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

• Published in: Chemico-biological interactions 2013-04, Vol.203 (2), p.530-541
• Main Authors: Badole, Sachin L., Bagul, Pranita P., Mahamuni, Sagar P., Khose, Rekha D., Joshi, Anuja C., Jangam, Ganesh B., Ghule, Arvindkumar E., Raut, Chandrashekhar G., Khedkar, Vijay M., Coutinho, Evans C.
• Format: Article
• Language: English
• Subjects: Administration, Oral; amino acids; Animals; Antioxidant parameters; biomarkers; blood glucose; Blood Glucose - metabolism; body weight; Body Weight - drug effects; Colon - drug effects; Colon - metabolism; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Docking; Drinking - drug effects; gene expression; Gene Expression Regulation - drug effects; GLP-1 (7-36) amide; glucagon; glucagon-like peptide 1; Glucagon-Like Peptide 1 - blood; Glucagon-Like Peptide 1 - genetics; Glucagon-Like Peptide 1 - metabolism; Glucagon-Like Peptide 1 - secretion; Glucagon-Like Peptide-1 Receptor; glucose; Glucose Tolerance Test; Glutamine - administration & dosage; Glutamine - metabolism; Glutamine - pharmacology; glutathione; glutathione peroxidase; Glycated Hemoglobin A - metabolism; glycemic control; glycosylation; hemoglobin; histology; insulin; Insulin - blood; Insulin - metabolism; Insulin secretion; l-glutamine; Lipid Metabolism - drug effects; Male; malondialdehyde; messenger RNA; Molecular Docking Simulation; Niacinamide - adverse effects; nicotinamide; noninsulin-dependent diabetes mellitus; oxidative stress; Oxidative Stress - drug effects; Pancreas - drug effects; Pancreas - metabolism; Pancreas - pathology; patients; Peptide Fragments - blood; Peptide Fragments - genetics; Peptide Fragments - metabolism; Peptide Fragments - secretion; Proglucagon gene expression; Protein Conformation; Pyrazines - administration & dosage; Pyrazines - metabolism; Pyrazines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Glucagon - chemistry; Receptors, Glucagon - metabolism; Sitagliptin Phosphate; streptozotocin; Triazoles - administration & dosage; Triazoles - metabolism; Triazoles - pharmacology
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2013.02.006

[Display omitted] ► 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. 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 (100mg/kg, i.p.) followed by 20min after administration of streptozotocin (55mg/kg, i.p.). The rats were divided into; I – nondiabetic, II – diabetic control, III – sitagliptin (5mg/kg, p.o.), IV –l-glutamine (250mg/kg, p.o.), V –l-glutamine (500mg/kg, p.o.) and VI –l-glutamine (1000mg/kg, p.o.). The l-glutamine and sitagliptin treatment was 8week. 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 8week. In acute study, the rats were divided into I – glucose (2.5g/kg, p.o.), II – sitagliptin (5mg/kg, p.o.), III –l-glutamine (250mg/kg, p.o.), IV –l-glutamine (500mg/kg, p.o.) and V –l-glutamine (1000mg/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.