Abstract

[Purpose]Exercise training with PPARγ agonist is expected to increase glucose uptake and improve insulin sensitivity in skeletal muscle of patients with diabetes. However, its mechanisms to effect glucose uptake and insulin sensitivity in skeletal muscle are unclear.[Methods]The mechanism of action was determined by co-treatment with PPARγ agonist- rosiglitazone and exercise training in streptozotocin induced-diabetic obese Zucker rats. Exercise training was carried out for 6 weeks (swimming, 1 h/day, 5 times/week, 5% weight/g, 32±1℃) with rosiglitazone treatment (3mg/kg/day, 6weeks).[Results]Glucose uptake and insulin sensitivity was decreased in diabetic than normal animals. Exercise training and rosiglitazone treatment respectively increased the expression of PPAR(peroxisome proliferators-activated receptor)-α, -β/δ, -γ, PGC-1α(PPAR-γ coactivator-1α), adiponectin, GLUT-4(glucose transportor-4) and p-AMPK-α2(phospho-AMP activated protein kinase-α2) in EDL and SOL of diabetic, as compared to normal animals. Interestingly, training combined with rosiglitazone significantly increased glucose uptake and insulin sensitivity, which resulted in high expression of all molecules in diabetic than all other groups.[Conclusion]These results indicated that exercise training combined with rosiglitazone might mediate regulation of glucose uptake and insulin sensitivity in skeletal muscle. Therefore, exercise training combined with rosiglitazone may be recommended as complementary therapies for diabetes.

Highlights

  • Obesity and type II diabetes are characterized by impaired glucose uptake and reduced fatty acid oxidation

  • [Conclusion] These results indicated that exercise training combined with rosiglitazone might mediate regulation of glucose uptake and insulin sensitivity in skeletal muscle

  • Studies suggest that administration of TZD to obese animal models with insulin resistance and diabetes patients can lead to the improvement of glucose uptake and insulin sensitivity associated with increasing glucose transportor-4 (GLUT-4), AMP activated protein kinase (AMPK), and peroxisome proliferators-activated receptor (PPARs)-γ coactivator-1α (PGC-1)[13, 20]

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Summary

Introduction

Obesity and type II diabetes are characterized by impaired glucose uptake and reduced fatty acid oxidation. Reduced fatty acids oxidation is known to cause insulin resistance, in skeletal muscle[8, 28]. Skeletal muscle is responsible for majority (>80%) of insulin-stimulated whole body glucose disposal, and plays an important role in the pathogenesis of insulin resistance and diabetes[28]. The thiazolidinediones (TZDs) are known peroxisome proliferators-activated receptor (PPARs) agonists and major compounds for the treatment of type 2 diabetes. Studies suggest that administration of TZD to obese animal models with insulin resistance and diabetes patients can lead to the improvement of glucose uptake and insulin sensitivity associated with increasing glucose transportor-4 (GLUT-4), AMP activated protein kinase (AMPK), and PPAR-γ coactivator-1α (PGC-1)[13, 20]

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