scholarly journals Heterozygous knockout of the IRS-1 gene in mice enhances obesity-linked insulin resistance: a possible model for the development of type 2 diabetes

2002 ◽  
Vol 174 (2) ◽  
pp. 309-319 ◽  
Author(s):  
A Shirakami ◽  
T Toyonaga ◽  
K Tsuruzoe ◽  
T Shirotani ◽  
K Matsumoto ◽  
...  

Insulin receptor substrate 1 (IRS-1) gene polymorphisms have been identified in type 2 diabetic patients; however, it is unclear how such polymorphisms contribute to the development of diabetes. Here we introduced obesity in heterozygous IRS-1 knockout (IRS-1(+/-)) mice by gold-thioglucose (GTG) injection and studied the impact of reduced IRS-1 expression on obesity-linked insulin resistance. GTG injection resulted in approximately 30% weight gain in IRS-1(+/-) and wild type (WT) mice, compared with saline-injected controls. There was no difference in insulin sensitivity between lean IRS-1(+/-) and lean WT. Elevated fasting insulin levels but no change in fasting glucose were noted in obese IRS-1(+/-) and WT compared with the respective lean controls. Importantly, fasting insulin in obese IRS-1(+/-) was 1.5-fold higher (P<0.05) than in obese WT, and an insulin tolerance test showed a profound insulin resistance in obese IRS-1(+/-) compared with obese WT. The islets of obese IRS-1(+/-) were 1.4-fold larger than those of obese WT. The expression of insulin receptor and IRS-1 and IRS-2 was decreased in obese IRS-1(+/-), which could in part explain the profound insulin resistance in these mice. Our results suggest that IRS-1 is the suspected gene for type 2 diabetes and its polymorphisms could worsen insulin resistance in the presence of other additional factors, such as obesity.

2018 ◽  
Vol 13 (1) ◽  
pp. 155798831880704
Author(s):  
Moustafa A. Elsaied ◽  
Doaa Masallat ◽  
Ibrahim A. Abdel-Hamid

The aim of this study was to evaluate the levels of adiponectin in diabetic patients with and without erectile dysfunction (ED). In addition, the correlations of adiponectin with the scores of international index of erectile function (IIEF) and total testosterone levels were explored in diabetic and nondiabetic patients with ED. The study included three groups: Type 2 Diabetic patients (T2DM) with and without ED and a third nondiabetics with ED group, each of 29 patients. Fasting blood glucose (FBG), fasting insulin (FI), homeostasis model assessments of insulin resistance (HOMA-IR index), testosterone and adiponectin levels were evaluated. IIEF was applied to diabetic and nondiabetic patients with ED. The results showed that adiponectin was lower in diabetic patients with ED than in both nondiabetics with ED and diabetics without ED groups (5.23 ± 1.05 vs. 11.38 ± 10.08 and 6.5 ± 2.13; p = .003 and .006 respectively). Testosterone was lower in diabetic patients with ED than in diabetics without ED group (2.52 ± 1.15 vs. 4.1 ± 1.46; p = .024). Testosterone had a direct correlation with adiponectin ( r = .371; p = .001). Both adiponectin and testosterone levels did not correlate with IIEF. In conclusion, the decreased adiponectin and testosterone are associated with ED in T2DM. Testosterone has a direct correlation with circulating adiponectin while both have no correlation with IIEF.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A413-A414
Author(s):  
Mala Dharmalingam ◽  
Ganavi Pattabhi

Abstract Fetuin-A has been implicated in the causation of metabolic disorders such as obesity, diabetes, and hepatic steatosis. There are numerous studies which have shown the association between levels of fetuin-A in Type 2 diabetes mellitus (T2DM) and Nonalcoholic fatty liver disease (NAFLD). The levels of fetuin-A in newly detected type 2 diabetic patients (NDD) and its correlation with presence of NAFLD has not been studied. Objective: To study the fetuin-A levels in patients with NDD and its correlation with NAFLD. Methods: A total of 60 newly diagnosed type 2 diabetes (NDD) were studied. Diagnosis of NAFLD was made on the basis of transient elastography. Serum fetuin-A and serum fasting insulin were measured along with other investigations. Results: Percentage of patients with NAFLD in NDD was 53.33%. Fetuin-A levels were significantly higher in NDD with NAFLD compared to those without NAFLD. There was no association of fetuin-A with age, both systolic and diastolic blood pressure, FBS, HbA1c, fasting insulin, HOMA-IR, QUICKI and markers of advanced fibrosis. Fetuin-A levels beyond 1166.5 mcg/ml could predict the development of NAFLD with OR of 4.33 (95%CI:1.364–13.77) which remained significant after adjustment for various confounding factors. Conclusion: Fetuin-A is a reliable marker of NAFLD in NDD and is positively associated with IR. The observation in this study suggests that high serum fetuin-A levels in patients with NAFLD do not merely reflect the effects of insulin resistance, but also a more extensive distortion of liver architecture.


