Lu Shou-Si, Yu Yun-Li, Zhu Hao-Jie, Liu Xiao-Dong, Liu Li, Liu Yao-Wu, Wang Ping, Xie Lin, Wang Guang-Ji
Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
J Endocrinol. 2009 Feb;200(2):159-65. doi: 10.1677/JOE-08-0419. Epub 2008 Nov 7.
Berberine (BBR), a hypoglycemic agent, has shown beneficial metabolic effects for anti-diabetes, but its precise mechanism was unclear. Glucagon-like peptide-1 (GLP-1) is considered to be an important incretin that can decrease hyperglycemia in the gastrointestinal tract after meals. The aim of this study was to investigate whether BBR exerts its anti-diabetic effects via modulating GCG secretion. Diabetes-like rats induced by streptozotocin received BBR (120 mg/kg per day, i.g) for 5 weeks. Two hours following the last dose, the rats were anaesthetized and received 2.5 g/kg glucose by gavage. At 15-minute and 30-minute after glucose load, blood samples, pancreas, and intestines were obtained to measure insulin and GCG using ELISA kit. The number of L cells in the ileum and beta-cells in the pancreas were identified using immunohistology. The expression of proglucagon mRNA in the ileum was measured by RT-PCR. The results indicated that BBR treatment significantly increased GCG levels in plasma and intestine (P<0.05) accompanied with the increase of proglucagon mRNA expression and the number of L-cell compared with the controls (P<0.05). Furthermore, BBR increased insulin levels in plasma and pancreas as well as beta-cell number in pancreas. The data support the hypothesis that the anti-diabetic effects of BBR may partly result from enhancing GCG secretion.
黄连素(BBR)是一种降血糖药物,已显示出对糖尿病有益的代谢作用,但其确切机制尚不清楚。胰高血糖素样肽-1(GLP-1)被认为是一种重要的肠促胰岛素,可在餐后降低胃肠道中的高血糖水平。本研究的目的是探讨BBR是否通过调节胰高血糖素(GCG)分泌发挥其抗糖尿病作用。用链脲佐菌素诱导的糖尿病样大鼠接受BBR(每天120mg/kg,灌胃)治疗5周。在最后一剂给药后2小时,将大鼠麻醉并通过灌胃给予2.5g/kg葡萄糖。在葡萄糖负荷后15分钟和30分钟,采集血液样本、胰腺和肠道,使用ELISA试剂盒测量胰岛素和GCG。使用免疫组织学鉴定回肠中的L细胞和胰腺中的β细胞数量。通过RT-PCR测量回肠中胰高血糖素原mRNA的表达。结果表明,与对照组相比,BBR治疗显著提高了血浆和肠道中的GCG水平(P<0.05),同时胰高血糖素原mRNA表达和L细胞数量增加(P<0.05)。此外,BBR增加了血浆和胰腺中的胰岛素水平以及胰腺中的β细胞数量。这些数据支持了BBR的抗糖尿病作用可能部分源于增强GCG分泌这一假说。