Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2023 Apr 24

PMID 37090841

Authors

Siyun Li

Fuzhen Feng

Yanhui Deng

Affiliations

Soon will be listed here.

Abstract

Purpose: To explore the underlying mechanism of the anti-diabetic effect of resveratrol (RSV) on regulating glycolipid metabolism in diabetic rats induced by streptozotocin (STZ) and a high-fat diet (HFD).

Methods: Male Wistar rats were randomized into three groups. Two groups were fed a high-fat diet and intraperitoneally injected with STZ (35 mg/kg), with one group also treated with RSV (30 mg/kg/d), and the third, control group was fed a normal diet. After 12 weeks, blood lipid levels and fasting blood glucose (FBG) were assessed. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The protein expression of hypoxia-inducible factor 1α (HIF-1α) was assessed by Western blotting and immunofluorescence, and the proteins level of 3-phosphoinositide-dependent protein kinase 1 (PDK1), phosphorylated-PDK1 (p-PDK1), phosphorylated-protein kinase B (p-AKT), glucose transporter 1 (GLUT1) and low-density lipoprotein receptor (LDLR) in the liver were analyzed by Western blotting. The mRNA levels of and in the liver were determined by RT-qPCR.

Results: RSV treatment significantly reduced liver/body weight ratio (L/W, < 0.05), FBG ( < 0.01) and serum concentrations of total cholesterol (TC, < 0.05), triglycerides (TG, < 0.01) and low-density lipoprotein-cholesterol (LDL-C, < 0.05) in diabetic rats. RSV also improved diabetic symptoms, attenuated liver steatosis and increased liver glycogen accumulation. RSV treatment significantly downregulated the proteins expression of p-PDK1 and p-AKT ( < 0.01) and the levels of HIF-1α ( < 0.05) and GLUT1 ( < 0.01), while significantly upregulating the level of LDLR ( < 0.05).

Conclusion: RSV was effective in improving glycolipid metabolism in diabetic rats, probably by inhibiting the PDK1/AKT/HIF-1α pathway and regulation of its downstream target levels. These findings may provide new insight into the mechanism of action of RSV in the treatment of diabetes.

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