Author(s):  
Anil B. Choudhury ◽  
Shankar M. Pawar ◽  
Purnima Dey Sarkar ◽  
Keerti Gopi

Background: Accumulating evidence suggests that adiponectin, a major adipocyte secretory protein, has insulin-sensitizing and anti-atherogenic properties and protects against later development of type 2 diabetes. We investigated the association of adiponectin with insulin resistance, blood lipids and type 2 diabetes in non obese central Indian population.Methods: Anthropometric and biochemical parameters were measured in 149 (81 male and 68 female) newly diagnosed non obese type 2 diabetic patients and 157 (85 male and 72 female) age and body mass index (BMI) matched controls.Results: Adiponectin level (p<0.0001) was significantly lower in the diabetic group than in non diabetic control. In an age, gender and BMI adjusted model, adiponectin level was significantly negatively correlated with waist circumference, waist to hip ratio, systolic blood pressure, fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) (p= 0.0034), HbA1C, total cholesterol, LDL-cholesterol, and triglycerides (p<0.0001) and positively correlated with HDL-cholesterol (p =0.0014) in non obese type 2 diabetic group. However, there was no significant correlation between adiponectin and glucose in this study. In stepwise linear regression analysis, adjusted for potential confounder, significant inverse association was observed between serum adiponectin level and HOMA-IR (p = 0.0001). In multivariate logistic regression model, adjusted for age, gender, BMI, waist circumference, and waist-hip ratio, lower adiponectin was independently associated with the presence of type 2 diabetes (p<0.0001).Conclusions: Lower adiponectin levels in non obese type 2 diabetic patients were significantly related to the increased insulin resistance, dyslipidemia, and presence of type 2 diabetes, independently of overall and abdominal adiposity, thereby suggesting a direct link between adiponectin and carbohydrate and lipid metabolism in human.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Chung-Hua Hsu

Objective.To examine the different impacts of MS components on insulin resistance in type 2 diabetes.Methods.A number of subjects (144) who met the criteria of (1) age between 30 and 75 years, (2) had type 2 diabetes for more than one year, and (3) taking gliclazide and metformin for more than 6 months were enrolled. All subjects were assigned to one of the four HOMA index categories. The HOMA index quartile 4 denotes the highest insulin resistance. The main outcome evaluated is the odds ratios (ORs) of different MS components on HOMA index quartile 4. The characteristics in HOMA index quartiles and groups of nonmetabolic syndrome (NMS; number of components < 2), metabolic syndrome A (MSA; number of components = 2), and metabolic syndrome B (MSB; number of components > 2) were also evaluated.Results.The results showed that both MSA and MSB groups had higher ORs (5.9 and 13.8 times, resp.) than the NMS group; and that subjects with large waist circumference (LWC) and high triglyceride (HTG) level have higher ORs (6.1 and 2.6 times, resp.) in developing higher insulin resistance than normal control subjects.Conclusion.Type 2 diabetic patients with greater number of MS components have higher ORs in developing increased insulin resistance.


2016 ◽  
Vol 31 (1) ◽  
pp. 108-114 ◽  
Author(s):  
Ahmad Zare Javid ◽  
Razie Hormoznejad ◽  
Hojat allah Yousefimanesh ◽  
Mehrnoosh Zakerkish ◽  
Mohammad Hosein Haghighi-zadeh ◽  
...  

2013 ◽  
Vol 154 (44) ◽  
pp. 1747-1753
Author(s):  
Györgyi Kovács ◽  
Barbara Buday ◽  
Attila Fék ◽  
Botond Literáti-Nagy ◽  
József Pauer ◽  
...  

Introduction: Today the prevalence of type 2 diabetes reached an epidemic level. It is known that type 2 diabetes could only be prevented before the manifestation, during the “prediabetic” state, urging the development of diagnostic tests to recognize the group at risk in time. Aim: The authors explored metabolic differences between healthy, normal glucose tolerant, normal insulin resistant females having first degree relatives with and without type 2 diabetes. Method: Healthy, normal insulin sensitive females without (n = 26) and with (n = 18) type 2 diabetic relatives were investigated. Results: Healthy females with first degree diabetic relatives had lower low density lipoproteins and higher high density lipoproteins as well as higher glucose and insulin levels at the 120 min of oral glucose test as compared to those without first degree diabetic relatives. Conclusions: These results suggest that the appearance of insulin resistance is preceded by hepatic insulin resistance and impaired lipid metabolism in the symptom-free prediabetic period of genetically suceptible females. Orv. Hetil., 154 (44), 1747–1753.


