrates Irs1 and Irs2 conditionally in 3T3-L1 murine preadipocytes/adipocytes to assess whether acute loss of their expression has different consequences to withdrawal of insulin. Efficient knockdown of either Insr or Irs1/2 was achieved by conditional shRNA expression, severely attenuating insulin-stimulated AKT phosphorylation and glucose uptake. Dual knockdown of Irs1 and Irs2 but not Insr in preadipocytes impaired differentiation to adipocytes. Acute knockdown of Insr or both Irs1 and Irs2 in adipocytes increased Adipoq mRNA expression but reduced adiponectin secretion, assessed by immunoassay. Knockdown sustained for 14 days also reduced immunoassay-detected adiponectin secretion, and moreover induced delipidation of the cells. These findings argue against a distinct effect of Insr deficiency to promote adiponectin secretion as the explanation for paradoxical insulin receptoropathy-related hyperadiponectinaemia. PMID:26888756

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

    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

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

    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

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

    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...

  20. Effects of Diet and Exercise on Insulin Resistance during Pregnancy.

    Clapp, James F

    2006-01-01

    Current evidence suggests that both diet and exercise can alter the usual increase in insulin resistance seen in Western societies during mid and late pregnancy. A low-glycemic diet combined with a low-volume exercise regimen during pregnancy decreases the glucose and insulin response to both mixed caloric intake and exercise, and probably lowers both 24-h blood glucose concentrations and the maternal substrate utilization ratio of carbohydrate/fat. The end result is a marked decrease in both maternal weight gain and size at birth. Regular weight-bearing exercise alone lowers markers of insulin resistance and lowers blood glucose concentration during and immediately after exercise during pregnancy. Changes in diet and/or physical activity appear to prevent the onset of gestational diabetes mellitus in at-risk women and may be of value in the treatment of those who develop gestational diabetes. PMID:18370754

  1. Postexercise muscle glycogen resynthesis in obese insulin-resistant Zucker rats.

    Bruce, C R; Lee, J S; Hawley, J A

    2001-10-01

    We determined the effect of an acute bout of swimming (8 x 30 min) followed by either carbohydrate administration (0.5 mg/g glucose ip and ad libitum access to chow; CHO) or fasting (Fast) on postexercise glycogen resynthesis in soleus muscle and liver from female lean (ZL) and obese insulin-resistant (ZO) Zucker rats. Resting soleus muscle glycogen concentration ([glycogen]) was similar between genotypes and was reduced by 73 (ZL) and 63% (ZO) after exercise (P supercompensation in both genotypes (68% vs. 44% for ZL and ZO). With CHO, liver [glycogen] was restored to resting levels in ZL but remained at postexercise values for ZO after both treatments. We conclude that the increased glucose availability with carbohydrate refeeding after glycogen-depleting exercise resulted in glycogen supercompensation, even in the face of muscle insulin-resistance. PMID:11568131

  2. Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects

    Soronen Jarkko

    2012-04-01

    Full Text Available Abstract Background To get insight into molecular mechanisms underlying insulin resistance, we compared acute in vivo effects of insulin on adipose tissue transcriptional profiles between obese insulin-resistant and lean insulin-sensitive women. Methods Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 hours of intravenously maintained euglycemic hyperinsulinemia from 9 insulin-resistant and 11 insulin-sensitive females. Gene expression was measured using Affymetrix HG U133 Plus 2 microarrays and qRT-PCR. Microarray data and pathway analyses were performed with Chipster v1.4.2 and by using in-house developed nonparametric pathway analysis software. Results The most prominent difference in gene expression of the insulin-resistant group during hyperinsulinemia was reduced transcription of nuclear genes involved in mitochondrial respiration (mitochondrial respiratory chain, GO:0001934. Inflammatory pathways with complement components (inflammatory response, GO:0006954 and cytokines (chemotaxis, GO:0042330 were strongly up-regulated in insulin-resistant as compared to insulin-sensitive subjects both before and during hyperinsulinemia. Furthermore, differences were observed in genes contributing to fatty acid, cholesterol and triglyceride metabolism (FATP2, ELOVL6, PNPLA3, SREBF1 and in genes involved in regulating lipolysis (ANGPTL4 between the insulin-resistant and -sensitive subjects especially during hyperinsulinemia. Conclusions The major finding of this study was lower expression of mitochondrial respiratory pathway and defective induction of lipid metabolism pathways by insulin in insulin-resistant subjects. Moreover, the study reveals several novel genes whose aberrant regulation is associated with the obese insulin-resistant phenotype.

  3. Waist circumference and insulin resistance: a cross-sectional study of Japanese men

    Hamachi Tadamichi; Yoshimitsu Shinichiro; Tabata Shinji; Abe Hiroshi; Ohnaka Keizo; Kono Suminori

    2009-01-01

    Abstract Background Visceral obesity is positively related to insulin resistance. The nature of the relationship between waist circumference and insulin resistance has not been known in Japanese populations. This study examined the relationship between waist circumference and insulin resistance and evaluated the optimal cutoff point for waist circumference in relation to insulin resistance in middle-aged Japanese men. Methods Study subjects included 4800 Japanese men aged 39 to 60 years. Insu...

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

    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

  5. Immunity as a link between obesity and insulin resistance

    Type-2 diabetes mellitus (T2DM) is a major health problem in the United States and worldwide. Obesity is causally linked to the pathogenesis of insulin resistance, metabolic syndrome and T2DM. A chronic low-grade inflammation occurring in adipose tissue is at least in part responsible for the obesit...

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

    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

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

    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.

  8. Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure

    Bjerre, M.; Kistorp, C.; Hansen, T.K.;

    2010-01-01

    CRP), endothelial activation (soluble E-selectin, sEsel)), endothelial damage/dysfunction (von Willebrand factor, vWf) and insulin resistance (IR) and prognosis in CHF remains unknown. Design. We investigated the association(s) between plasma sMAC, hsCRP, sEsel, vWf and IR (assessed by homeostatic model assessment...

  9. Skeletal muscle lipid metabolism in exercise and insulin resistance

    Kiens, Bente

    2006-01-01

    Lipids as fuel for energy provision originate from different sources: albumin-bound long-chain fatty acids (LCFA) in the blood plasma, circulating very-low-density lipoproteins-triacylglycerols (VLDL-TG), fatty acids from triacylglycerol located in the muscle cell (IMTG), and possibly fatty acids...... of insulin resistance in skeletal muscle, including possible molecular mechanisms involved, is discussed....

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

    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...

  11. Insulin resistance in sub clinical hypothyroidism

    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

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

    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.

  13. Accuracy and optimization of a subcutaneous insulin model for less acute critical care patients.

    Thomas, Felicity; Dickson, Jennifer; Pretty, Chris; Stewart, Kent; Fisk, Liam; Shaw, Geoffrey; Chase, J Geoffrey

    2015-08-01

    Extending safe, effective glycemic control to the general wards requires a simple approach using subcutaneous (SC) insulin. However, this approach can increase relative risk compared to intravenous insulin due to the increased variability of SC insulin appearance. This paper evaluates the accuracy of a SC plasma insulin model and optimizes its parameters using measured plasma insulin data from 6 less acute critical care patients treated with SC insulin. The SC plasma insulin model used captures the dynamics of regular SC insulin well. However, there appears to be a positive bias leading to an overall median [IQR] residual error of -28.3 [-37 - 19] mU/L. The optimized model reduced the RMS residual error by 20-70% for each patient. The distinct inter- and intra-patient, and cohort variation seen in this data highlights the importance to of understanding how SC insulin appearance dynamics may be affected by the subject condition. PMID:26737279

  14. Monomeric Tartrate Resistant Acid Phosphatase Induces Insulin Sensitive Obesity

    Lång, Pernilla; van Harmelen, Vanessa; Rydén, Mikael; Kaaman, Maria; Parini, Paolo; Carneheim, Claes; Cassady, A. Ian; Hume, David A.; Andersson, Göran; Arner, Peter

    2008-01-01

    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...

  15. Association of Nocturnal Melatonin Secretion With Insulin Resistance in Nondiabetic Young Women

    McMullan, Ciaran J.; CURHAN, Gary C.; Schernhammer, Eva S.; Forman, John P.

    2013-01-01

    Exogenous melatonin ameliorates insulin resistance in animals, while among humans, polymorphisms in the melatonin receptor gene are associated with insulin resistance. We aimed to investigate the association of endogenous nocturnal melatonin secretion with insulin resistance in humans. We analyzed the association between endogenous nocturnal melatonin secretion, estimated by measuring the main melatonin metabolite, 6-sulfatoxymelatonin, from the first morning urinary void, and the prevalence ...

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

    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

  17. Anaesthesia generates neuronal insulin resistance by inducing hypothermia

    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.

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

    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

  19. Is myopia another clinical manifestation of insulin resistance?

    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

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

    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...

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

    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

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

    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.

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

    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

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

    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...

  5. Development of Wistar rat model of insulin resistance

    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.

  6. Proinsulin and insulin profile in acute myocardial infarction

    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)

  7. Proinsulin and insulin profile in acute myocardial infarction

    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.

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

    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...... fasting RQ) were also assessed. Glucose incremental area under the curve was calculated from the OGTT (iAUCOGTT). Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than IFG+IGT (P...... in adults with IFG, IGT or IFG+IGT is unknown. Twenty-four older (66.7±0.8yr) obese (34.2±0.9kg/m(2)) adults were categorized as IFG (n=8), IGT (n=8), or IFG+IGT (n=8) according to a 75-gram oral glucose tolerance test (OGTT). Subjects underwent 12-weeks of exercise (60 min/d for 5 d/wk at ~85% HRmax...

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

    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

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

    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.

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

    To evaluate the effects of turtle oil on insulin sensitivity and glucose metabolism in an insulin-resistant (IR) cell model which was established by the way of high concentration of insulin induction with HepG2 cell in vitro culture. The IR cells were treated by turtle oil, the glucose consumption and 3H-D-glucose incorporation rate in IR cells were detected by the way of glucose oxidase and 3H-D-glucose incorporation assay respectively. The state of cell proliferation was tested by MTT method. The results showed that the incorporation rate of 3H-D-glucose in IR cells was significantly lower than that in the control cells(P3H-D-glucose incorporation rate in either IR cells or control cells was increased with the increase of insulin concentration. Moreover, the 3H-D-glucose incorporation rate of IR cells increased slower than that of control cells. The MTT assay showed that turtle oil can promote the proliferation of IR cell and control cell. The glucose uptake and glucose consumption in IR cell which treated with turtle oil was significantly increase than that in the control cells (P<0.05). Turtle oil can improve the insulin sensitivity and glucose metabolism in the IR cell model. (authors)

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

    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...

  13. The Role of Hepatic FoxO1 in Insulin Resistance

    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...

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

    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...

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

    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)

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

    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....

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

    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....

