Oral l-glutamine increases active GLP-1 (7-36) amide secretion and improves glycemic control in stretpozotocin-nicotinamide induced diabetic rats

l-glutamine is a non-essential amino acid. It decreased blood sugar, stimulated insulin secretion in type 2 diabetic patients. The objective of the present investigation was to evaluate l-glutamine increases glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide (STZ-NTM) induced diabetic Sprague Dawley rats. Molecular docking study was performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by 20 min after administration of streptozotocin (55 mg/kg, i.p.). The rats were divided into; I - nondiabetic, II - diabetic control, III - sitagliptin (5 mg/kg, p.o.), IV - l-glutamine (250 mg/kg, p.o.), V - l-glutamine (500 mg/kg, p.o.) and VI - l-glutamine (1000 mg/kg, p.o.). The l-glutamine and sitagliptin treatment was 8 week. Plasma glucose was estimated every week. Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagon GLP-1, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8 week. In acute study, the rats were divided into I - glucose (2.5 g/kg, p.o.), II - sitagliptin (5 mg/kg, p.o.), III - l-glutamine (250 mg/kg, p.o.), IV - l-glutamine (500 mg/kg, p.o.) and V - l-glutamine (1000 mg/kg, p.o.). Plasma glucose, active GLP-1 (7-36) amide concentration and insulin levels were measured after glucose loading. The docking data indicated that l-glutamine bind to the GLP-1 receptor. l-glutamine decreased plasma glucose, increased plasma and pancreatic insulin, increased plasma and colonic active GLP-1 (7-36) amide secretion as well as decreased oxidative stress in streptozotocin-nicotinamide induced diabetic rats.

Graphical abstractDownload full-size imageHighlights► We find out l-glutamine increased glucagon like peptide-1. ► It increased mRNA expression for GLP-1. ► It improved glycemia, insulin release and active GLP-1 (7-36) amide secretion. ► l-glutamine decreased oxidative stress. ► l-glutamine useful in treatment of diabetes mellitus.