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Effect of siglidine on glucose lipid metabolism and the expression of iNOS and GLP-1 receptors in diabetic rats.
- Source :
-
European review for medical and pharmacological sciences [Eur Rev Med Pharmacol Sci] 2018 Dec; Vol. 22 (24), pp. 8984-8989. - Publication Year :
- 2018
-
Abstract
- Objective: Diabetic nephropathy (DN) has become the major complication of diabetes. The progression of the disease impedes the efficacy of DN treatment. Therefore, the strategies to inhibit or reverse kidney damage in DN patients are of critical importance. We aim to investigate the effect of sitagliptin on DN within rat model and analyze the associated metabolism and expression of iNOS/GLP-1 receptor.<br />Materials and Methods: Diabetic model was generated by using Sprague-Dawley (SD) rats, which received an intra-peritoneal injection of 30 mg/kg streptozotocin. Rats were then treated with saline or 15 mg/(kg.d) sitagliptin by gavage. After 12 weeks, fasting blood glucose and insulin resistance were measured. Rat glucose and lipid metabolism were evaluated by high triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Western blot was used to measure expression of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) related with glucose-lipid metabolism, and expression of iNOS and GLP-1 expression in kidney tissues.<br />Results: After 12 weeks of feeding, the levels of blood glucose and lipid in sitagliptin group were significantly decreased compared to those in control group (p<0.05), whilst insulin sensitivity was enhanced (p<0.05). Western blot showed that sitagliptin downregulated the expressions of glucose-lipid metabolism proteins such as G6Pase, PEPCK, ACC and FAS in rat livers, inhibited iNOS expression in kidneys and elevated GLP-1 receptor activity (p<0.05).<br />Conclusions: Sitagliptin effectively stabilizes blood glucose and lipid levels in DN rats, significantly improves glucose-lipid metabolism and protects kidney and vascular endothelial cells during DN pathogenesis through inhibiting iNOS expression and elevating GLP-1 receptor activity.
- Subjects :
- Animals
Biomarkers
Blood Glucose metabolism
Diabetes Mellitus, Experimental blood
Diabetes Mellitus, Experimental enzymology
Diabetic Nephropathies blood
Diabetic Nephropathies enzymology
Energy Metabolism drug effects
Glucagon-Like Peptide-1 Receptor genetics
Kidney enzymology
Liver drug effects
Liver enzymology
Male
Nitric Oxide Synthase Type II genetics
Rats, Sprague-Dawley
Blood Glucose drug effects
Diabetes Mellitus, Experimental drug therapy
Diabetic Nephropathies prevention & control
Dipeptidyl-Peptidase IV Inhibitors pharmacology
Glucagon-Like Peptide-1 Receptor metabolism
Kidney drug effects
Lipids blood
Nitric Oxide Synthase Type II metabolism
Sitagliptin Phosphate pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2284-0729
- Volume :
- 22
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- European review for medical and pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 30575943
- Full Text :
- https://doi.org/10.26355/eurrev_201812_16669