  18. Metabolic programming in the pathogenesis of insulin resistance.

    Devaskar, Sherin U; Thamotharan, Manikkavasagar

    2007-06-01

    This review focuses on different animal models of nutrient perturbations, inclusive of restrictive and excessive states mimicking human situations during pregnancy and lactation that cause aberrations in the offspring. These aberrations consist of diminished insulin sensitivity in the presence of defective insulin production. These phenotypic changes are due to altered peripheral tissue post-insulin receptor signaling mechanisms and pancreatic beta-islet insulin synthesis and secretion defects. While these changes during in utero or postnatal life serve as essential adaptations to overcome adverse conditions, they become maladaptive subsequently and set the stage for type 2 diabetes mellitus. Pregnancy leads to gestational diabetes with trans-generational propagation of the insulin resistant phenotype. This is in response to the metabolically aberrant maternal in utero environment, and tissue specific epigenetic perturbations that permanently alter expression of critical genes transmitted to future generations. These heritable aberrations consisting of altered DNA methylation and histone modifications remodel chromatin and affect transcription of key genes. Along with an altered in utero environment, these chromatin modifications contribute to the world-wide epidemic of type 2 diabetes mellitus, with nutrient excess dominating in developed and nutrient restriction in developing countries. PMID:17657604

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

    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/ETAR during insulin resistance, ETAR 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, ETAR expression, but not ETBR, 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 ETAR pathway suppressed insulin-induced AKT

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

    Vestergaard, H; Lund, S; Pedersen, O; Vestergaard, Henrik

    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....

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

    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 are...... associated with an age-related decrease in the physical activity level and can be counteracted by increased physical activity of a resistive nature. Strength training has been shown to improve insulin-stimulated glucose uptake in both healthy elderly individuals and patients with manifest diabetes, and...... likewise to improve muscle strength in both elderly healthy individuals and in elderly individuals with chronic disease. The increased strength is coupled to improved function and a decreased risk for fall injuries and fractures. Elderly individuals have preserved the capacity to improve muscle strength...

  2. The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis.

    Choi, Kyung Mook

    2016-03-01

    Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines) may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis. PMID:26996418

  3. Insulin

    ... 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 ...

  4. Hyperandrogenism-Insulin Resistance-Acanthosis Nigricans Syndrome

    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...

  5. Insulin resistance of muscle protein metabolism in aging

    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...

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

    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

  7. Sildenafil Reduces Insulin-Resistance in Human Endothelial Cells

    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...

  8. Lifecourse Childhood Adiposity Trajectories Associated With Adolescent Insulin Resistance

    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 ...

  9. [Free fatty acids: mediators of insulin resistance and atherosclerosis].

    Castro Cabezas, M; Erkelens, D W; van Dijk, H

    2002-01-19

    Free fatty acids (FFAs) are involved in the transportation of energy; in the postprandial phase to the peripheral tissues and in the postabsorptive phase from the adipose tissue to the liver. In the postprandial phase, FFAs are mainly derived from hydrolysis of triglyceride-rich particles like chylomicrons and very low-density lipoproteins (VLDL). The flux of FFAs is directed to peripheral cells such as adipocytes and muscle cells. In the postabsorptive period, FFAs are transported to the liver after being released from intracellular storage in the adipocytes. Complement component 3 (C3) plays an important role in the uptake of free fatty acids by the peripheral cells and their esterification to triglycerides. Since C3 is also involved in the pathogenesis of the insulin resistance syndrome, and since a deviant FFA metabolism with an increased FFA flux to the liver may induce insulin resistance, it is hypothesized that C3 may form the missing link between FFA metabolism and insulin resistance. In addition, recent studies have increasingly indicated that atherosclerosis is in fact an inflammation-based process involving complement-dependent responses, in which FFAs seem to play a role in the complement-dependent pathway. It has recently become apparent that FFAs have a regulatory function in the transcription of DNA, in relation to lipoprotein metabolism. This is where PPAR-gamma and PPAR-alpha agonists ('glitazones' and fibrates respectively) are active (PPAR is an abbreviation for peroxisome proliferation activating receptor). Glitazons may play an important role in the treatment of insulin resistance and related disorders. Acquiring more knowledge about the relationship between complement and FFA metabolism may increase our understanding of these processes and provide openings for the development of new antiatherogenic strategies. PMID:11826668

  10. The Links Between Insulin Resistance, Diabetes, and Cancer

    Orgel, Etan; Mittelman, Steven D

    2013-01-01

    The growing epidemic of obesity has resulted in a large increase in multiple related diseases. Recent evidence has strengthened the proposed synergistic relationship between obesity-related insulin resistance (IR) and/or diabetes mellitus (DM) and cancer. Within the past year, many studies have examined this relationship. Although the precise mechanisms and pathways are uncertain, it is becoming clear that hyperinsulinemia and possibly sustained hyperglycemia are important regulators of not o...

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

    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

    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....... Interestingly, dozens 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...

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

    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

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

    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...

  15. Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women

    Iskra Bitoska

    2016-02-01

    CONCLUSION: HRT was associated with statistically signifficant increase of insulin sensitivity. Larger clinical trials will be necessary to understand whether HRT may improve insulin resistance and glucose homeostasis in women with diabetes, especially when given shortly after entering menopause.

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

    Mimi Z Chen

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

  17. Sphingolipids: the nexus between Gaucher disease and insulin resistance

    Fuller Maria

    2010-10-01

    Full Text Available Abstract Sphingolipids constitute a diverse array of lipids in which fatty acids are linked through amide bonds to a long-chain base, and, structurally, they form the building blocks of eukaryotic membranes. Ceramide is the simplest and serves as a precursor for the synthesis of the three main types of complex sphingolipids; sphingomyelins, glycosphingolipids and gangliosides. Sphingolipids are no longer considered mere structural spectators, but bioactive molecules with functions beyond providing a mechanically stable and chemically resistant barrier to a diverse array of cellular processes. Although sphingolipids form a somewhat minor component of the total cellular lipid pool, their accumulation in certain cells forms the basis of many diseases. Human diseases caused by alterations in the metabolism of sphingolipids are conventionally inborn errors of degradation, the most common being Gaucher disease, in which the catabolism of glucosylceramide is defective and accumulates. Insulin resistance has been reported in patients with Gaucher disease and this article presents evidence that this is due to perturbations in the metabolism of sphingolipids. Ceramide and the more complex sphingolipids, the gangliosides, are constituents of specialised membrane microdomains termed lipid rafts. Lipid rafts play a role in facilitating and regulating lipid and protein interactions in cells, and their unique lipid composition enables them to carry out this role. The lipid composition of rafts is altered in cell models of Gaucher disease which may be responsible for impaired lipid and protein sorting observed in this disorder, and consequently pathology. Lipid rafts are also necessary for correct insulin signalling, and a perturbed lipid raft composition may impair insulin signalling. Unravelling common nodes of interaction between insulin resistance and Gaucher disease may lead to a better understanding of the biochemical mechanisms behind pathology.

  18. Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice

    Keung, Wendy; Ussher, John R.; Jaswal, Jagdip S.; Raubenheimer, Monique; Lam, Victoria H.M.; Wagg, Cory S.; Lopaschuk, Gary D

    2013-01-01

    Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to insulin resistance and glucose intolerance. However, increasing muscle fatty acid oxidation may cause a reciprocal decrease in glucose oxidation, which might impair insulin sensitivity and glucose tolerance. We therefore investigated what effect inhibition of mitochondrial fatty acid uptake has on whole-body glucose tolerance and insulin sensitivity in obese insulin-resistant mice. C57BL/6 mice were fed a high-f...

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

    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...

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

    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

  1. 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.

    Caro, J F; Ittoop, O; Pories, W J; Meelheim, D; Flickinger, E G; F. Thomas; 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...

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

    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

  3. Role of oxidative stress in endothelial insulin resistance

    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.

  4. 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

    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

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

    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

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

    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 ...

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

    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. PMID:25814291

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

    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...... and insulin resistance over an average of 12 years were performed in a subset of the Registry consisting of 338 (184 monozygotic and 154 dizygotic) same-sex twin pairs. RESULTS: Age at baseline examination was 37.4 ± 9.6 (mean ± SD) years. Baseline insulin resistance was not associated with age......-dependent changes in LTL (attrition) over the follow-up period, whereas baseline LTL was associated with changes in insulin resistance during this period. The shorter the LTL at baseline, the more pronounced was the increase in insulin resistance over the follow-up period (p 

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

    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

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

    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

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

    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.

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

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

    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...

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

    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...

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

    Rager, Kristin M.; Omar, Hatim A.

    2006-01-01

    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 nigrican...

  16. Insulin resistance, adiponectin and adverse outcomes following elective cardiac surgery: a prospective follow-up study

    Hjortdal Vibeke E; Christensen Thomas D; Andersen Niels H; Gjedsted Jakob; Hansen Troels K; Mikkelsen Martin M; Johnsen Søren P

    2010-01-01

    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 unde...

  17. DHEA administration and exercise training improves insulin resistance in obese rats

    Sato Koji

    2012-05-01

    Full Text Available Abstract Background Dehydroepiandrosterone (DHEA is precursor of sex steroid hormone. We demonstrated that acute DHEA injection to type 1 diabetes model rats induced improvement of hyperglycemia. However, the effect of the combination of DHEA administration and exercise training on insulin resistance is still unclear. This study was undertaken to determine whether 6-weeks of DHEA administration and/or exercise training improve insulin resistance in obese male rats. Methods After 14 weeks of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of four groups: control, DHEA administration, exercise training, and a combination of DHEA administration and exercise training (n = 10 each group. Results After 6-weeks of DHEA administration and/or exercise training, rats in the combination group weighed significantly less and had lower serum insulin levels than rats in the other groups. Moreover, the rats treated with DHEA alone or DHEA and exercise had significantly lower fasting glucose levels (combination, 84 ± 6.5 mg/dL; DHEA, 102 ± 9.5 mg/dL; control, 148 ± 10.5 mg/dL. In addition, insulin sensitivity check index showed significant improvements in the combination group (combination, 0.347 ± 0.11; exercise, 0.337 ± 0.16%; DHEA, 0.331 ± 0.14; control, 0.308 ± 0.12. Muscular DHEA and 5α-dihydrotestosterone (DHT concentrations were significantly higher in the combination group, and closely correlated with the quantitative insulin-sensitivity check index (DHEA: r = 0.71, p r = 0.69, p  Conclusion These results showed that a combination of DHEA administration and exercise training effectively improved fasting blood glucose and insulin levels, and insulin sensitivity, which may reflect increased muscular DHEA and DHT concentrations.

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

    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. Cardiac Insulin Resistance and MicroRNA Modulators

    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.

