Effect of Concomitant Administration of L-Glutamine and Cycloart-23-ene-3β, 25-diol (B2) with Sitagliptin in GLP-1 (7–36) Amide Secretion, Biochemical and Oxidative Stress in Streptozotocin - Nicotinamide Induced Diabetic Sprague Dawley Rats

Abstract

Previously we have reported that, cycloart-23-ene-3β, 25-diol (called as B2) and L-glutamine stimulated glucagon like peptide-1 (GLP-1) (7–36) amide secretion diabetic rats. The objective of present investigation was to investigate the concomitant administration of cycloart-23-ene-3β, 25-diol+sitagliptin and L-glutamine+sitagliptin in streptozotocin - nicotinamide induced diabetic Sprague Dawley. Type 2 diabetes was induced in overnight fasted male Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into; I- non-diabetic, II- diabetic control, III- Sitagliptin (5 mg/kg, p.o.)+cycloart-23-ene-3β, 25-diol (1 mg/kg, p.o.), IV- Sitagliptin (5 mg/kg, p.o.)+L-glutamine (1000 mg/kg, p.o.). The concomitant treatment of cycloart-23-ene-3β, 25-diol and L-glutamine with sitagliptin was 8 weeks. Plasma glucose, body weight, food and water intake were determined every week. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7–36) amide, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress were measured after 8th week treatment. Concomitant administration of cycloart-23-ene-3β, 25-diol and L-glutamine with sitagliptin significantly (p<0.001) reduced plasma glucose, glyoxylated haemoglobin, lipid profile and oxidative stress parameters compared to diabetic control groups. Both concomitant treatment increased plasma and pancreatic insulin as well as plasma and colonic active (GLP-1) (7–36) amide secretion. Histological analysis by Gomori staining observed less destruction of pancreatic β cells. The result obtained from this study; it is concluded that concomitant administration of cycloart-23-ene-3β, 25-diol+sitagliptin and L-glutamine+sitagliptin showed additive antihyperglycaemic effect in diabetic rats.

A comprehensive insight into the effect of glutamine supplementation on metabolic variables in diabetes mellitus: a systematic review

“…Diabetic fed with a common semi purified diet, 3. Identical diet with glutamine 25% of total amino acid nitrogen 8 weeks Significant increase GSH Significant decrease CRP, IL-6, IL-23, MCP-1 No significant change Fasting blood Glucose, TGF-β, TNF-α, IL-17A Badole et al, India, 2013 [ 18 ] Rats divided into six groups: 1. Nondiabetic, 2.…”

“…Glutamine 500 mg/kg 6. Glutamine 1000 mg/kg 250–500-1000 mg/kg 8 weeks Significant decrease MDA, fasting blood glucose, LDL,TC, TG Significant increase Plasma and pancreatic insulin, increased GLP-1, amide secretion, GSH, SOD, GPx (only the highest dose), HDL Bdaole et al, India, 2013 [ 18 ] Rats divided into four groups: 1. Non-diabetic, 2.…”

Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats

“…The neuroprotection caused by L-glutamine in the diabetic group (DG) in this study has been reported in the literature for vipergic [ 12 , 53 ] and general [ 64 ] populations. Supplementation with L-glutamine has proven effective in minimize oxidative stress [ 22 , 28 , 65 , 66 ], increasing its availability to tissues under stress [ 67 ]. The GDP also has antioxidant potential [ 65 ], but its supplementation was not able to protect the submucous neurons.…”

The anti-hyperglycemic efficacy of a lipid-lowering drug Daming capsule and the underlying signaling mechanisms in a rat model of diabetes mellitus

“…The essential roles of GLP-1 and GIP in maintaining blood glucose homeostasis have been widely recognized. GLP-1 is an incretin secreted from the intestinal L cells, which regulates blood glucose homeostasis via stimulation of insulin secretion, attenuation of gastric emptying and promotion of satiety 17 38 39 . Many drugs and Chinese herbal medicines improve diabetes by regulating GLP-1 40 .…”

“…As an anti-hyperglycemic hormone it acts by stimulating glucose-dependent insulin secretion 13 14 15 . In addition, GLP-1 inhibits gastric secretion and regulates glucose homeostasis in the gastrointestinal tract after meals and is required for normal glucose tolerance 16 17 . Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid peptide localized to the distal intestine, where exists a population of K-/L cells that produce both GIP and GLP-1.…”