scholarly journals Adipose Tissue, Muscle, and Function: Potential Mediators of Associations Between Body Weight and Mortality in Older Adults With Type 2 Diabetes

Diabetes Care ◽  
2014 ◽  
Vol 37 (12) ◽  
pp. 3213-3219 ◽  
Author(s):  
Rachel A. Murphy ◽  
Ilse Reinders ◽  
Melissa E. Garcia ◽  
Gudny Eiriksdottir ◽  
Lenore J. Launer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Body Weight ◽  
Adipose Tissue ◽  
And Function ◽  
Function Potential

scholarly journals Insulin and Insulin Receptors in Adipose Tissue Development

2019 ◽  
Vol 20 (3) ◽  
pp. 759 ◽  
Author(s):  
Angelo Cignarelli ◽  
Valentina Genchi ◽  
Sebastio Perrini ◽  
Annalisa Natalicchio ◽  
Luigi Laviola ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Intracellular Signaling ◽  
Insulin Receptors ◽  
Metabolic Effects ◽  
Endocrine Activity ◽  
Differentiated Cells ◽  
And Function

Insulin is a major endocrine hormone also involved in the regulation of energy and lipid metabolism via the activation of an intracellular signaling cascade involving the insulin receptor (INSR), insulin receptor substrate (IRS) proteins, phosphoinositol 3-kinase (PI3K) and protein kinase B (AKT). Specifically, insulin regulates several aspects of the development and function of adipose tissue and stimulates the differentiation program of adipose cells. Insulin can activate its responses in adipose tissue through two INSR splicing variants: INSR-A, which is predominantly expressed in mesenchymal and less-differentiated cells and mainly linked to cell proliferation, and INSR-B, which is more expressed in terminally differentiated cells and coupled to metabolic effects. Recent findings have revealed that different distributions of INSR and an altered INSR-A:INSR-B ratio may contribute to metabolic abnormalities during the onset of insulin resistance and the progression to type 2 diabetes. In this review, we discuss the role of insulin and the INSR in the development and endocrine activity of adipose tissue and the pharmacological implications for the management of obesity and type 2 diabetes.

Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats

2017 ◽  
Vol 42 (2) ◽  
pp. 181-192 ◽  
Author(s):  
Mohamed M. Amin ◽  
Mahmoud S. Arbid
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Signaling ◽  
Inflammatory Mediators ◽  
Ellagic Acid ◽  
Molecular Mechanisms ◽  
Combined Treatment ◽  
Albino Rats

Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.

scholarly journals Huntingtin-associated protein 1 plays an essential role in the pathogenesis of type 2 diabetes by regulating the translocation of GLUT4 in mouse adipocytes

2020 ◽  
Vol 8 (1) ◽  
pp. e001199
Author(s):  
Yan-Ju Gong ◽  
Ying Feng ◽  
Yuan-Yuan Cao ◽  
Jia Zhao ◽  
Wei Wu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
Hek293 Cells ◽  
Diabetic Mice ◽  
Glut4 Translocation ◽  
Mouse Adipocytes

ObjectiveGlucose disposal by insulin-responsive tissues maintains the body glucose homeostasis and insulin resistance leads to a risk of developing type 2 diabetes (T2DM). Insulin stimulates the translocation of glucose transporter isoform 4 (GLUT4) vesicles from intracellular compartments to the plasma membrane to facilitate glucose uptake. However, the underlying mechanisms of GLUT4 vesicle translocation are not well defined. Here we show the role of huntingtin-associated protein 1 (HAP1) in GLUT4 translocation in adipocytes and the pathogenesis of T2DM.Research design and methodsThe parameters for glucose metabolism including body weight, glucose tolerance and insulin tolerance were assessed in wild-type (WT) and Hap1+/- mice. HAP1 protein expression was verified in adipose tissue. Hap1 mRNA and protein expression was monitored in adipose tissue of high-fat diet (HFD)-induced diabetic mice. Insulin-stimulated GLUT4 vesicle translocation and glucose uptake were detected using immunofluorescence techniques and quantified in primary adipocytes from Hap1-/- mice. The interaction between HAP1 and GLUT4 was assessed by immunofluorescence colocalization and co-immunoprecipitation in HEK293 cells and adipose tissue. The role of sortilin in HAP1 and GLUT4 interaction was approved by co-immunoprecipitation and RNA interference.ResultsThe expression of Hap1 mRNA and protein was detected in WT mouse adipose tissue and downregulated in adipose tissue of HFD-induced diabetic mice. Hap1+/- mice exhibited increased body weight, pronounced glucose tolerance and significant insulin intolerance compared with the WT mice. HAP1 colocalized with GLUT4 in mouse adipocytes and cotransfected HEK293 cells. Furthermore, the insulin-stimulated GLUT4 vesicle translocation and glucose uptake were defective in Hap1-/- adipocytes. Finally, sortilin mediated the interaction of HAP1 and GLUT4.ConclusionsOur study showed that HAP1 formed a protein complex with GLUT4 and sortilin, and played a critical role in insulin-stimulated GLUT4 translocation in adipocytes. Its downregulation may contribute to the pathogenesis of diabetes.

