scholarly journals Adipocytes Exhibit Abnormal Subcellular Distribution and Translocation of Vesicles Containing Glucose Transporter 4 and Insulin-Regulated Aminopeptidase in Type 2 Diabetes Mellitus: Implications Regarding Defects in Vesicle Trafficking

2001 ◽  
Vol 86 (11) ◽  
pp. 5450-5456 ◽  
Author(s):  
Lidia Maianu ◽  
Susanna R. Keller ◽  
W. Timothy Garvey
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Glucose Transporter ◽  
Diabetic Patients ◽  
Low Density ◽  
Glucose Transporter 4 ◽  
Glut 4

Insulin resistance in type 2 diabetes is due to impaired stimulation of the glucose transport system in muscle and fat. Different defects are operative in these two target tissues because glucose transporter 4 (GLUT 4) expression is normal in muscle but markedly reduced in fat. In muscle, GLUT 4 is redistributed to a dense membrane compartment, and insulin-mediated translocation to plasma membrane (PM) is impaired. Whether similar trafficking defects are operative in human fat is unknown. Therefore, we studied subcellular localization of GLUT4 and insulin-regulated aminopeptidase (IRAP; also referred to as vp165 or gp160), which is a constituent of GLUT4 vesicles and also translocates to PM in response to insulin. Subcutaneous fat was obtained from eight normoglycemic control subjects (body mass index, 29 ± 2 kg/m2) and eight type 2 diabetic patients (body mass index, 30 ± 1 kg/m2; fasting glucose, 14 ± 1 mm). In adipocytes isolated from diabetics, the basal 3-O-methylglucose transport rate was decreased by 50% compared with controls (7.1 ± 2.9 vs. 14.1 ± 3.7 mmol/mm2 surface area/min), and there was no increase in response to maximal insulin (7.9 ± 2.7 vs. 44.5 ± 9.2 in controls). In membrane subfractions from controls, insulin led to a marked increase of IRAP in the PM from 0.103 ± 0.04 to 1.00± 0.33 relative units/mg protein, concomitant with an 18% decrease in low-density microsomes and no change in high-density microsomes (HDM). In type 2 diabetes, IRAP overall expression in adipocytes was similar to that in controls; however, two abnormalities were observed. First, in basal cells, IRAP was redistributed away from low-density microsomes, and more IRAP was recovered in HDM (1.2-fold) and PM (4.4-fold) from diabetics compared with controls. Second, IRAP recruitment to PM by maximal insulin was markedly impaired. GLUT4 was depleted in all membrane subfractions (43–67%) in diabetes, and there was no increase in PM GLUT4 in response to insulin. Type 2 diabetes did not affect the fractionation of marker enzymes. We conclude that in human adipocytes: 1) IRAP is expressed and translocates to PM in response to insulin; 2) GLUT4 depletion involves all membrane subfractions in type 2 diabetes, although cellular levels of IRAP are normal; and 3) in type 2 diabetes, IRAP accumulates in membrane vesicles cofractionating with HDM and PM under basal conditions, and insulin-mediated recruitment to PM is impaired. Therefore, in type 2 diabetes, adipocytes express defects in trafficking of GLUT4/IRAP-containing vesicles similar to those causing insulin resistance in skeletal muscle.

scholarly journals Contribution of rs3211938 polymorphism at CD36 to glucose levels, oxidized low-density lipoproteins, insulin resistance, and body mass index in Mexican mestizos with type-2 diabetes from western Mexico

2021 ◽  
Author(s):  
Beatriz Teresita Martín-Márquez ◽  
Flavio Sandoval-Garcia ◽  
Mónica Vazquez-Del Mercado ◽  
Erika-Aurora Martínez-García ◽  
Fernanda-Isadora Corona-Meraz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Glucose Levels ◽  
Western Mexico ◽  
Mexican Mestizos

scholarly journals The effects of metformin plus sulfonylurea therapy on clinical features of the metabolic syndrome