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

    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

  1. LIPID PROFILE AND ITS RATIO AS SURROGATE MARKER OF INSULIN RESISTANCE IN OBESE PATIENTS

    Senthil

    2015-11-01

    Full Text Available BACKGROUND : Insulin resistance plays a significant role in evolution of atherosclerosis and cardiovascular diseases . 1 Early assessment of this resistance will provide sufficient time in preventing this progression. The prevailing method of assessing this resistance i s cumbersome and time consuming. This study is done to assess the relationship between lipid profile (lipoproteins and insulin resistance which in turn will act as an easy marker of predicting insulin resistance in cl inical setting. OBJECTIVE: The aim of this study is to assess the correlation of lipid profile and its ratio ’ s with insulin resistance and its predictability in identifying insulin resistance. METHODS: This is a cross sectional study of 100 obese patients without diabetes. Obesity was defined by Body mass index (BMI greater than 30. Fasting blood was obtained for Lipid profile, Insulin and blood glucose. Post prandial blood was taken for blood glucose. HOMA - IR model was chosen for calculating insulin resistance. Results obtained were analysed by student ’ s t - test and Pearson ’ s correlation done for the same. RESULTS AND OBSERVAT ION: The data on analysis revealed triglycerides, triglyceride/hdl - c ratio, total cholesterol/hdl - c ratio and serum fasting insulin level were significantly higher in homa - ir>2.5 group with statistical significance, comparing with other group. CONCLUSION: Tri glycerides, triglyceride/hdl - c and total cholesterol/hdl - c ratios can be used as a simple surrogate marker of insulin resistance in clinical setting in obese non diabetic individuals.

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

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

    2015-01-01

    BACKGROUND: Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors. METHODS AND RESULTS: We identified 15,288 women from the Women's Health Initiative Biomarkers....../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...

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

    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)

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

    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)

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

    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. .

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

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

    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.

  8. Executive function and endocrinological responses to acute resistance exercise

    Chia-Liang Tsai

    2014-08-01

    Full Text Available This study had the following two aims: First, to explore the effects of acute resistance exercise (RE, i.e., using exercise machines to contract and stretch muscles on behavioral and electrophysiological performance when performing a cognitive task involving executive functioning in young male adults; Second, to investigate the potential biochemical mechanisms of such facilitative effects using two neurotrophic factors [i.e., growth hormone (GH and insulin-like growth factor-1 (IGF-1] and the cortisol levels elicited by such an exercise intervention mode with two different exercise intensities. Sixty young male adults were recruited and randomly assigned to a high-intensity (HI exercise group, moderate-intensity (MI exercise group, and non-exercise-intervention (NEI group. Blood samples were taken, and the behavioral and electrophysiological indices were simultaneously measured when individuals performed a Go/No-Go task combined with the Erikson Flanker paradigm at baseline and after either an acute bout of 30 minutes of moderate- or high-intensity RE or a control period. The results showed that the acute RE could not only benefit the subjects’ behavioral (i.e., RTs and accuracy performance, as found in previous studies, but also increase the P3 amplitude. Although the serum GH and IGF-1 levels were significantly increased via moderate or high intensity RE in both the MI and HI groups, the increased serum levels of neurotrophic factors were significantly decreased about 20 minutes after exercise. In addition, such changes were not correlated with the changes in cognitive (i.e., behavioral and electrophysiological performance. In contrast, the serum levels of cortisol in the HI and MI groups were significantly lower after acute RE, and the changes in cortisol levels were significantly associated with the changes in electrophysiological (i.e., P3 amplitude performance. The findings suggest the beneficial effects of acute RE on executive

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

    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...

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

    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...

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

    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.

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

    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)

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

    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

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

    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.

  15. Insulin resistance as a predictor of incident asthma-like symptoms in adults

    Thuesen, B H; Husemoen, L L N; Hersoug, L-G; Pisinger, C; Linneberg, A

    2009-01-01

    .6%) participated at follow-up. At baseline three obesity measures were considered: body mass index, waist circumference, and waist-to-hip ratio. In addition, fasting glucose and insulin were measured for determination of insulin resistance. Information on asthma-like symptoms at baseline and follow-up were...... associated with incident wheezing and asthma-like symptoms. In addition, insulin resistance was associated with incident wheezing [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.38-2.54] and asthma-like symptoms (OR 1.61, 95% CI 1.23-2.10). The effect of insulin resistance was stronger than that of...

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

    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.

    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

    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

    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. Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes.

    Robinson, Katherine A; Hegyi, Krisztina; Hannun, Yusuf A; Buse, Maria G; Sethi, Jaswinder K

    2014-01-01

    Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used "specific" inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not -β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway. PMID:25330241

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

    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...

  2. 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

    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...

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

    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...

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

    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...

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

    Nellemann, Birgitte; Vendelbo, Mikkel H; Nielsen, Thomas S;

    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....

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

    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...

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

    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

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

    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

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

    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....

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

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

    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

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

    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. Hyperinsulinemia improves ischemic LV function in insulin resistant subjects

    Khan Sadia N

    2010-06-01

    Full Text Available Abstract Background Glucose is a more efficient substrate for ATP production than free fatty acid (FFA. Insulin resistance (IR results in higher FFA concentrations and impaired myocardial glucose use, potentially worsening ischemia. We hypothesized that metabolic manipulation with a hyperinsulinemic euglycemic clamp (HEC would affect a greater improvement in left ventricular (LV performance during dobutamine stress echo (DSE in subjects with IR. Methods 24 subjects with normal LV function and coronary disease (CAD awaiting revascularization underwent 2 DSEs. Prior to one DSEs they underwent an HEC, where a primed infusion of insulin (rate 43 mU/m 2/min was co-administered with 20% dextrose at variable rates to maintain euglycemia. At steady-state the DSE was performed and images of the LV were acquired with tissue Doppler at each stage for offline analysis. Segmental peak systolic velocities (Vs were recorded, as well as LV ejection fraction (EF. Subjects were then divided into two groups based on their insulin sensitivity during the HEC. Results HEC changed the metabolic environment, suppressing FFAs and thereby increasing glucose use. This resulted in improved LV performance at peak stress, measured by EF (IS group mean difference 5.3 (95% CI 2.5-8 %, p = 0.002; IR group mean difference 8.7 (95% CI 5.8-11.6 %, p s in ischemic segments (IS group mean improvement 0.7(95% CI 0.07-1.58 cm/s, p = 0.07; IR group mean improvement 1.0 (95% CI 0.54-1.5 cm/s, p , that was greater in the subjects with IR. Conclusions Increased myocardial glucose use induced by HEC improves LV function under stress in subjects with CAD and IR. Cardiac metabolic manipulation in subjects with IR is a promising target for future therapy.

  14. Obese children and adolescents have elevated nighttime blood pressure independent of insulin resistance and arterial stiffness

    Hvidt, Kristian N; Olsen, Michael H; Holm, Jens-Christian;

    2014-01-01

    BACKGROUND: Insulin resistance has been related to elevated blood pressure (BP) in obese children and may adversely affect the vasculature by arterial stiffening. The objective was to investigate whether daytime and nighttime BP were elevated and related to insulin resistance and arterial stiffness...... in obese children and adolescents. METHODS: Ninety-two obese patients aged 10-18 years were compared with 49 healthy control individuals. Insulin resistance was measured as the homeostatic assessment model (HOMA), and arterial stiffness was measured as carotid-femoral pulse wave velocity (cfPWV). RESULTS...... analyses, the higher nighttime BP in the obese group was independent of logHOMA and cfPWV. CONCLUSIONS: Obese children had a higher nighttime BP when compared with the control group independently of insulin resistance and arterial stiffness. No relationship was found between insulin resistance and arterial...

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

    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...

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

    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. Insulin and fiber type in the offspring of T2DM subjects with resistance training and detraining

    Schofield, Katherine L; Rehrer, Nancy J; Perry, Tracy L; Ross, Angus; Andersen, Jesper L; Osborne, Hamish

    2012-01-01

    Effects of resistance training and detraining on glucose and insulin responses to an oral glucose load, muscle fiber type, and muscular performance in the offspring of those with type 2 diabetes (familial insulin resistant (FIR)) were investigated....

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

    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...

  19. Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity

    Beck Jørgensen, Sebastian; O'Neill, Hayley M; Sylow, Lykke;

    2013-01-01

    Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin...... of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy...... expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance....

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

    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.

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

    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

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

    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.

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

    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

  4. Effects of diet-induced weight gain and turnout to pasture on insulin sensitivity in moderately insulin resistant horses.

    Lindåse, Sanna S; Nostell, Katarina E; Müller, Cecilia E; Jensen-Waern, Marianne; Bröjer, Johan T

    2016-03-01

    OBJECTIVE To quantify insulin sensitivity and monitor glucose, insulin, and lipid concentrations in a group of moderately insulin-resistant horses during induction of obesity by use of a forage diet supplemented with fat and during subsequent turnout to pasture. ANIMALS 9 adult Standardbred mares (11 to 20 years old). PROCEDURES Weight gain of horses was induced during 22 weeks by use of a forage diet supplemented with fat fed in gradually increasing amounts, followed by feeding of that fat-supplemented diet at 2.5 times the daily maintenance requirements. Horses were then turned out to pasture. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp method before and after weight gain and after 4 weeks at pasture. Body weight, body condition score, and cresty neck score as well as fasting and postprandial concentrations of plasma insulin, plasma glucose, serum triglyceride, and serum nonesterified fatty acids were measured during the study. RESULTS Body weight typically increased by 10%, and body condition score (scale, 1 to 9) increased by > 1.5 from the start to the end of the weight-gain period. There was no difference in insulin sensitivity or metabolic clearance rate of insulin during the weight-gain period. Four weeks at pasture generally improved insulin sensitivity and metabolic clearance rate of insulin by 54% and 32%, respectively, but there was no change in body weight or body condition score. CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that dietary composition played a more important role than did short-term weight gain on alterations in insulin sensitivity of horses. PMID:26919602

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

    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.

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

    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...

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

    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

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

    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.

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

    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.

  10. Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats

    Dotzert, Michelle S.; Murray, Michael R.; McDonald, Matthew W.; Olver, T. Dylan; Velenosi, Thomas J.; Hennop, Anzel; Noble, Earl G.; Urquhart, Brad L.; Melling, C. W. James

    2016-01-01

    The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9–15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p < 0.05). There were no differences between C and DX, suggesting that exercise improved insulin resistance (p < 0.05). Metabolomics analysis revealed a significant shift in lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training. PMID:27197730

  11. Selection of the appropriate method for the assessment of insulin resistance

    Borai Anwar

    2011-11-01

    Full Text Available Abstract Insulin resistance is one of the major aggravating factors for metabolic syndrome. There are many methods available for estimation of insulin resistance which range from complex techniques down to simple indices. For all methods of assessing insulin resistance it is essential that their validity and reliability is established before using them as investigations. The reference techniques of hyperinsulinaemic euglycaemic clamp and its alternative the frequently sampled intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance. However, many simple methods, from which indices can be derived, have been assessed and validated e.g. homeostasis model assessment (HOMA, quantitative insulin sensitivity check index (QUICKI. Given the increasing number of simple indices of IR it may be difficult for clinicians and researchers to select the most appropriate index for their studies. This review therefore provides guidelines and advices which must be considered before proceeding with a study.

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

    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...

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

    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

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

    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

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

    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

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

    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.

  17. The insulin-resistant phenotype of polycystic ovary syndrome

    Svendsen, Pernille Fog; Madsbad, Sten; Nilas, Lisbeth

    2009-01-01

    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...

