Zekrayat J H Medras1, Norhan M El-Sayed2, Sawsan A Zaitone3, Eman A Toraih4, Manal M Sami5, Yasser M Moustafa2. 1. Ministry of Health, Kuwait City, Kuwait. 2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt. 3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. Electronic address: sawsan_zaytoon@pharm.suez.edu.eg. 4. Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. 5. Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Abstract
BACKGROUND: Glutamine aminoacid regulates insulin exocytosis from pancreatic β-cells. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has fascinated function in inhibiting β-cell apoptosis and preserving pancreatic β-cell mass. The present study investigated the benefit of adding glutamine to a regimen of liraglutide in diabetic rats focusing on their role in increasing insulin production and upregulation of the expression of sodium-dependent neutral aminoacid transporter-2 (SNAT2). METHODS: In the present study, diabetes mellitus was induced in rats using streptozotocin (STZ, 50mg/kg, ip). Male rats were allocated into 5 groups, (i) vehicle group, (ii) STZ-diabetic rats, (iii) STZ-diabetic rats treated with liraglutide (150μg/kg, sc), (iv) STZ-diabetic rats treated with glutamine (po) and (v) STZ-diabetic rats treated with a combination of liraglutide and glutamine for four weeks. After finishing the therapeutic courses, the fasting blood glucose value was determined and rats were sacrificed. Pancreases were used for quantification of mRNA expression for SNAT2. Paraffin fixed samples were used for histologic staining and immunohistochemistry for insulin and apoptosis markers (activated caspase-3, BCL2 and BAX). RESULTS: Treatment with liraglutide and/or glutamine enhanced insulin production and hence glycemic control in diabetic male rats with favorable effects on apoptosis markers. Treatment with glutamine and its combination with liraglutide significantly increased pancreatic expression of SNAT2 by approximately 30-35 folds. CONCLUSION: Addition of glutamine to liraglutide regimen enhances the glycemic control and may have utility in clinical settings.
BACKGROUND:Glutamine aminoacid regulates insulin exocytosis from pancreatic β-cells. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has fascinated function in inhibiting β-cell apoptosis and preserving pancreatic β-cell mass. The present study investigated the benefit of adding glutamine to a regimen of liraglutide in diabeticrats focusing on their role in increasing insulin production and upregulation of the expression of sodium-dependent neutral aminoacid transporter-2 (SNAT2). METHODS: In the present study, diabetes mellitus was induced in rats using streptozotocin (STZ, 50mg/kg, ip). Male rats were allocated into 5 groups, (i) vehicle group, (ii) STZ-diabeticrats, (iii) STZ-diabeticrats treated with liraglutide (150μg/kg, sc), (iv) STZ-diabeticrats treated with glutamine (po) and (v) STZ-diabeticrats treated with a combination of liraglutide and glutamine for four weeks. After finishing the therapeutic courses, the fasting blood glucose value was determined and rats were sacrificed. Pancreases were used for quantification of mRNA expression for SNAT2. Paraffin fixed samples were used for histologic staining and immunohistochemistry for insulin and apoptosis markers (activated caspase-3, BCL2 and BAX). RESULTS: Treatment with liraglutide and/or glutamine enhanced insulin production and hence glycemic control in diabetic male rats with favorable effects on apoptosis markers. Treatment with glutamine and its combination with liraglutide significantly increased pancreatic expression of SNAT2 by approximately 30-35 folds. CONCLUSION: Addition of glutamine to liraglutide regimen enhances the glycemic control and may have utility in clinical settings.