2010 ◽  
Vol 63 (9-10) ◽  
pp. 611-615 ◽  
Author(s):  
Branka Koprivica ◽  
Teodora Beljic-Zivkovic ◽  
Tatjana Ille
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Glycemic Control ◽  
Body Mass ◽  
Combined Therapy

Introduction. Insulin resistance is a well-known leading factor in the development of metabolic syndrome. The aim of this study was to evaluate metabolic effects of metformin added to sulfonylurea in unsuccessfully treated type 2 diabetic patients with metabolic syndrome. Material and methods. A group of thirty subjects, with type 2 diabetes, secondary sulfonylurea failure and metabolic syndrome were administered the combined therapy of sulfonylurea plus metformin for six months. Metformin 2000 mg/d was added to previously used sulfonylurea agent in maximum daily dose. Antihypertensive and hypolipemic therapy was not changed. The following parameters were assessed at the beginning and after six months of therapy: glycemic control, body mass index, waist circumference, blood pressure, triglycerides, total cholesterol and its fractions, homeostatic models for evaluation of insulin resistance and secretion (HOMA R, HOMA B) and C- peptide. Results. Glycemic control was significantly improved after six months of the combined therapy: (fasting 7.89 vs. 10.61 mmol/l. p<0.01; postprandial 11.12 vs. 12.61 mmol/l. p<0.01, p<0.01; glycosylated hemoglobin 6.81 vs. 8.83%. p<0.01). the body mass index and waist circumference were significantly lower (26.7 vs. 27.8 kg/m2, p<0.01 and 99.7 vs. 101.4 cm for men, p<0.01; 87.2 vs. 88.5 for women, p<0.01). Fasting plasma triglycerides decreased from 3.37 to 2.45 mmol/l (p<0.001) and HOMA R from 7.04 to 5.23 (p<0.001). No treatment effects were observed on blood pressure, cholesterol, and residual insulin secretion. Conclusion. Administration of metformin in type 2 diabetes with metabolic syndrome decreased cardiovascular risk factors by reducing glycemia, triglycerides, BMI, central obesity and insulin resistance.

scholarly journals Body Mass Index: A Risk Factor for Retinopathy in Type 2 Diabetic Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Snježana Kaštelan ◽  
Martina Tomić ◽  
Antonela Gverović Antunica ◽  
Spomenka Ljubić ◽  
Jasminka Salopek Rabatić ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Developed Countries ◽  
Diabetes Duration ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Significant Deterioration ◽  
Group 2

The aim of the study was to investigate whether body mass index (BMI) independently or in correlation with other risk factors is associated with diabetic retinopathy (DR) progression. The study included 545 patients with type 2 diabetes. According to DR status, they were divided into three groups: group 1 (no retinopathy;n=296), group 2 (mild/moderate nonproliferative DR;n=118), and group 3 (severe/very severe NPDR or proliferative DR;n=131). Patients without DR were younger than those with signs of retinopathy at time of diabetes onset whilst diabetes duration was longer in groups with severe NPDR and PDR. DR progression was correlated with diabetes duration, BMI, HbA1c, hypertension, and cholesterol. Statistical analyses showed that the progression of retinopathy increased significantly with higher BMI (gr. 1: 26.50 ± 2.70, gr. 2: 28.11 ± 3.00, gr. 3: 28.69 ± 2.50;P<0.01). We observed a significant deterioration of HbA1c and a significant increase in cholesterol and hypertension with an increase in BMI. Correlation between BMI and triglycerides was not significant. Thus, BMI in correlation with HbA1c cholesterol and hypertension appears to be associated with the progression of DR in type 2 diabetes and may serve as a predictive factor for the development of this important cause of visual loss in developed countries.

scholarly journals The effect of combination therapy of insulin glargine, metformin, and sitagliptin on insulin secretion, insulin resistance, and metabolic parameters in obese subjects with type 2 diabetes