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

    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

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

    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.

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

    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

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

    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

  2. Susceptibility to oxidative stress, insulin resistance, and insulin secretory response in the development of diabetes from obesity

    Kocić Radivoj

    2007-01-01

    Full Text Available Background/Aim. Oxidative stress plays a critical role in the pathogenesis of various diseases. Recent reports indicate that obesity may induce systemic oxidative stress. The aim of the study was to potentiate oxidative stress as a factor which may aggravate peripheral insulin sensitivity and insulinsecretory response in obesity in this way to potentiate development of diabetes. The aim of the study was also to establish whether insulin-secretory response after glucagonstimulated insulin secretion is susceptible to prooxidant/ antioxidant homeostasis status, as well as to determine the extent of these changes. Methods. A mathematical model of glucose/insulin interactions and C-peptide was used to indicate the degree of insulin resistance and to assess their possible relationship with altered antioxidant/prooxidant homeostasis. The study included 24 obese healthy and 16 obese newly diagnozed non-insulin dependent diabetic patients (NIDDM as well as 20 control healthy subjects, matched in age. Results. Total plasma antioxidative capacity, erythrocyte and plasma reduced glutathione level were significantly decreased in obese diabetic patients, but also in obese healthy subjects, compared to the values in controls. The plasma lipid peroxidation products and protein carbonyl groups were significantly higher in obese diabetics, more than in obese healthy subjects, compared to the control healthy subjects. The increase of erythrocyte lipid peroxidation at basal state was shown to be more pronounced in obese daibetics, but the apparent difference was obtained in both the obese healthy subjects and obese diabetics, compared to the control values, after exposing of erythrocytes to oxidative stress induced by H2O2. Positive correlation was found between the malondialdehyde (MDA level and index of insulin sensitivity (FIRI. Conclusion. Increased oxidative stress together with the decreased antioxidative defence seems to contribute to decreased insulin

  3. Association of chronic viral hepatitis B with insulin resistance

    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

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

    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

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

    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

  6. Carnitine Palmitoyltransferase 1b Deficient Mice Develop Severe Insulin Resistance After Prolonged High Fat Diet Feeding

    Kim, Teayoun; Moore, John F.; Sharer, Jon D.; Yang, Kevin; Wood, Philip A.; Yang, Qinglin

    2014-01-01

    Background Carnitine palmitoyltransferase 1 (CPT1) is the rate-limiting enzyme governing the entry of long-chain acyl-CoAs into mitochondria. Treatments with CPT1 inhibitors protect against insulin resistance in short-term preclinical animal studies. We recently reported that mice with muscle isoform CPT1b deficiency demonstrated improved insulin sensitivity when fed a High Fat-Diet (HFD) for up to 5 months. In this follow up study, we further investigated whether the insulin sensitizing effe...

  7. Subjective Sleep Complaints Are Associated With Insulin Resistance in Individuals Without Diabetes

    Pyykkönen, Antti-Jussi; Isomaa, Bo; Pesonen, Anu-Katriina; Johan G. Eriksson; Groop, Leif; Tuomi, Tiinamaija; Räikkönen, Katri

    2012-01-01

    OBJECTIVE Sleep disorders and subjective sleep complaints have been associated with increased risk of type 2 diabetes. The evidence with respect to insulin resistance (IR) and insulin secretion in individuals without type 2 diabetes has been scarce and elusive. We examined if subjective sleep complaints and their co-occurrence were associated with IR and insulin secretion in adult women and men without diabetes. RESEARCH DESIGN AND METHODS Women (n = 442) and men (n = 354) 18–75 years of age ...

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

    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, ...

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

    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...

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

    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...

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

    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)

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

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

    2008-01-01

    Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling. Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance. Using SOCS-1 knockout mice, we...... investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD). SOCS-1 knockout mice on HFD gained 70% more weight, displayed a 2.3-fold increase in epididymal fat pads mass and increased hepatic lipid content. This was accompanied by increased mRNA expression...... 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...

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

    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.

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

    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.

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

    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.

  16. Effect of a p38 MAPK inhibitor on FFA-induced hepatic insulin resistance in vivo.

    Pereira, S; Yu, W Q; Moore, J; Mori, Y; Tsiani, E; Giacca, A

    2016-01-01

    The mechanisms whereby prolonged plasma free fatty acids elevation, as found in obesity, causes hepatic insulin resistance are not fully clarified. We herein investigated whether inhibition of p38 mitogen-activated protein kinase (MAPK) prevented hepatic insulin resistance following prolonged lipid infusion. Chronically cannulated rats were subdivided into one of four intravenous (i.v.) treatments that lasted 48 h: Saline (5.5 μl min(-1)), Intralipid plus heparin (IH, 20% Intralipid+20 U ml(-1) heparin; 5.5 μl min(-1)), IH+p38 MAPK inhibitor (SB239063) and SB239063 alone. During the last 2 h of treatment, a hyperinsulinemic (5 mU kg(-1) min(-1)) euglycemic clamp together with [3-(3)H] glucose methodology was carried out to distinguish hepatic from peripheral insulin sensitivity. We found that SB239063 prevented IH-induced hepatic insulin resistance, but not peripheral insulin resistance. SB239063 also prevented IH-induced phosphorylation of activating transcription factor 2 (ATF2), a marker of p38 MAPK activity, in the liver. Moreover, in another lipid infusion model in mice, SB239063 prevented hepatic but not peripheral insulin resistance caused by 48 h combined ethyloleate plus ethylpalmitate infusion. Our results suggest that inhibition of p38 MAPK may be a useful strategy in alleviating hepatic insulin resistance in obesity-associated disorders. PMID:27136448

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

    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.

  18. Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice.

    Keung, Wendy; Ussher, John R; Jaswal, Jagdip S; Raubenheimer, Monique; Lam, Victoria H M; Wagg, Cory S; Lopaschuk, Gary D

    2013-03-01

    Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to insulin resistance and glucose intolerance. However, increasing muscle fatty acid oxidation may cause a reciprocal decrease in glucose oxidation, which might impair insulin sensitivity and glucose tolerance. We therefore investigated what effect inhibition of mitochondrial fatty acid uptake has on whole-body glucose tolerance and insulin sensitivity in obese insulin-resistant mice. C57BL/6 mice were fed a high-fat diet (60% calories from fat) for 12 weeks to develop insulin resistance. Subsequent treatment of mice for 4 weeks with the carnitine palmitoyltransferase-1 inhibitor, oxfenicine (150 mg/kg i.p. daily), resulted in improved whole-body glucose tolerance and insulin sensitivity. Exercise capacity was increased in oxfenicine-treated mice, which was accompanied by an increased respiratory exchange ratio. In the gastrocnemius muscle, oxfenicine increased pyruvate dehydrogenase activity, membrane GLUT4 content, and insulin-stimulated Akt phosphorylation. Intramyocellular levels of lipid intermediates, including ceramide, long-chain acyl CoA, and diacylglycerol, were also decreased. Our results demonstrate that inhibition of mitochondrial fatty acid uptake improves insulin sensitivity in diet-induced obese mice. This is associated with increased carbohydrate utilization and improved insulin signaling in the skeletal muscle, suggestive of an operating Randle Cycle in muscle. PMID:23139350

  19. Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor

    Zhang, Chongben; Cooper, Daniel E; Grevengoed, Trisha J;

    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...

  20. Rosiglitazone-Mediated Effects on Skeletal Muscle Gene Expression Correlate with Improvements in Insulin Sensitivity in Individuals with HIV-Insulin Resistance

    Gelato, Marie C.; Vosswinkel, James A.; Melendez, Mark M; McNurlan, Margaret A.; Mynarcik, Dennis C.

    2011-01-01

    Rosiglitazone, an agonist of peroxisome proliferator activated receptor (PPARγ), improves insulin sensitivity by increasing insulin-stimulated glucose uptake into muscle tissue. This study was undertaken to assess changes in expression of PPAR-regulated genes in muscle tissue following treatment of HIV-associated insulin resistance with rosiglitazone. Muscle gene expression was assessed in twenty-two seronegative HIV subjects (control), 21 HIV-infected individuals with normal insulin sensitiv...

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

    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,

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

    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.

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

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

    1999-01-01

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

  4. Hypertension association with serum lipoproteins, insulin, insulin resistance and C-peptide: Unexplored forte of cardiovascular risk in hypothyroidism

    Purvi Purohit

    2013-01-01

    Full Text Available Background: There is a gross dearth of correlative data for cardiovascular diseases. Aim: We aimed to explore the association of systolic and diastolic blood pressure with anthropometric and biochemical parameters of hypothyroid patients in order to establish any correlation that may exist and be useful in an early diagnosis and management against cardiovascular risk. Materials and Methods: The study included 100 healthy controls and 150 newly diagnosed hypothyroid patients. Subjects were evaluated anthropometrically and biochemically for fasting blood sugar, triiodothyronine, thyroxine, thyroid stimulating hormone, Insulin, C-peptide, lipid profile, apo-B and apo-A 1 . The results were statistically analysed using unpaired t-test and Spearman′s coefficient of Correlation. Results: The hypothyroids had a female preponderance (73.3% however; their biochemical profiles were comparable with those of male counterparts. They had raised Body Mass Index, hypertension, hyperinsulinemia, insulin resistance, raised C-peptide, dyslipidaemia with raised apo-B and reduced apo-A 1 and strong association of systolic and diastolic blood pressure with insulin, insulin resistance, C-peptide and Total cholesterol/HDLc (TC/HDLc. Conclusion: Strong association of hypertension with serum insulin, IR, C -peptide and TC/HDLc hints significant contribution towards cardiovascular risk in hypothyroid adults of Jodhpur.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  10. 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.

    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...

  11. Pharyngeal collapsibility during sleep is elevated in insulin-resistant females with morbid obesity.

    Llanos, Oscar L; Galiatsatos, Panagis; Guzmán-Vélez, Edmarie; Patil, Susheel P; Smith, Philip L; Magnuson, Thomas; Schweitzer, Michael; Steele, Kimberley; Polotsky, Vsevolod Y; Schwartz, Alan R

    2016-06-01

    Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea.90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) >10 events·h(-1), diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, Pcritp ) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to Pcritp Groups with high Pcritp compared to low Pcritp did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high Pcritp group compared to the low Pcritp group (pObese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility. PMID:27103392

  12. Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats.

    Dotzert, Michelle S; Murray, Michael R; McDonald, Matthew W; Olver, T Dylan; Velenosi, Thomas J; Hennop, Anzel; Noble, Earl G; Urquhart, Brad L; Melling, C W James

    2016-01-01

    The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9-15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training. PMID:27197730

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

    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.

  14. Role of insulin resistance and diet in acne

    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...

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

    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...

  16. 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

    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.

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

    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. Microbial Translocation in HIV Infection is Associated with Dyslipidemia, Insulin Resistance, and Risk of Myocardial Infarction

    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....

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

    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.

