Ministry of Health, Kuwait City, Kuwait.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Pharmacol Rep. 2018 Apr;70(2):233-242. doi: 10.1016/j.pharep.2017.10.009. Epub 2017 Oct 25.
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).
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).
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.
Addition of glutamine to liraglutide regimen enhances the glycemic control and may have utility in clinical settings.
谷氨酰胺氨基酸调节胰岛β细胞的胰岛素分泌。利拉鲁肽是一种胰高血糖素样肽-1（GLP-1）类似物，它在抑制β细胞凋亡和保护胰岛β细胞量方面具有令人着迷的作用。本研究调查了在糖尿病大鼠中添加谷氨酰胺对利拉鲁肽治疗方案的益处，重点研究其在增加胰岛素产生和上调钠依赖性中性氨基酸转运体-2（SNAT2）表达方面的作用。
在本研究中，使用链脲佐菌素（STZ，50mg/kg，ip）诱导大鼠糖尿病。雄性大鼠被分为 5 组，（i）载体组，（ii）STZ 糖尿病大鼠，（iii）用利拉鲁肽（150μg/kg，sc）治疗的 STZ 糖尿病大鼠，（iv）用谷氨酰胺（po）治疗的 STZ 糖尿病大鼠和（v）用利拉鲁肽和谷氨酰胺联合治疗的 STZ 糖尿病大鼠四周。完成治疗疗程后，测定空腹血糖值，处死大鼠。胰腺用于定量 SNAT2 的 mRNA 表达。石蜡固定样本用于胰岛素和凋亡标志物（活化的 caspase-3、BCL2 和 BAX）的组织学染色和免疫组织化学。
利拉鲁肽和/或谷氨酰胺的治疗增强了糖尿病雄性大鼠的胰岛素产生和血糖控制，对凋亡标志物有有利影响。谷氨酰胺及其与利拉鲁肽的联合治疗显著增加了胰腺 SNAT2 的表达，约增加了 30-35 倍。
将谷氨酰胺添加到利拉鲁肽方案中可增强血糖控制，在临床环境中可能具有实用性。