2016 ◽  
Vol 144 (9-10) ◽  
pp. 497-502
Author(s):  
Teodora Beljic-Zivkovic ◽  
Milica Marjanovic-Petkovic ◽  
Miljanka Vuksanovic ◽  
Ivan Soldatovic ◽  
Dobrila Kanlic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Insulin Glargine ◽  
Body Mass ◽  
Fasting Glucose ◽  
C Peptide ◽  
Obese Subjects

Introduction. A combination of drugs is required for treatment of obese subjects with diabetes, due to multiple pathogenic mechanisms implicated in the development of both diabetes and obesity. Objective. Assessment of the effect of sitagliptin added to insulin glargine and metformin, in obese subjects with type 2 diabetes. Methods. A total of 23 obese subjects on metformin and insulin glargine participated in the study. Titration of insulin glargine during a one-month period preceded the addition of 100 mg of sitagliptin daily. Body mass index, waist circumference, fasting, and prandial glucose were measured monthly, lipids and hemoglobin A1c (HbA1c) every three months, insulin, c-peptide and glucagon at the start and after six months of treatment. Homeostatic models for insulin secretion (HOMA B) and insulin resistance (HOMA IR) were calculated. Results. Participants were 58.65 ?} 7.62 years of age with a body mass index of 35.06 ?} 5.15 kg/m2, waist circumference of 115.04 ?} 15.5 cm, and the duration of diabetes of 4.11 ?} 2.57 years. With the titration of insulin glargine, target fasting glucose levels were not achieved. Waist circumference and body mass index decreased during three months of sitagliptin treatment, thereafter remaining stable. HbA1c decreased significantly after three and six months of therapy. C-peptide increased significantly, while glucagon level fell. HOMA indexes were unchanged. Conclusion. Sitagliptin can improve diabetes control and induce modest weight loss in obese subjects poorly controlled on insulin glargine and metformin. Titration of insulin glargine to optimal fasting glucose values is a prerequisite of success of this combination therapy.

Abstract P253: Body Mass Index and Heart Failure among Patients with Type 2 Diabetes

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Gang Hu ◽  
Peter Katzmarzyk ◽  
Ronald Horswell ◽  
Yujie Wang ◽  
Jolene Johnson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Reference Group ◽  
Smoking Status ◽  
Positive Association ◽  
University Hospital ◽  
Diabetic Patients

Background: Epidemiologic data on the association between body mass index (BMI) and heart failure (HF) risk among diabetic patients is rare. Aim: To investigate the association between BMI and HF risk among patients with type 2 diabetic in the Louisiana State University Hospital-based Longitudinal study (LSUHLS). Methods: We performed a prospective cohort study of risk for HF among 31,155 patients of type 2 diabetes (11,468 men and 19,687 women). Cox proportional hazards regression models were used to estimate the association of different levels of BMI with HF risk. Results: During a mean follow-up of 7.8 years, 5,834 subjects developed HF (2,379 men and 3,455 women). The multivariable-adjusted (age, race, smoking, income and type of insurance) hazard ratios of HF associated with BMI levels (18.5-22.9, 23-24.9, 25-29.9 [reference group], 30-34.9, 35-39.9, and ≥40 kg/m2) at baseline were 0.95, 1.00, 1.00, 1.16, 1.64, and 2.02 (Ptrend <0.001) for men, and 1.16, 1.16, 1.00, 1.23, 1.55, and 2.01 (Pnon-linear <0.001) for women, respectively. When we used an updated mean value of BMI, the association of HF risk with BMI did not change. When stratified by age, race, smoking status and use of anti-diabetic drugs, the positive association among men and the J-shaped association among women were still present. Conclusions: Our study suggests a positive association between BMI and HF risk among men, and a J-shaped association between BMI and HF risk among women with type 2 diabetes.

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