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

    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

  1. Pid1 induces insulin resistance in both human and mouse skeletal muscle during obesity.

    Bonala, Sabeera; McFarlane, Craig; Ang, Jackie; Lim, Radiance; Lee, Marcus; Chua, Hillary; Lokireddy, Sudarsanareddy; Sreekanth, Patnam; Leow, Melvin Khee Shing; Meng, Khoo Chin; Shyong, Tai E; Lee, Yung Seng; Gluckman, Peter D; Sharma, Mridula; Kambadur, Ravi

    2013-09-01

    Obesity is associated with insulin resistance and abnormal peripheral tissue glucose uptake. However, the mechanisms that interfere with insulin signaling and glucose uptake in human skeletal muscle during obesity are not fully characterized. Using microarray, we have identified that the expression of Pid1 gene, which encodes for a protein that contains a phosphotyrosine-interacting domain, is increased in myoblasts established from overweight insulin-resistant individuals. Molecular analysis further validated that both Pid1 mRNA and protein levels are increased in cell culture models of insulin resistance. Consistent with these results, overexpression of phosphotyrosine interaction domain-containing protein 1 (PID1) in human myoblasts resulted in reduced insulin signaling and glucose uptake, whereas knockdown of PID1 enhanced glucose uptake and insulin signaling in human myoblasts and improved the insulin sensitivity following palmitate-, TNF-α-, or myostatin-induced insulin resistance in human myoblasts. Furthermore, the number of mitochondria in myoblasts that ectopically express PID1 was significantly reduced. In addition to overweight humans, we find that Pid1 levels are also increased in all 3 peripheral tissues (liver, skeletal muscle, and adipose tissue) in mouse models of diet-induced obesity and insulin resistance. An in silico search for regulators of Pid1 expression revealed the presence of nuclear factor-κB (NF-κB) binding sites in the Pid1 promoter. Luciferase reporter assays and chromatin immunoprecipitation studies confirmed that NF-κB is sufficient to transcriptionally up-regulate the Pid1 promoter. Furthermore, we find that myostatin up-regulates Pid1 expression via an NF-κB signaling mechanism. Collectively these results indicate that Pid1 is a potent intracellular inhibitor of insulin signaling pathway during obesity in humans and mice. PMID:23927930

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

    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

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

    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.

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

    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.

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

    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...

  6. Short-Term Exercise Training Improves Insulin Sensitivity but Does Not Inhibit Inflammatory Pathways in Immune Cells from Insulin-Resistant Subjects

    Sara M. Reyna; Tantiwong, Puntip; Cersosimo, Eugenio; DeFronzo, Ralph A; Sriwijitkamol, Apiradee; Musi, Nicolas

    2013-01-01

    Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for ...

  7. The relationship between rosacea and insulin resistance and metabolic syndrome.

    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 (prosacea and IR and some parameters of cardiovascular risk factors. We recommend investigation of IR in rosacea patients. PMID:27328660

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

    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

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

    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

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

    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.

  11. Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance

    Emanuelli, Brice; Eberlé, Delphine; Suzuki, Ryo;

    2008-01-01

    Insulin resistance, a hallmark of type 2 diabetes and obesity, is associated with increased activity of MAP and stress-activated protein (SAP) kinases, which results in decreased insulin signaling. Our goal was to investigate the role of MAP kinase phosphatase-4 (MKP-4) in modulating this process......, improved glucose intolerance, decreased expression of gluconeogenic and lipogenic genes, and reduced hepatic steatosis. Thus, MKP-4 has a protective effect against the development of insulin resistance through its ability to dephosphorylate and inactivate crucial mediators of stress-induced insulin...... resistance, such as ERK and JNK, and increasing MKP-4 activity might provide a therapy for insulin-resistant disorders....

  12. Mechanisms Linking the Metabolic Syndrome and Cardiovascular Disease: Role of Hepatic Insulin Resistance

    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...

  13. The Relation between Birth Weight and Insulin Resistance in Korean Adolescents

    Kim, Chul-Sik; Park, Jong-Suk; Park, Jina; Nam, Ji-Sun; Kang, Eun-Seok; Ahn, Chul-Woo; Cha, Bong-Soo; Lim, Sung-Kil; Kim, Kyung-Rae; Lee, Hyun-chul; Huh, Kap-Bum; Kim, Dae-Jung

    2006-01-01

    Low birth weight is associated with insulin resistance and type 2 diabetes in adults. The fetal programming hypothesis has shown that insulin resistance and its associated metabolic disturbances result from a poor gestational environment, for which low birth weight is a surrogate. An at-home questionnaire survey was performed on 660 middle school students (12-15 years) in Seoul, Korea, and 152 cases were randomly selected based on their birth weight. Subjects were divided into three groups ac...

  14. An investigation into genetic contribution to the relationship between insulin resistance and birth weight

    Jahan, Samsad; Zinnat, Rahelee; Hasan, Zahid; Ahmed, Chowdhury Meshkat; Habib, Samira Humaria; Saha, Soma; Ali, Liaquat

    2009-01-01

    BACKGROUND: Insulin resistance has been proposed to be the most likely phenotypic trait that could represent a genetic link between low birth weight and type 2 diabetes, especially in Southeast Asia. Insulin resistance can persist for many years, even decades, before the manifestation of overt diabetes. There have been many studies suggesting a strong genetic basis in the etiology of type 2 diabetes mellitus. There is also ample evidence providing a link with low birth weight and type 2 diabe...

  15. Association between Serum Leptin Concentrations and Insulin Resistance: A Population-Based Study from China

    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...

  16. Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity

    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...

  17. Fitness versus Fatness and Insulin Resistance in U.S. Adolescents

    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...

  18. Serum Autotaxin/ENPP2 Correlates with Insulin Resistance in Older Humans with Obesity

    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 ...

  19. ANTIDIABETIC AND HYPOLIPIDEMIC ACTIVITY OF GYMNEMA SYLVESTRE IN DEXAMETHASONE INDUCED INSULIN RESISTANCE IN ALBINO RATS

    Hemanth Kumar V, Nagendra Nayak IM , Shobha V Huilgol, Saeed M Yendigeri , Narendar K

    2015-01-01

    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 M...

  20. Angiotensin II Receptor Blocker Ameliorates Stress-Induced Adipose Tissue Inflammation and Insulin Resistance

    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...

  1. On the importance of fat cell size, location and signaling in insulin resistance

    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...

  2. Inflammatory Induction of Human Resistin Causes Insulin Resistance in Endotoxemic Mice

    Park, Hyeong-Kyu; Qatanani, Mohammed; Briggs, Erika R.; Ahima, Rexford S.; Lazar, Mitchell A.

    2011-01-01

    OBJECTIVE Although adipocyte-derived murine resistin links insulin resistance to obesity, the role of human resistin, predominantly expressed in mononuclear cells and induced by inflammatory signals, remains unclear. Given the mounting evidence that obesity and type 2 diabetes are inflammatory diseases, we sought to determine the relationship between inflammatory increases in human resistin and insulin resistance. RESEARCH DESIGN AND METHODS To investigate the role of human resistin on glucos...

  3. Blood Mercury and Insulin Resistance in Nondiabetic Koreans (KNHANES 2008-2010)

    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...

  4. Oxidative Stress: A Potential Recipe For Anxiety, Hypertension and Insulin Resistance

    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...

  5. Insulin Resistance Is an Important Risk Factor for Cognitive Impairment in Elderly Patients with Primary Hypertension

    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 ...

  6. Decreased Skin-Mediated Detoxification Contributes to Oxidative Stress and Insulin Resistance

    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...

  7. Dietary glycemic index, glycemic load, fiber, simple sugars, and insulin resistance

    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....

  8. Link between insulin resistance and hypertension: What is the evidence from evolutionary biology?

    Zhou, Ming-Sheng; Wang, Aimei; Hong YU

    2014-01-01

    Insulin resistance and hypertension are considered as prototypical “diseases of civilization” that are manifested in the modern environment as plentiful food and sedentary life. The human propensity for insulin resistance and hypertension is a product, at least in part, of our evolutionary history. Adaptation to ancient lifestyle characterized by a low sodium, low-calorie food supply and physical stress to injury response has driven our evolution to shape and preserve a thrifty genotype, whic...

  9. INFLUENCE OF HERBAL EXTRACTS ON METABOLIC DISTURBANCES IN DIABETES MELLITUS AND INSULIN RESISTANCE MODEL

    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...

  10. Effect of Vitamin K Supplementation on Insulin Resistance in Older Men and Women

    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 ...

  11. Severe insulin resistance treatment with intravenous chromium in septic shock patient

    2012-01-01

    Insulin resistance has been well documented in critically ill patients. Adequate blood sugar control has been associated with better wound healing, and better outcomes in selected patient populations. Chromium is an essential component of human diet. It is believed to affect changes in glucose uptake. Several studies have shown beneficial effects of oral chromium in diabetic patients with insulin resistance, but role of intravenous chromium infusion has not been completely evaluated. We prese...

  12. Adiponectin is associated with risk of the metabolic syndrome and insulin resistance in women

    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...

  13. Waist circumference and insulin resistance: a cross-sectional study of Japanese men

    Hamachi Tadamichi

    2009-01-01

    Full Text Available Abstract Background Visceral obesity is positively related to insulin resistance. The nature of the relationship between waist circumference and insulin resistance has not been known in Japanese populations. This study examined the relationship between waist circumference and insulin resistance and evaluated the optimal cutoff point for waist circumference in relation to insulin resistance in middle-aged Japanese men. Methods Study subjects included 4800 Japanese men aged 39 to 60 years. Insulin resistance was evaluated by the homeostasis model assessment of insulin resistance (HOMA-IR. The relationship of waist circumference with HOMA-IR was assessed by use of adjusted means of HOMA-IR and odds ratios of elevated HOMA-IR defined as the highest quintile (≥2.00. Receiver operating characteristics (ROC curve analysis using Youden index and the area under curve (AUC was employed to determine optimal cutoffs of waist circumference in relation to HOMA-IR. Results Adjusted geometric means of HOMA-IR and prevalence odds of elevated HOMA-IR were progressively higher with increasing levels of waist circumference. In the ROC curve analysis, the highest value of Youden index was obtained for a cutoff point of 85 cm in waist circumference across different values of HOMA-IR. Multiple logistic regression analysis also indicated that the AUC was consistently the largest for a waist circumference of 85 cm. Conclusion Waist circumference is linearly related to insulin resistance, and 85 cm in waist circumference is an optimal cutoff in predicting insulin resistance in middle-aged Japanese men.

  14. Predicting insulin resistance using the triglyceride-to-high-density lipoprotein cholesterol ratio in Taiwanese adults

    Lai Ning-Sheng; Chiang Jui-Kun; Chang Jiunn-Kae; Koo Malcolm

    2011-01-01

    Abstract Background The triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) has been advocated as a simple clinical indicator of insulin resistance. Thresholds of TG/HDL-C appeared to depend on ethnicity. However, no studies have specifically compared the accuracy of TG/HDL-C with and without other clinical and demographic factors in predicting insulin resistance in Taiwanese adults. The aim of the present investigation was to use TG/HDL-C and other clinical available factor...

