scholarly journals Cross-Talk between PPARγand Insulin Signaling and Modulation of Insulin Sensitivity

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-12 ◽  
Author(s):  
Anna Leonardini ◽  
Luigi Laviola ◽  
Sebastio Perrini ◽  
Annalisa Natalicchio ◽  
Francesco Giorgino
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Beneficial Effects ◽  
Major Mediator

PPARγactivation in type 2 diabetic patients results in a marked improvement in insulin and glucose parameters, resulting from an improvement of whole-body insulin sensitivity. Adipose tissue is the major mediator of PPARγaction on insulin sensitivity. PPARγactivation in mature adipocytes induces the expression of a number of genes involved in the insulin signaling cascade, thereby improving insulin sensitivity. PPARγis the master regulator of adipogenesis, thereby stimulating the production of small insulin-sensitive adipocytes. In addition to its importance in adipogenesis, PPARγplays an important role in regulating lipid, metabolism in mature adipocytes by increasing fatty acid trapping. Finally, adipose tissue produces several cytokines that regulate energy homeostasis, lipid and glucose metabolism. Disturbances in the production of these factors may contribute to metabolic abnormalities, and PPARγactivation is also associated with beneficial effects on expression and secretion of a whole range of cytokines.

Adiponectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients

2003 ◽  
Vol 284 (2) ◽  
pp. E443-E448 ◽  
Author(s):  
A. S. Lihn ◽  
T. Østergård ◽  
B. Nyholm ◽  
S. B. Pedersen ◽  
B. Richelsen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Subcutaneous Adipose Tissue ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Type 2 Diabetic Patients ◽  
Adiponectin Mrna ◽  
Subcutaneous Adipose ◽  
Type 2 Diabetic

Adiponectin is suggested to be an important mediator of insulin resistance. Therefore, we investigated the association between adiponectin and insulin sensitivity in 22 healthy first-degree relatives (FDR) to type 2 diabetic patients and 13 matched control subjects. Subcutaneous adipose tissue biopsies were taken before and after a hyperinsulinemic euglycemic clamp. FDR subjects were insulin resistant, as indicated by a reduced Mvalue (4.44 vs. 6.09 mg · kg−1· min−1, P < 0.05). Adiponectin mRNA expression was 45% lower in adipose tissue from FDR compared with controls ( P < 0.01), whereas serum adiponectin was similar in the two groups (6.4 vs. 6.6 μg/ml, not significant). Insulin infusion reduced circulating levels of adiponectin moderately (11–13%) but significantly in both groups ( P < 0.05). In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin ( P < 0.05) and positively correlated with insulin sensitivity ( P < 0.05). In contrast, these associations were not found in the FDR group. In conclusion, FDR have reduced adiponectin mRNA in subcutaneous adipose tissue but normal levels of circulating adiponectin. Adiponectin mRNA levels are positively correlated with insulin sensitivity in control subjects but not in FDR. These findings indicate dysregulation of adiponectin gene expression in FDR.

scholarly journals Exenatide with Metformin Ameliorated Visceral Adiposity and Insulin Resistance

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Xuan Du ◽  
Wen Lu ◽  
Zijun Lu ◽  
Xinyu Shao ◽  
Chunhong Hu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Low Income ◽  
Sequential Treatment ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Long Time ◽  
Total Adipose Tissue ◽  
Type 2 Diabetic

Background. To study the effectiveness of exenatide with metformin and sequential treatment with exenatide and glargine added to metformin and their influence on insulin sensitivity and adipose distribution. Methods. 20 newly diagnosed obese type 2 diabetic patients were enrolled, and 2-month washout treatment of metformin, 6-month exenatide treatment, and 6-month glargine treatment were administrated sequentially accompanied with previous metformin. Glucolipid metabolic parameters were compared among groups. Adipose distribution was quantified with computerized tomography according to anatomy, dividing into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), adding up to total adipose tissue (TAT). Results. The 6-month exenatide treatment dramatically ameliorated the glucose and lipid profile, improved insulin sensitivity, and mainly decreased VAT and also the ratio of VAT/SAT (RVS). The following 6-month glargine treatment increased VAT. The whole 12-month sequential treatment with exenatide and glargine added to metformin basically improved the insulin sensitivity and glucolipid control though VAT rebounded at the end, however without deteriorating the other parameters. Conclusion. Exenatide is an ideal treatment for obese type 2 diabetic patients in the aspect of adipose tissue distribution. Sequential treatment of exenatide and glargine could be an alternative for low-income patients who cannot afford GLP-1 agonist for long time. This trial is registered with ChiCTR-OOC-17013679.

Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes

2010 ◽  
Vol 108 (4) ◽  
pp. 830-837 ◽  
Author(s):  
Mette P. Sonne ◽  
Amra C. Alibegovic ◽  
Lise Højbjerre ◽  
Allan Vaag ◽  
Bente Stallknecht ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
High Sensitivity ◽  
Whole Body ◽  
Diabetic Patients ◽  
Activity Levels ◽  
Type 2 Diabetic Patients ◽  
Increased Risk

Physical inactivity is a known risk factor for type 2 diabetes. We studied whole body and forearm insulin sensitivity in subjects at increased risk for type 2 diabetes [persons with low birth weight (LBW group; n = 20) and first-degree relatives to type 2 diabetic patients (FDR group; n = 13)] as well as a control (CON) group ( n = 20) matched for body mass index, age, and physical activity levels before and after 10 days of bedrest. Subjects were studied by hyperinsulinemic isoglycemic clamp combined with arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. All groups responded with a decrease in whole body insulin sensitivity in response to bedrest [CON group: 6.8 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), LBW group: 6.2 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), and FDR group: 4.3 ± 0.7 to 3.1 ± 0.3 mg·min−1·kg−1( P = 0.068)]. The percent decrease was significantly greater in the CON group compared with the FDR group (CON group: 34 ± 4%, LBW group: 27 ± 4%, and FDR group: 10 ± 13%). Forearm insulin-stimulated glucose clearance decreased significantly in the CON and LBW groups in response to bedrest; in the FDR group, clearance was very low before bedrest and no change was observed. Before bedrest, the CON and LBW groups demonstrated a significant increase in FBF during hyperinsulinemia; after bedrest, an increase in FBF was observed only in the CON group. In conclusion, bedrest induced a pronounced reduction in whole body, skeletal muscle, and vascular insulin sensitivity in the CON and LBW groups. The changes were most pronounced in the CON group. In the FDR group, insulin resistance was already present before bedrest, but even this group displayed a high sensitivity to changes in daily physical activity.

PPARγ-mediated insulin sensitization: the importance of fat versus muscle

2005 ◽  
Vol 288 (2) ◽  
pp. E287-E291 ◽  
Author(s):  
Ulrich Kintscher ◽  
Ronald E. Law
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Nuclear Hormone Receptor ◽  
Whole Body ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Type 2 Diabetic Patients ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peripheral Tissues

Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear hormone receptor that functions as a transcriptional regulator in a variety of tissues. PPARγ activation, e.g., through binding of the synthetic glitazones or thiazolidinediones (TZD), results in a marked improvement in type 2 diabetic patients of insulin and glucose parameters resulting from an improvement of whole body insulin sensitivity. The role of different metabolic tissues (fat, skeletal muscle, liver) in mediating PPARγ function in glucose and insulin homeostasis is still unclear. Recently, the function of PPARγ in adipose tissue and skeletal muscle has been intensively characterized by using targeted deletion of PPARγ in those tissues. In those studies, adipose PPARγ has been identified as an essential mediator for the maintainance of whole body insulin sensitivity. Two major mechanisms have been described. 1) Adipose PPARγ protects nonadipose tissue against excessive lipid overload and maintains normal organ function (liver, skeletal muscle); and 2) adipose PPARγ guarantees a balanced and adequate production of secretion from adipose tissue of adipocytokines such as adiponectin and leptin, which are important mediators of insulin action in peripheral tissues. In contrast to studies in adipose-specific PPARγ-deficient mice, the data in muscle-specific PPARγ−/− mice demonstrate that whole body insulin sensitivity is, at least in part, relying on an intact PPARγ system in skeletal muscle. Finally, these early and elegant studies using tissue-specific PPARγ knockout mouse models pinpoint adipose tissue as the major target of TZD-mediated improvement of hyperlipidemia and insulin sensitization.

Long-Term Oral L-Arginine Administration Improves Peripheral and Hepatic Insulin Sensitivity in Type 2 Diabetic Patients

Diabetes Care ◽  
2001 ◽  
Vol 24 (5) ◽  
pp. 875-880 ◽  
Author(s):  
P. Piatti ◽  
L. D. Monti ◽  
G. Valsecchi ◽  
F. Magni ◽  
E. Setola ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Hepatic Insulin Sensitivity ◽  
Type 2 Diabetic

scholarly journals Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients

2011 ◽  
Vol 106 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Pál Brasnyó ◽  
Gergő A. Molnár ◽  
Márton Mohás ◽  
Lajos Markó ◽  
Boglárka Laczy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Type 2 Diabetic Patients ◽  
Β Cell Function ◽  
Type 2 Diabetic

Although resveratrol has widely been studied for its potential health benefits, little is known about its metabolic effects in humans. Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action. After an initial general examination (including blood chemistry), nineteen patients enrolled in the 4-week-long double-blind study were randomly assigned into two groups: a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo. Before and after the second and fourth weeks of the trial, insulin resistance/sensitivity, creatinine-normalised ortho-tyrosine level in urine samples (as a measure of oxidative stress), incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B (Akt) ratio in platelets were assessed and statistically analysed. After the fourth week, resveratrol significantly decreased insulin resistance (homeostasis model of assessment for insulin resistance) and urinary ortho-tyrosine excretion, while it increased the pAkt:Akt ratio in platelets. On the other hand, it had no effect on parameters that relate to β-cell function (i.e. homeostasis model of assessment of β-cell function). The present study shows for the first time that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway.

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