scholarly journals Social Isolation Affects the Development of Obesity and Type 2 Diabetes in Mice

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4658-4666 ◽  
Author(s):  
Katsunori Nonogaki ◽  
Kana Nozue ◽  
Yoshitomo Oka
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Social Isolation ◽  
Food Consumption ◽  
Leptin Receptor ◽  
Body Weight Gain ◽  
Kkay Mice

Social isolation is associated with increased risks of mortality and morbidity. In this study, we show that chronic individual housing accelerated body weight gain and adiposity in KK mice but not C57BL6J mice, and fully developed diabetes in KKAy mice. Individually housed KK and KKAy mice increased body weight gain over the initial 2 wk without increased daily average food consumption compared with group-housed animals. The individually housed KK and KKAy mice then gradually increased food consumption for the next 1 wk. The chronic social isolation-induced obesity (SIO) was associated with hyperleptinemia and lower plasma corticosterone and active ghrelin levels but not hyperinsulinemia. Elevated plasma leptin in the SIO suppressed expression of 5-HT2C receptor in white adipose tissue. The SIO was also associated with decreased expression of β3-adrenergic receptors in white adipose tissue and hypothalamic leptin receptor, which might be secondary to the enhanced adiposity. Interestingly, social isolation acutely reduced food consumption and body weight gain compared with group-housed obese db/db mice with leptin receptor deficiency. Social isolation-induced hyperglycemia in KKAy mice was associated with increased expression of hepatic gluconeogenetic genes independent of insulin. These findings suggest that social isolation promotes obesity due to primary decreased energy expenditure and secondary increased food consumption, which are independent of the disturbed leptin signaling, in KK mice, and develops into insulin-independent diabetes associated with increased expression of hepatic gluconeogenetic genes in KKAy mice. Thus, social isolation can be included in the environmental factors that contribute to the development of obesity and type 2 diabetes.

scholarly journals Muscle and adipose tissue biopsy in older adults with type 2 diabetes

2011 ◽  
Vol 01 (03) ◽  
pp. 27-35 ◽  
Author(s):  
Yi Wang ◽  
David Simar ◽  
Kylie Anderberg ◽  
Yorgi Mavros ◽  
Shelley Kay ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Adipose Tissue ◽  
Tissue Biopsy

scholarly journals Small-Molecule Insulin Mimetic Reduces Hyperglycemia and Obesity in a Nongenetic Mouse Model of Type 2 Diabetes

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5259-5268 ◽  
Author(s):  
Mathias Z. Strowski ◽  
Zhihua Li ◽  
Deborah Szalkowski ◽  
Xiaolan Shen ◽  
Xiao-Ming Guan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Mouse Model ◽  
Small Molecule ◽  
White Adipose Tissue ◽  
Body Weight Gain ◽  
Nonesterified Fatty Acids

