Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression
Siyun Li,1 Fuzhen Feng,2 Yanhui Deng1 1Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pharmacy, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, People’s Repub...
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Dove Medical Press
2023-04-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
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| Online Access: | https://www.dovepress.com/resveratrol-regulates-glucose-and-lipid-metabolism-in-diabetic-rats-by-peer-reviewed-fulltext-article-DMSO |
| _version_ | 1797845673200058368 |
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| author | Li S Feng F Deng Y |
| author_facet | Li S Feng F Deng Y |
| author_sort | Li S |
| collection | DOAJ |
| description | Siyun Li,1 Fuzhen Feng,2 Yanhui Deng1 1Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pharmacy, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, People’s Republic of ChinaCorrespondence: Yanhui Deng, Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Road, Tianhe District, Guangzhou, 510630, People’s Republic of China, Tel +86 020 62784810, Email shiningdyh@sina.comPurpose: 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 Hif-1α, Glut1 and Ldlr in the liver were determined by RT-qPCR.Results: RSV treatment significantly reduced liver/body weight ratio (L/W, P < 0.05), FBG (P < 0.01) and serum concentrations of total cholesterol (TC, P < 0.05), triglycerides (TG, P < 0.01) and low-density lipoprotein-cholesterol (LDL-C, P < 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 (P < 0.01) and the levels of HIF-1α (P < 0.05) and GLUT1 (P < 0.01), while significantly upregulating the level of LDLR (P < 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.Keywords: resveratrol, diabetes, glycolipid metabolism, PDK1, AKT, HIF-1α |
| first_indexed | 2024-04-09T17:42:48Z |
| format | Article |
| id | doaj.art-70b7380969744a278cd73c4b5aeaf30b |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-09T17:42:48Z |
| publishDate | 2023-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-70b7380969744a278cd73c4b5aeaf30b2023-04-16T17:51:26ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072023-04-01Volume 161063107483046Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α ExpressionLi SFeng FDeng YSiyun Li,1 Fuzhen Feng,2 Yanhui Deng1 1Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pharmacy, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, People’s Republic of ChinaCorrespondence: Yanhui Deng, Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Road, Tianhe District, Guangzhou, 510630, People’s Republic of China, Tel +86 020 62784810, Email shiningdyh@sina.comPurpose: 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 Hif-1α, Glut1 and Ldlr in the liver were determined by RT-qPCR.Results: RSV treatment significantly reduced liver/body weight ratio (L/W, P < 0.05), FBG (P < 0.01) and serum concentrations of total cholesterol (TC, P < 0.05), triglycerides (TG, P < 0.01) and low-density lipoprotein-cholesterol (LDL-C, P < 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 (P < 0.01) and the levels of HIF-1α (P < 0.05) and GLUT1 (P < 0.01), while significantly upregulating the level of LDLR (P < 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.Keywords: resveratrol, diabetes, glycolipid metabolism, PDK1, AKT, HIF-1αhttps://www.dovepress.com/resveratrol-regulates-glucose-and-lipid-metabolism-in-diabetic-rats-by-peer-reviewed-fulltext-article-DMSOresveratroldiabetesglycolipid metabolismpdk1akthif-1α |
| spellingShingle | Li S Feng F Deng Y Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression Diabetes, Metabolic Syndrome and Obesity resveratrol diabetes glycolipid metabolism pdk1 akt hif-1α |
| title | Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression |
| title_full | Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression |
| title_fullStr | Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression |
| title_full_unstemmed | Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression |
| title_short | Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression |
| title_sort | resveratrol regulates glucose and lipid metabolism in diabetic rats by inhibition of pdk1 akt phosphorylation and hif 1 alpha expression |
| topic | resveratrol diabetes glycolipid metabolism pdk1 akt hif-1α |
| url | https://www.dovepress.com/resveratrol-regulates-glucose-and-lipid-metabolism-in-diabetic-rats-by-peer-reviewed-fulltext-article-DMSO |
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