2018 ◽  
Vol 15 (1) ◽  
pp. 62-66 ◽  
Author(s):  
Armin Mahdiani ◽  
Masoume Kheirandish ◽  
Shokoufeh Bonakdaran

Background: The role of chronic inflammation in insulin resistance states and the pathogenesis of metabolic syndrome, cardiovascular disease and diabetes have been reported earlier. White Blood Cell (WBC) count is an easy marker for estimation of systemic inflammation. Objective: This study is to clarify whether WBC count is associated with insulin resistance in type 2 diabetic patients. Methods: This cross sectional study was conducted in 283 patients with type 2 diabetes and in 283 healthy non diabetic subjects as control group. Data including: age, gender, blood pressure, height and weight, history of smoking were collected for each patient. Fasting blood sugar, HbA1C, insulin, lipid profiles, creatinine, Urine albumin to creatinine ratio, high sensitive C- reactive protein (HCRP) and WBC was measured for all patients. WBC count was measured in control group. Two groups were compared in WBC count. Insulin resistance was calculated with HOMA-IR formula. Association of WBC count with insulin resistance and metabolic parameters was assessed in diabetic patients. Results: WBC count was significantly associated with body mass index, hypertension, and triglyceride level. There was not significant association between WBC count and glycemic index and insulin resistance. Conclusion: An elevated WBC count (even in the normal range) is closely related to various components of metabolic syndrome but not related to insulin resistance in type 2 diabetes.


Author(s):  
Alaa H. Jawad ◽  
Ammal E. Ibrahim ◽  
Raghda Alsayed ◽  
Zainab Salih Hallab ◽  
Zyad Al-Qaisi ◽  
...  

Glucose-6-phosphatase (G6Pase), an enzyme found mostly in the kidneys and the liver, acting significant role of supplying glucose through starvation. This study includes (84) subjects, their age ranged from (40 to 54) years. (20) subjects were healthy chosen as control group and (64) patients with type 2 diabetes mellitus were divided into three groups according to their type of anti diabetic therapy : (23) newly diagnosed group without therapy (Group1), (20) with metformin therapy (Group2) and (21) with metformin plus glibenclamide therapies( Group3). The study found that G-6-Pase activity is increased, thereby leading to an increase in endogenous glucose production (EGP) in patients with type 2 diabetes and, therefore FPG will increase. The result found that increasing G-6-Pase activity will increase the concentration of glucose in the blood and that will increase the long-term glycemic control (HbA1c%).


2004 ◽  
pp. 573-577 ◽  
Author(s):  
A Katsuki ◽  
H Urakawa ◽  
EC Gabazza ◽  
S Murashima ◽  
K Nakatani ◽  
...  

OBJECTIVE: To investigate the relationship between the circulating level of active ghrelin and abdominal adiposity, serum levels of insulin or insulin resistance in patients with type 2 diabetes mellitus. DESIGN: We measured the plasma levels of the active form of ghrelin in 18 obese and 18 nonobese patients with type 2 diabetes mellitus using a radioimmunoassay (RIA) kit. Body fat accumulation was measured by computed tomography (CT) and insulin resistance by the glucose infusion rate (GIR) during an euglycemic hyperinsulinemic clamp study. RESULTS: Plasma levels of ghrelin in obese patients with type 2 diabetes mellitus were significantly decreased compared with nonobese patients. There were significant correlations between the plasma levels of ghrelin and BMI (r=-0.505, P<0.01), visceral (r=-0.444, P<0.01), subcutaneous (r=-0.506, P<0.01) and total (r=-0.534, P<0.01) fat area, serum levels of insulin (r=-0.513, P<0.01) or GIR (r=0.478, P<0.01) in type 2 diabetic patients. The plasma level of ghrelin was significantly associated with serum levels of insulin (F=8.468, P<0.05) or GIR (F=8.522, P<0.05) after adjustment for BMI in patients with type 2 diabetes mellitus. CONCLUSIONS: Decreased plasma levels of active ghrelin are significantly associated with abdominal adiposity, hyperinsulinemia and insulin resistance in type 2 diabetic patients. Hyperinsulinemia associated with insulin resistance may suppress plasma levels of active ghrelin in patients with type 2 diabetes mellitus.


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