  15. Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver

    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

  16. Association of obesity and insulin resistance with dyslipidemia in Indian women with polycystic ovarian syndrome

    Kalra Anuradha

    2006-11-01

    Full Text Available BACKGROUND: Dyslipidemia, diabetes and obesity are all potent cardiovascular risk factors that tend to cluster in women with polycystic ovary syndrome (PCOS. Metabolic disorders in patients with PCOS cannot be explained solely by the presence of obesity. OBJECTIVE: To study the correlation between insulin resistance and serum lipid profile in Indian women with PCOS. SETTING: Gynecology clinic of a tertiary care hospital. MATERIALS AND METHODS: In this prospective study done from April 2004 to December 2004, 65 women with PCOS had their body mass index (BMI and waist hip ratio calculated. Fasting glucose, insulin and lipid profiles were also estimated in each case. Insulin resistance was defined by fasting glucose-to-insulin ratio £ 4.5. The association of obesity markers and insulin resistance with lipid parameters was then studied. Statistical analysis using student ′t′ and Mann Whitney U tests was done as indicated. RESULTS: Insulin resistance was seen in 50 of the 65 PCOS women. There was no correlation seen between markers of obesity such as BMI and waist/hip ratio with various lipid parameters. But in PCOS women with insulin resistance, the lipid profile was significantly different [high triglycerides, total cholesterol and lower high-density lipoprotein (HDL] compared to insulin-sensitive women. The difference between the two groups for total cholesterol (P = 0.002, triglycerides (P = < 0.001 and HDL (P = < 0.001 was statistically significant but that for low-density lipoprotein (LDL (P = 0.07 was not statistically significant. CONCLUSION: Insulin resistance is associated with dyslipidemia in women with PCOS, independent of obesity.

  17. Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats.

    Castro, Gisele; C Areias, Maria Fernanda; Weissmann, Lais; Quaresma, Paula G F; Katashima, Carlos K; Saad, Mario J A; Prada, Patricia O

    2013-01-01

    Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala. PMID:24251109

  18. Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats☆

    Castro, Gisele; C. Areias, Maria Fernanda; Weissmann, Lais; Quaresma, Paula G.F.; Katashima, Carlos K.; Saad, Mario J.A.; Prada, Patricia O.

    2013-01-01

    Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala. PMID:24251109

  19. IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

    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...

  20. IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

    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...

  1. Relationship between blood pressure and insulin resistance in patients with gestational diabetes

    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)

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

    Nielsen, R.; Wiggers, Henrik; Halbirk, Mads;

    2012-01-01

    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...... 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....... Hypoglycemia was common and may limit the use of GLP-1 in these patients. Insulin sensitivity, lipid-, and protein metabolism remained unchanged.Data were collected at the examinational laboratories of Department of Endocrinology and Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark....

  3. Effects of Portulaca Oleracea on Insulin Resistance in Rats with Type 2 Diabetes Mellitus

    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. Does Diacylglycerol Accumulation in Fatty Liver Disease Cause Hepatic Insulin Resistance?

    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.

  5. Does Diacylglycerol Accumulation in Fatty Liver Disease Cause Hepatic Insulin Resistance?

    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

  6. JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity.

    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

  7. Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats

    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...

  8. Investigation of insulin resistance in narcoleptic patients: dependent or independent of body mass index?

    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

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

    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.

  10. Exercise Intensity Modulates Glucose-Stimulated Insulin Secretion when Adjusted for Adipose, Liver and Skeletal Muscle Insulin Resistance

    Malin, Steven K.; Rynders, Corey A.; Weltman, Judy Y.; Barrett, Eugene J.; Weltman, Arthur

    2016-01-01

    Little is known about the effects of exercise intensity on compensatory changes in glucose-stimulated insulin secretion (GSIS) when adjusted for adipose, liver and skeletal muscle insulin resistance (IR). Fifteen participants (8F, Age: 49.9±3.6yr; BMI: 31.0±1.5kg/m2; VO2peak: 23.2±1.2mg/kg/min) with prediabetes (ADA criteria, 75g OGTT and/or HbA1c) underwent a time-course matched Control, and isocaloric (200kcal) exercise at moderate (MIE; at lactate threshold (LT)), and high-intensity (HIE; 75% of difference between LT and VO2peak). A 75g OGTT was conducted 1 hour post-exercise/Control, and plasma glucose, insulin, C-peptide and free fatty acids were determined for calculations of skeletal muscle (1/Oral Minimal Model; SMIR), hepatic (HOMAIR), and adipose (ADIPOSEIR) IR. Insulin secretion rates were determined by deconvolution modeling for GSIS, and disposition index (DI; GSIS/IR; DISMIR, DIHOMAIR, DIADIPOSEIR) calculations. Compared to Control, exercise lowered SMIR independent of intensity (P<0.05), with HIE raising HOMAIR and ADIPOSEIR compared with Control (P<0.05). GSIS was not reduced following exercise, but DIHOMAIR and DIADIPOSEIR were lowered more following HIE compared with Control (P<0.05). However, DISMIR increased in an intensity based manner relative to Control (P<0.05), which corresponded with lower post-prandial blood glucose levels. Taken together, pancreatic insulin secretion adjusts in an exercise intensity dependent manner to match the level of insulin resistance in skeletal muscle, liver and adipose tissue. Further work is warranted to understand the mechanism by which exercise influences the cross-talk between tissues that regulate blood glucose in people with prediabetes. PMID:27111219

  11. Relationship among resistance to the insulin and obesity in Zacatecas population

    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)

  12. Insulin secretion in lipodystrophic HIV-infected patients is associated with high levels of nonglucose secretagogues and insulin resistance of beta-cells

    Haugaard, Steen B; Andersen, Ove; Storgaard, Heidi;

    2004-01-01

    We examined whether plasma concentrations of nonglucose insulin secretagogues are associated with prehepatic insulin secretion rates (ISR) in nondiabetic, insulin-resistant, human immunodeficiency virus (HIV)-infected, lipodystrophic patients (LIPO). Additionally, the negative feedback of insulin...... on ISR was evaluated. ISR were estimated by deconvolution of plasma C-peptide concentrations during fasting (basal) and during the last 30 min of a 120-min euglycemic insulin clamp (40 mU.m(-2).min(-1)). Eighteen normoglycemic LIPO were compared with 25 normoglycemic HIV-infected patients without...... lipodystrophy (controls). Thirty minutes before start of the clamp, a bolus of glucose was injected intravenously to stimulate endogenous insulin secretion. Insulin sensitivity index (SiRd) was estimated from glucose tracer analysis. LIPO displayed increased basal ISR (69%), clamp ISR (114%), basal insulin (130...

  13. INSULIN AND INSULIN RESISTANCE: NEW MOLECULE MARKERS AND TARGET MOLECULE FOR THE DIAGNOSIS AND THERAPY OF DISEASES OF THE CENTRAL NERVOUS SYSTEM

    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.

  14. Does cardiorespiratory fitness modify the association between birth weight and insulin resistance in adult life?

    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.

  15. Resistance to the antilipolytic effect of insulin in adipocytes of African-American compared to Caucasian postmenopausal women

    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...

  16. Cutoff Values of Surrogate Measures of Insulin Resistance for Metabolic Syndrome in Korean Non-diabetic Adults

    Lee, Sihoon; Choi, Sunghee; Kim, Hae Jin; Chung, Yoon-Sok; Lee, Kwan Woo; Lee, Hyun Chul; Huh, Kap Bum; Kim, Dae Jung

    2006-01-01

    We investigated the cutoff values of surrogate of insulin resistance for diagnosing metabolic syndrome in Korean adults. The data from 976 non-diabetic individuals (484 men and 492 women) aged 30-79 yr were analyzed. We determined the odds ratios for the prevalence of metabolic syndrome according to the quartiles of fasting insulin, homeostasis model for insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) as independent variables, while adjusting for age, s...

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

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

    2015-01-01

    Acute infusion of glucagon-like-peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. High fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether this......-mediated glucose uptake in skeletal muscle by 90% (P<0.05) after 5 days HF diet but not after 8 weeks. The present study demonstrates that GLP-1 increases MVR in rat skeletal muscle and can reverse early stages of HF diet induced insulin resistance in vivo. This article is protected by copyright. All rights...

  18. Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

    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)

  19. GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance

    Biensø, Rasmus Sjørup; Jørgensen, Stine Ringholm; Kiilerich, Kristian;

    2012-01-01

    To elucidate the molecular mechanisms behind physical inactivity-induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both...... than before bed rest. This bed rest-induced insulin resistance occurred together with reduced muscle GLUT4, hexokinase II, protein kinase B/Akt1, and Akt2 protein level, and a tendency for reduced 3-hydroxyacyl-CoA dehydrogenase activity. The ability of insulin to phosphorylate Akt and activate....... The present findings demonstrate that physical inactivity-induced insulin resistance in muscle is associated with lower content/activity of key proteins in glucose transport/phosphorylation and storage....

  20. Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women.

    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

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

    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.

  2. Influence of Acupuncture on Insulin Resistance in Simple Obesity Patients

    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

  3. STEAROYL-CoA DESATURASE-1 DEFICIENCY ATTENUATES OBESITY AND INSULIN RESISTANCE IN LEPTIN-RESISTANT OBESE MICE

    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...

  4. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    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.

  5. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    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

  6. Role of insulin resistance and diet in acne.

    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

    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. Impaired translocation of GLUT4 results in insulin resistance of atrophic soleus muscle.

    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. PMID:25713812

  9. Relationship between insulinase activity of erythrocytes and insulin resistance in patients with type 2 diabetes mellitus

    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.

  10. Study on the Relationship between Insulin-Resistance and Syndrome Differentiation Typing in Hypertension Patients

    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.

  11. The Relationship between Serum 25-Hydroxyvitamin D Concentration, Cardiorespiratory Fitness, and Insulin Resistance in Japanese Men

    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.

  12. Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action

    Varma, Vijayalakshmi; Yao-Borengasser, Aiwei; Rasouli, Neda; Nolen, Greg T.; Phanavanh, Bounleut; Starks, Tasha; Gurley, Cathy; Simpson, Pippa; McGehee, Robert E.; Kern, Philip A.; Peterson, Charlotte A.

    2009-01-01

    Obesity is characterized by adipose tissue expansion as well as macrophage infiltration of adipose tissue. This results in an increase in circulating inflammatory cytokines and nonesterified fatty acids, factors that cause skeletal muscle insulin resistance. Whether obesity also results in skeletal muscle inflammation is not known. In this study, we quantified macrophages immunohistochemically in vastus lateralis biopsies from eight obese and eight lean subjects. Our study demonstrates that m...

  13. Lipid-induced cell stress and insulin resistance

    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...

  14. Recent Advances in Obesity-Induced Inflammation and Insulin Resistance

    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...

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

    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...

  16. Adiposity, Biological Markers of Disease, and Insulin Resistance in Mexican American Adolescents, 2004-2005

    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.

