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Resveratrol Affects Insulin Signaling in Type 2 Diabetic Goto-Kakizaki Rats
Katarzyna Szkudelska1, Marzanna Deniziak2, Maciej Sassek1
1Department of Animal Physiology, Biochemistry and Biostructure, Poznan University of Life Sciences, Wolynska 35, 60-637 Poznan, Poland.
Abstract:
Resveratrol is a biologically active diphenolic compound exerting multiple beneficial effects in the organism, including anti-diabetic properties. This action is, however, not fully elucidated. In the present study, we examined effects of resveratrol on some parameters related to insulin signaling, and also on diabetes-associated dysregulation in Goto-Kakizaki (GK) rats with congenital type 2 diabetes. Resveratrol was given at the dose of 20 mg/kg b.w. for 10 weeks. It was shown that the expression and phosphorylation levels of insulin receptor in the skeletal muscle of GK rats were significantly decreased, compared with control animals. However, these changes were totally prevented by resveratrol. Liver expression of the insulin receptor was also reduced, but in this case, resveratrol was ineffective. Resveratrol was also demonstrated to significantly influence parameters of insulin binding (dissociation constant and binding capacity) in the skeletal muscle and liver. Moreover, it was shown that the expression levels of proteins related to intracellular glucose transport (GLUT4 and TUG) in adipose tissue of GK rats were significantly decreased. However, treatment with resveratrol completely abolished these changes. Resveratrol was found to induce normalization of TUG expression in the skeletal muscle. Blood levels of insulin and GIP were elevated, whereas proinsulin and GLP-1 diminished in GK rats. However, concentrations of these hormones were not affected by resveratrol. These results indicate that resveratrol partially ameliorates diabetes-associated dysregulation in GK rats. The most relevant finding covers the normalization of the insulin receptor expression in the skeletal muscle and also GLUT4 and TUG in adipose tissue.
Insights
Resveratrol treatment improved type 2 diabetes in Goto-Kakizaki rats by normalizing insulin receptor expression in skeletal muscle and glucose transporters in adipose tissue. This suggests a potential therapeutic role for resveratrol in managing diabetes.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- Resveratrol, a diphenolic compound, exhibits beneficial effects, including anti-diabetic properties, though its mechanisms are not fully understood.
- Type 2 diabetes is characterized by dysregulation of insulin signaling and glucose transport.
- Goto-Kakizaki (GK) rats serve as a model for congenital type 2 diabetes.
Purpose of the Study:
- To investigate the effects of resveratrol on insulin signaling pathways.
- To evaluate resveratrol's impact on diabetes-associated dysregulation in GK rats.
- To elucidate the molecular mechanisms underlying resveratrol's anti-diabetic actions.
Main Methods:
- GK rats were administered resveratrol (20 mg/kg b.w.) for 10 weeks.
- Insulin receptor expression and phosphorylation were analyzed in skeletal muscle and liver.
- Insulin binding parameters (dissociation constant, binding capacity) were assessed.
- Expression levels of glucose transporters (GLUT4, TUG) in adipose tissue and skeletal muscle were measured.
- Blood levels of insulin, proinsulin, GIP, and GLP-1 were determined.
Main Results:
- Resveratrol prevented decreased insulin receptor expression and phosphorylation in GK rat skeletal muscle.
- Resveratrol normalized insulin binding parameters in skeletal muscle and liver.
- Resveratrol treatment abolished decreased expression of GLUT4 and TUG in adipose tissue.
- Resveratrol normalized TUG expression in skeletal muscle.
- Resveratrol did not significantly alter blood levels of insulin, proinsulin, GIP, or GLP-1.
Conclusions:
- Resveratrol partially ameliorates diabetes-associated dysregulation in GK rats.
- Key findings include normalization of insulin receptor expression in skeletal muscle and glucose transporters (GLUT4, TUG) in adipose tissue.
- Resveratrol demonstrates potential as a therapeutic agent for type 2 diabetes by improving insulin sensitivity and glucose uptake.
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