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.

Highlights

  • Resveratrol (3,5,3 -trihydroxystilbene) is a naturally occurring bioactive compound present in different plant species

  • Indices related to insulin resistance, such as fasting insulin/glucose ratio (FIGR), homeostatic model assessment— insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI), were measured in fasted animals

  • Results of our study have shown that values of HOMAIR were significantly increased (p < 0.05), QUICKI decreased (p < 0.05), and FIGR remained

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Summary

Introduction

Resveratrol (3,5,3 -trihydroxystilbene) is a naturally occurring bioactive compound present in different plant species. Results of animal studies and human clinical trials indicate that resveratrol has a great potential to alleviate dysregulation occurring in type 2 diabetes [2,3]. Results of numerous studies have provided evidence that in animals with experimentally induced type 2 diabetes, resveratrol treatment is associated with the decline in blood glucose levels. Results of human studies and clinical trials indicate that resveratrol therapy markedly reduces blood glucose levels and improves insulin action in patients with type 2 diabetes [9,10,11,12,13,14]. The beneficial effects of resveratrol related to blood glucose levels and insulin resistance were not confirmed in other studies on humans with type 2 diabetes [2,15,16]. We mainly focused on parameters related to insulin signaling, levels of some hormones, and expression of proteins involved in the intracellular glucose transport

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