  17. Insulin resistance, adiponectin and adverse outcomes following elective cardiac surgery: a prospective follow-up study

    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

  18. Insulin resistance in H pylori infection and its association with oxidative stress

    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.

  19. Predicting insulin resistance using the triglyceride-to-high-density lipoprotein cholesterol ratio in Taiwanese adults

    Lai Ning-Sheng

    2011-10-01

    Full Text Available Abstract Background The triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C has been advocated as a simple clinical indicator of insulin resistance. Thresholds of TG/HDL-C appeared to depend on ethnicity. However, no studies have specifically compared the accuracy of TG/HDL-C with and without other clinical and demographic factors in predicting insulin resistance in Taiwanese adults. The aim of the present investigation was to use TG/HDL-C and other clinical available factors to predict insulin resistance in Taiwanese adults. Methods A total of 812 subjects were recruited from at the time of their general health examination at the Buddhist Dalin Tzu Chi General Hospital, Taiwan. Demographic information and clinical characteristics were obtained. Insulin resistance was defined by the homeostasis model assessment for insulin resistance (HOMA-IR. Simple and multiple logistic regression analyses were used to obtain probabilities of insulin resistance (HOMA-IR > 2 using TG/HDL-C with (Model 2 and without (Model 1 other clinical variables. A receiver operating characteristic (ROC analysis was conducted to evaluate the ability of the two models to correctly discriminate between subjects of low and elevated HOMA-IR. Results Female sex, greater waist circumferences, and higher ALT levels were significantly associated with the risk of elevated HOMA-IR in addition to TG/HDL-C in the multiple logistic regression (Model 2. The area under the ROC curve (AUC of Model 2 was 0.71 [95% CI = 0.67-0.75] and was significantly higher (P = 0.007 than the AUC 0.66 [95% CI = 0.62-0.71] of Model 1. Conclusions The diagnostic accuracy of insulin resistance, defined by HOMA-IR, using TG/HDL-C can be significantly enhanced by including three additional clinically available factors - sex, waist circumferences, and ALT levels.

  20. Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide following acute necrotizing experimental pancreatitis

    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

  1. Correlation between maternal weight and insulin resistance in second half of pregnancy

    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.

  2. A Study on the Factors influencing insulin resistance in obese adolescents

    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

  3. Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

    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.

  4. Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH).

    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

  5. Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance

    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...

  6. Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation

    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...

  7. Fructose-fed rhesus monkeys: A nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes

    Bremer, Andrew A; Stanhope, Kimber L.; Graham, James L.; Cummings, Bethany P.; Wang, Wenli; Saville, Benjamin R.; Havel, Peter J.

    2011-01-01

    The incidence of insulin resistance has increased dramatically over the past several years, and we and others have proposed that this increase may at least in part be attributable to increased dietary fructose consumption. However, a major limitation to the study of diet-induced insulin resistance is the lack of relevant animal models. Numerous studies, mostly in rodents, have demonstrated that diets high in fructose induce insulin resistance; however, important metabolic differences exist be...

  8. 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective changes in body weight and insulin resistance

    Koska, Juraj; de Courten, Barbora; Wake, Deborah J;

    2006-01-01

    Increased mRNA and activity levels of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in human adipose tissue (AT) are associated with obesity and insulin resistance. The aim of our study was to investigate whether 11betaHSD1 expression or activity in abdominal subcutaneous AT of non......-diabetic subjects are associated with subsequent changes in body weight and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)]....

  9. Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor

    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...

  10. Insulin Resistance and Increased Muscle Cytokine Levels in Patients With Mitochondrial Myopathy

    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 AND......), identically in P and C. No differences existed in plasma cytokine concentrations. CONCLUSIONS: In patients with a variety of mitochondrial myopathies, insulin sensitivity of muscle, adipose tissue, and pancreatic A cells is reduced, supporting that mitochondrial function influences insulin action. Furthermore...... 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...

  11. Acute ablation of PERK results in ER dysfunctions followed by reduced insulin secretion and cell proliferation

    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.

  12. Does insulin resistance drive the association between hyperglycemia and cardiovascular risk?

    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

  13. Determination of Insulin Resistance and Beta Cell Function in Healthy Obese and Non-obese Individuals

    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)

  14. Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

    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.

  15. Hepatic Insulin Resistance Following Chronic Activation of the CREB Coactivator CRTC2

    Hogan, Meghan F; Ravnskjaer, Kim; Matsumura, Shigenobu;

    2015-01-01

    and dephosphorylation of the cAMP regulated CREB coactivators CRTC2 and CRTC3. In parallel, decreases in circulating insulin also increase gluconeogenic gene expression via the de-phosphorylation and activation of the forkhead transcription factor FOXO1. Hepatic gluconeogenesis is increased in insulin resistance where...... accompanying decreases in FOXO1 activity, hepatic gluconeogenic gene expression remained elevated in CRTC2S171,275A mice demonstrating that chronic increases in CRTC2 activity in the liver are indeed sufficient to promote hepatic insulin resistance and to disrupt glucose homeostasis....... increased gluconeogenic gene expression under fasting as well as feeding conditions. Circulating glucose concentrations were constitutively elevated in CRTC2S171,275A expressing mice, leading to compensatory increases in circulating insulin concentrations that enhance FOXO1 phosphorylation. Despite...

  16. The Effect of Different Doses of Vitamin D Supplementation on Insulin Resistance in ovariectomized rats

    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.

  17. Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity

    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...

  18. Intestine-targeted DGAT1 inhibition improves obesity and insulin resistance without skin aberrations in mice.

    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.

  19. Adipokines and Insulin Resistance in Young Adult Survivors of Childhood Cancer

    Latoch, Eryk; Muszynska-Roslan, Katarzyna; Panas, Agata; Panasiuk, Anna; Sawicka-Zukowska, Malgorzata; Zelazowska-Rutkowska, Beata; Zabrocka, Ewa; Krawczuk-Rybak, Maryna

    2016-01-01

    We examined the association between adipokines (leptin, adiponectin, and resistin), radiotherapy, measurement of body fat, and insulin resistance among young adult survivors of childhood cancer (CCS). Materials and Methods. Seventy-six survivors were included (mean age 24.1 ± 3.5 years). Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA-IR). The serum levels of adipokines were assayed by immunoassays. Fat mass was evaluated by DXA. Results. Mean adiponectin level and mean body FAT were higher in the examined females than in males (10009 ± 6367 ng/mL versus 6433 ± 4136 ng/mL, p < 0.01; 35.98 ± 9.61% versus 22.7 ± 7.46%, p < 0.001). Among CCS, one of 75 patients met the criteria of insulin resistance, and in 14 patients there was impaired fasting glucose. The multiple regression model for females showed that leptin/adiponectin ratio (LA ratio) significantly affected HOMA-IR (increase of 0.024 per each unit of LA ratio; p < 0.05). Radiotherapy had no effect on serum adipokines and IR. Conclusion. The observed results support the hypothesis that adiponectin might be associated with insulin resistance and it can not be ruled out that changes in the mean level of adiponectin per FAT mass or leptin/adiponectin ratio may precede the occurrence of insulin resistance in the future.

  20. [Gestational and non-gestational factors for perinatal programming of insulin resistance].

    Varadinova, M; Metodieva, R; Boyadjieva, N

    2014-01-01

    Insulin resistance is well known problem in type 2 diabetes mellitus (T2DM). Various factors play roles in the mechanisms of prenatal programming of insulin resistance. Gestational or non-gestational factors are illustrated in the present paper. Adipocytes (fat cells) produce at least 50 proteins (adipokines; peptides, cytokines, etc.), and a large part of them are involved in prenatal development of insulin resistance. The role of pro-inflammatory cytokines as the tumor necrosis factor 1 (TNF alpha), interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) is documented. Leptin from adipocytes as well as from the placenta is involved in pathology of metabolism and plays a role as a gestational factor for the prenatal insulin resistance and the risk for T2DM. Epigenetic mechanisms as the methylation of DNA and histones, the acetylation of histones are documented for prenatal development of insulin resistance. Epigenetic modulations may explain the risk of T2DM for generations. New data indicated that the placenta does not produce adiponectin and it is also one of the important factors for the development of gestational diabetes and risk for the fetus. Taken together all factors documented in the present paper may predict the risk for prenatal T2DM. PMID:25558670

  1. Dietary glycemic index, glycemic load, fiber, simple sugars, and insulin resistance - The Inter99 study

    Lau, Cathrine; Pedersen, Oluf; Færch, Kristine;

    2005-01-01

    OBJECTIVE - 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. RESEARCH DESIGN AND METHODS - The inter99 study is a nonpharmacolo......OBJECTIVE - 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. RESEARCH DESIGN AND METHODS - The inter99 study...... is a nonpharmacological intervention study. We used baseline data and examined cross-sectional associations between carbohydrate-related dietary factors and an estimate of insulin resistance in 5,675 subjects at 30 - 60 years. The dietary intake was estimated from a self-administered food frequency questionnaire......, and insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Multiple regressions were performed with HOMA-IR as the dependent variable and carbohydrate-related factors as explanatory variables. All models were adjusted for age, sex, smoking, physical activity...

  2. A better parameter in predicting insulin resistance: Obesity plus elevated alanine aminotransferase

    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.

  3. Association Between Chilli Food Habits with Iron Status and Insulin Resistance in a Chinese Population

    Li, Jiang; Wang, Rui; Xiao, Cheng

    2014-01-01

    Some studies have indicated that the consumption of chilli-containing foods can influence iron absorption and affect serum insulin and glucose concentrations, which may help to alleviate diabetes or prediabetes. The objective of this study was to explore the relationship between chilli food habits with iron status and insulin resistance in the Chinese population. Fasting blood samples, anthropometric data, and chilli food habit data collected from 8433 adults (aged 18 to 99), in 2009, as part...

  4. The passive coping Roman Low Avoidance rat, a non-obese rat model for insulin resistance

    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 ...

  5. Myeloperoxidase Deletion Prevents High-Fat Diet–Induced Obesity and Insulin Resistance

    Wang, Qilong; Xie, Zhonglin; Zhang, Wencheng; Zhou, Jun; Wu, Yue; Zhang, Miao; Zhu, Huaiping; Zou, Ming-Hui

    2014-01-01

    Activation of myeloperoxidase (MPO), a heme protein primarily expressed in granules of neutrophils, is associated with the development of obesity. However, whether MPO mediates high-fat diet (HFD)-induced obesity and obesity-associated insulin resistance remains to be determined. Here, we found that consumption of an HFD resulted in neutrophil infiltration and enhanced MPO expression and activity in epididymal white adipose tissue, with an increase in body weight gain and impaired insulin sig...

  6. Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats

    Park, Jeong-Kwon; Kim, Sang-Pyo; Song, Dae-Kyu

    2008-01-01

    OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium (KATP) channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity i...