Abstract Adiposity positively correlates with insulin resistance and is a major risk factor of type 2 diabetes. Administration of exogenous insulin, which acts as an anabolic factor, facilitates adipogenesis. Recently nonpeptidal insulin receptor (IR) activators have been discovered. Here we evaluate the effects of the orally bioavailable small-molecule IR activator (Compound-2) on metabolic abnormalities associated with type 2 diabetes using a nongenetic mouse model in comparison with the effects of a novel non-thiazolidinedione (nTZD) peroxisome proliferator-activated receptor-γ agonist. Both Compound-2 and nTZD alleviated fasting and postprandial hyperglycemia; accelerated glucose clearance rate; and normalized plasma levels of nonesterified fatty acids, triglycerides, and leptin. Unlike nTZD, which increased body weight gain, and total fat mass, which is a common feature for PPARγ agonists, Compound-2 prevented body weight gain and hypertrophy of brown, and white adipose tissue depots and the development of hepatic steatosis in the mouse model of type 2 diabetes. The effect of the two compounds on proximal steps in insulin signal transduction pathway was analyzed in tissues. Compound-2 enhanced insulin-stimulated phosphorylation of IR tyrosine and/or Akt in the liver, skeletal muscle, and white adipose tissue, whereas nTZD potentiated the phosphorylation of IR and Akt in the adipose tissue only. In conclusion, small-molecule IR activators have unique features as insulin sensitizers and hold potential utility in the treatment of type 2 diabetes and obesity.

How to Maintain a Healthy Body Weight

2006 ◽  
Vol 76 (4) ◽  
pp. 208-215 ◽  
Author(s):  
Astrup
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Glycemic Index ◽  
Dairy Products ◽  
Weight Control ◽  
Healthy Body Weight ◽  
Healthy Body

The epidemic of both obesity and type 2 diabetes is due to environmental factors, but the individuals developing the conditions possess a strong genetic predisposition. Observational surveys and intervention studies have shown that excess body fatness is the major environmental cause of type 2 diabetes, and that even a minor weight loss can prevent its development in high-risk subjects. Maintenance of a healthy body weight in susceptible individuals requires 45–60 minutes physical activity daily, a fat-reduced diet with plenty of fruit, vegetables, whole grain, and lean meat and dairy products, and moderate consumption of calorie containing beverages. The use of table values to predict the glycemic index of meals is of little – if any – value, and the role of a low-glycemic index diet for body weight control is controversial. The replacement of starchy carbohydrates with protein from lean meat and lean dairy products enhances satiety, and facilitate weight control. It is possible that dairy calcium also promotes weight loss, although the mechanism of action remains unclear. A weight loss of 5–10% can be induced in almost all obese patients providing treatment is offered by a professional team consisting of a physician and dieticians or nurses trained to focus on weight loss and maintenance. Whereas increasing daily physical activity and regular exercise does not significantly effect the rate of weight loss in the induction phase, it plays an important role in the weight maintenance phase due to an impact on daily energy expenditure and also to a direct enhancement of insulin sensitivity.

Clinical Experience with Insulin Detemir: Results from the Bangladesh Cohort of Global A1chieve Study

2013 ◽  
Vol 3 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Zafar Ahmed Latif ◽  
Md. Faruque Pathan ◽  
Md. Nazrul Islam Siddiqui ◽  
MA Mannan ◽  
SM Ashrafuzzaman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Glycaemic Control ◽  
Insulin Therapy ◽  
Hba1c Level ◽  
Insulin Detemir ◽  
Entire Cohort ◽  
Baseline Visit ◽  
Effective Option

Objective: To present results from the Bangladesh cohort of the A1chieve study receiving insulin detemir (Levemir) ± oral anti diabetic drugs. Methods: Out of 1093 patients recruited from 49 sites in Bangladesh, 370 were initiated on insulin detemir (Levemir).Study visits were defined as baseline, interim (around 12 weeks from baseline) and final (around 24 weeks from baseline) visit. Results: Glycaemic control was poor in all the groups at baseline. In the entire cohort at 24 weeks, significant reductions from baseline were observed in mean HbA1c (from 10.0 % to 7.2%, p<0.001), FPG (from 10.5 to 6.7 mmol/L, p<0.001) and PPPG (from 15.3 to 8.9 mmol/L, p<0.001) levels. Overall 45.5% of the participants achieved target HbA1c level of < 7% after 24 weeks. The rate of all hypoglycaemic events in the entire cohort reduced from 1.34 (baseline) to 0.12 events/person year after 24 weeks of insulin detemir therapy (p<0.0001). There was no clinically relevant change in body weight in insulin naïve or prior insulin users groups after 24 weeks of insulin detemir therapy. Conclusions: The current study suggests that insulin detemir may be considered as a safe and effective option for initiating insulin therapy for type 2 diabetes in Bangladesh. Birdem Med J 2013; 3(1): 11-18 DOI: http://dx.doi.org/10.3329/birdem.v3i1.17121

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