  7. PTPRT Regulates High-Fat Diet-Induced Obesity and Insulin Resistance

    Feng, Xiujing; Scott, Anthony; Wang, Yong; Wang, Lan; Zhao, Yiqing; Doerner, Stephanie; Satake, Masanobu; Croniger, Colleen M.; Wang, Zhenghe

    2014-01-01

    Obesity is a risk factor for many human diseases. However, the underlying molecular causes of obesity are not well understood. Here, we report that protein tyrosine phosphatase receptor T (PTPRT) knockout mice are resistant to high-fat diet-induced obesity. Those mice avoid many deleterious side effects of high-fat diet-induced obesity, displaying improved peripheral insulin sensitivity, lower blood glucose and insulin levels. Compared to wild type littermates, PTPRT knockout mice show reduce...

  8. Quercetin improves insulin resistance and hepatic lipid accumulation in vitro in a NAFLD cell model

    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...

  9. Impaired Translocation of GLUT4 Results in Insulin Resistance of Atrophic Soleus Muscle

    Peng-Tao Xu; Zhen Song; Wen-Cheng Zhang; Bo Jiao; Zhi-Bin Yu

    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 sole...

  10. Insulin resistance improves metabolic and contractile efficiency in stressed rat heart

    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...

  11. The Relationship between Serum Ferritin and Insulin Resistance in Different Glucose Metabolism in Nonobese Han Adults

    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...

  12. Impaired Mitochondrial Function and Insulin Resistance of Skeletal Muscle in Mitochondrial Diabetes

    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...

  13. Insulin resistance and its relation to inflammatory status and serum lipids among young women with PCOS

    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...

  14. Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults

    Solomon, Thomas; Sistrun, Sakita N; Krishnan, Raj K;

    2008-01-01

    training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake...... fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P

  15. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome

    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 ...

  16. Association of adiponectin gene polymorphism with adiponectin levels and risk for insulin resistance syndrome

    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...

  17. Fat Distribution and Insulin Resistance in Young Adult Nonobese Asian Indian Women

    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...

  18. Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates

    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) ...

  19. Relationship of hypovitaminosis d and insulin resistance in patients with coronary heart disease and metabolic syndrome

    Orlovsky, V. F.; Hordina, M. A.

    2013-01-01

    BACKGROUND: Insulin resistance (IR) - is one of the predictors of cardiovascular disease and progression of atherosclerosis, regardless of major classical risk factors. IR has become a global epidemic. Experimental data indicate that low concentration of vitamin D associated with IR, diabetes mellitus type 2, by reducing the sensitivity of peripheral tissues to insulin and dysfunction of β-pancreatic cells. Randomized studies showed that vitamin D supplements have a preventive role in the dev...

  20. Evaluation of neck circumference as a predictor of central obesity and insulin resistance in Chinese adults

    Wang, Xuhong; Zhang, Ning; Yu, Caiguo; Ji, Zhili

    2015-01-01

    Objectives: To evaluate whether neck circumference (NC) could be used as a valid and effective method for identifying obesity and insulin resistance (IR) in Chinese adults. Methods: A total of 3307 adults aged 20-65 years were randomly recruited from two communities of Tongzhou, Beijing. Height, weight, waist circumference (WC), hip circumference (HC), neck circumference (NC), blood pressure, fasting plasma glucose (FPG), fasting serum insulin (FINS), total cholesterol (TC), serum triglycerid...

  1. Relationships between acylated ghrelin with growth hormone, insulin resistance, lipid profile, and cardio respiratory function in lean and obese men

    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.

  2. Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats.

    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

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

    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.

  4. Vitamin D Deficiency in Obese Children and Its Relationship to Insulin Resistance and Adipokines

    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.

  5. Association between insulin resistance and c-reactive protein among Peruvian adults

    Gelaye Bizu

    2010-05-01

    Full Text Available Abstract Objective Insulin resistance (IR, a reduced physiological response of peripheral tissues to the action of insulin, is one of the major causes of type 2 diabetes. We sought to evaluate the relationship between serum C-reactive protein (CRP, a marker of systemic inflammation, and prevalence of IR among Peruvian adults. Methods This population based study of 1,525 individuals (569 men and 956 women; mean age 39 years old was conducted among residents in Lima and Callao, Peru. Fasting plasma glucose, insulin, and CRP concentrations were measured using standard approaches. Insulin resistance was assessed using the homeostasis model (HOMA-IR. Categories of CRP were defined by the following tertiles: 2.53 mg/l. Logistic regression procedures were employed to estimate odds ratios (OR and 95% confidence intervals (CI. Results Elevated CRP were significantly associated with increased mean fasting insulin and mean HOMA-IR concentrations (p 2.53 mg/l (upper tertile had a 2.18-fold increased risk of IR (OR = 2.18 95% CI 1.51-3.16 as compared with those in the lowest tertile ( Conclusion Our observations among Peruvians suggest that chronic systemic inflammation, as evidenced by elevated CRP, may be of etiologic importance in insulin resistance and diabetes.

  6. Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose- fed rat

    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...

  7. Akt and Rac1 signalling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance

    Sylow, Lykke; Kleinert, Maximilian; Pehmøller, Christian; Prats Gavalda, Clara; Chiu, Tim T; Klip, Amira; Richter, Erik; Jensen, Thomas Elbenhardt

    2014-01-01

    pathways signal to increase glucose transport independently of each other and are simultaneously downregulated in insulin resistant muscle. Pharmacological inhibition of Rac1 and Akt signalling was used to determine the contribution of each pathway to insulin-stimulated glucose uptake in mouse muscles. The...

  8. Trigonella foenum-graecum water extract improves insulin sensitivity and stimulates PPAR and γ gene expression in high fructose-fed insulin-resistant rats

    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.

  9. Sirtuin3 Dysfunction Is the Key Determinant of Skeletal Muscle Insulin Resistance by Angiotensin II.

    Daniela Macconi

    Full Text Available Angiotensin II promotes insulin resistance. The mechanism underlying this abnormality, however, is still poorly defined. In a different setting, skeletal muscle metabolism and insulin signaling are regulated by Sirtuin3.Here, we investigate whether angiotensin II-induced insulin resistance in skeletal muscle is associated with Sirtuin3 dysregulation and whether pharmacological manipulation of Sirtuin3 confers protection.Parental and GLUT4-myc L6 rat skeletal muscle cells exposed to angiotensin II are used as in vitro models of insulin resistance. GLUT4 translocation, glucose uptake, intracellular molecular signals such as mitochondrial reactive oxygen species, Sirtuin3 protein expression and activity, along with its downstream targets and upstream regulators, are analyzed both in the absence and presence of acetyl-L-carnitine. The role of Sirtuin3 in GLUT4 translocation and intracellular molecular signaling is also studied in Sirtuin3-silenced as well as over-expressing cells.Angiotensin II promotes insulin resistance in skeletal muscle cells via mitochondrial oxidative stress, resulting in a two-fold increase in superoxide generation. In this context, reactive oxygen species open the mitochondrial permeability transition pore and significantly lower Sirtuin3 levels and activity impairing the cell antioxidant defense. Angiotensin II-induced Sirtuin3 dysfunction leads to the impairment of AMP-activated protein kinase/nicotinamide phosphoribosyltransferase signaling. Acetyl-L-carnitine, by lowering angiotensin II-induced mitochondrial superoxide formation, prevents Sirtuin3 dysfunction. This phenomenon implies the restoration of manganese superoxide dismutase antioxidant activity and AMP-activated protein kinase activation. Acetyl-L-carnitine protection is abrogated by specific Sirtuin3 siRNA.Our data demonstrate that angiotensin II-induced insulin resistance fosters mitochondrial superoxide generation, in turn leading to Sirtuin3 dysfunction. The

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

    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

  11. Dietary glycemic index, glycemic load, fiber, simple sugars, and insulin resistance - The Inter99 study

    Lau, Cathrine; Pedersen, Oluf; Færch, Kristine; Carstensen, Bendix; Glumer, Charlotte; Jørgensen, Torben; Tetens, Inge; Borch-Johnsen, Knut

    2005-01-01

    high glycemic load or diets with a high content of total carbohydrate including simple sugars was not associated with the probability of having insulin resistance. Furthermore, intake of dietary fiber was inversely associated with the probability of having insulin resistance.......OBJECTIVE - 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. RESEARCH DESIGN AND METHODS - The inter99 study is a.......05). Intake of dietary fiber explained the associations with daily glycemic load and total carbohydrate and attenuated the association with fruit and vegetables. No significant associations were observed for daily glycemic index or sucrose. CONCLUSIONS - Habitual intake of diets with a high glycemic index and...

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

    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. Autophagy: A Potential Link between Obesity and Insulin Resistance

    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

  14. Persistent Organic Pollutants and Concern Over the Link with Insulin Resistance Related Metabolic Diseases.

    Mostafalou, Sara

    2016-01-01

    Persistent organic pollutants (POPs) are mostly halogenated compounds tending to persist in the environment, enter into the food chain, and accumulate in fat mass of mammals due to their high lipophilicity. They include some organochlorine pesticides, polychlorinated biphenyls, brominated flame retardants and polycyclic aromatic hydrocarbons. Some of these chemicals were widely used in the past so that their residues can be detected in the human body, though their usage has been banned for years. POPs have been shown to perturb the health of biological systems in different ways evidenced by carcinogenicity and disrupting effects on endocrine, immune, and reproductive systems. There are many epidemiologic and experimental studies on the association of exposure to POPs with insulin resistance and related metabolic disorders like obesity, diabetes, and metabolic syndrome. Inflammation as a known mechanism accompanying insulin resistance has also been shown to arise in insulin target tissues exposed to POPs. This review addresses the breast milk concentration of POPs in different regions of the world, synthesizes the current information on the association of POPs with insulin resistance related metabolic disorders, and discusses the inflammation as an involved mechanism. Considering high prevalence of insulin resistance related metabolic diseases and their relation with POPs, much need is felt regarding international and regional programs to not only limit their production and usage but eliminate these persistent pollutants from the environment. PMID:26670033

  15. Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats.

    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

  16. Urine C-peptide creatinine ratio can be used to assess insulin resistance and insulin production in people without diabetes: an observational study

    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...

  17. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

    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. Evaluation of organ-specific glucose metabolism by 18F-FDG in insulin receptor substrate-1 (IRS-1) knockout mice as a model of insulin resistance

    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

  19. Skeletal muscle mitochondrial bioenergetics and morphology in high fat diet induced obesity and insulin resistance: focus on dietary fat source

    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.

  20. Association of acanthosis nigricans and skin tags with insulin resistance Associação de acantose nigricante e acrocórdons à resistência insulínica

    Mariana Tremel Barbato; Paulo Ricardo Criado; Ana Kris da Silva; Evelyne Averbeck; Marina Bensen Guerine; Naiana Bittencourt de Sá

    2012-01-01

    Insulin resistance is a metabolic disorder in which target cells fail to respond to normal levels of circulating insulin. Insulin resistance has been associated with presence of acanthosis nigricans and acrochordons. It is known that early diagnosis and early initial treatment are of paramount importance to prevent a series of future complications. These dermatoses may represent an easily identifiable sign of insulin resistance and non-insulin-dependent diabetes.A resistência insulínica é uma...