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Journal of ZheJiang University(Medical Science)  2016, Vol. 45 Issue (5): 486-492    DOI: 10.3785/j.issn.1008-9292.2016.09.06
Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-Ⅳ
WANG Jiesheng1, DAI Guanhai2, LI Weijia3
1. Department of Cadre Health, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China;
2. Basic Laboratory, Institute of Traditional Chinese Medicine of Zhejiang Province, Hangzhou 310007, China;
3. Department of Endocrinology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
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Objective: To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms. Methods: Diabetic-like rat model was successfully induced by intraperitoneal injection of streptozotocin in 50 out of 60 male SD rats, which were then randomly divided into 5 groups with 10 rats in each:control group (received vehicle only), positive drug control group (sitagliptin 10 mg·kg-1·d-1), low-dose berberine group (30 mg·kg-1·d-1), moderate-dose berberine group (60 mg·kg-1·d-1), and high-dose berberine group (120 mg·kg-1·d-1). All animals were fed for 3 d, and fasting blood sampling was performed on day 3 of administration. Rats were given glucose (2 g/kg) by gavage 30 min after the last dose. Blood and intestinal samples were obtained 2 h after glucose loading. Fasting blood glucose (FBG) and 2-h postprandial plasma glucose (2h-PPG) were detected by using biochemical analyzer, and insulin, glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-Ⅳ(DPP-Ⅳ) were measured by using ELISA kit. Results: No significant difference in FBG and serum DPP-Ⅳ level were found between berberine groups and control group (all P>0.05). Compared with control group, serum levels of GLP-1 and insulin were increased in high-and moderate-dose berberine groups, while 2h-PPG was decreased (all P<0.05); GLP-1 levels in the intestinal samples were increased, while DPP-Ⅳ levels were decreased in all berberine groups (all P<0.05). Conclusions: Short-term berberine administration can decrease 2h-PPG level in streptozotocin-induced diabetic rat model through local inhibition of intestinal DPP-Ⅳ. The efficacy of DPP-Ⅳ inhibitor may be associated with its intestinal pharmacokinetics.

Key wordsDiabetes mellitus/drug therapy      Berberine/pharmacology      Berberine/administration &      dosage      Glucagon-like peptide 1/drug effects      Antigens, CD26/drug effects      Blood glucose/blood      Diabetes mellitus, experimental     
Received: 19 January 2016      Published: 25 September 2016
CLC:  R587.1  
Cite this article:

WANG Jiesheng, DAI Guanhai, LI Weijia. Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-Ⅳ. Journal of ZheJiang University(Medical Science), 2016, 45(5): 486-492.

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目的:探讨短疗程口服小檗碱对糖尿病大鼠模型的作用及相关机制。方法:取健康雄性SD大鼠60只,采用腹腔注射链脲佐菌素建立糖尿病大鼠模型,其中造模成功50只,按照每天灌喂不同药物将大鼠随机分为五组:模型对照组,西格列汀组(磷酸西格列汀10 mg/kg)和小檗碱小剂量组(小檗碱30 mg/kg)、中剂量组(小檗碱60 mg/kg)、大剂量组(小檗碱120 mg/kg)。第三天早晨空腹采血,喂药后半小时予灌喂50%葡萄糖水(2 g/kg),灌喂葡萄糖2 h时采集血液和肠道标本,采用生化分析仪检测空腹血糖及餐后2 h血糖,采用ELISA法检测餐后2 h血胰岛素、胰高血糖素样肽-1(GLP-1)、二肽基肽酶-Ⅳ(DPP-Ⅳ)及局部肠道组织GLP-1、DPP-Ⅳ含量。结果:干预后小檗碱各剂量组的空腹血糖水平、餐后2 h血DPP-Ⅳ水平与模型对照组差异无统计学意义(均P>0.05);小檗碱中、大剂量组的餐后2 h血GLP-1水平、血胰岛素水平比模型对照组升高,餐后2 h血糖水平比模型对照组降低(均P<0.05);小檗碱各剂量组的肠道组织餐后2 h GLP-1含量比模型对照组增加,餐后2 h肠道组织DPP-Ⅳ含量比模型对照组减少(均P<0.05)。结论:短疗程口服中、大剂量小檗碱能降低糖尿病大鼠模型的餐后血糖,抑制肠道局部的DPP-Ⅳ可能是口服小檗碱的降糖机制之一,DPP-Ⅳ抑制剂的疗效可能与该药的肠道药代动力学有关。

关键词: 糖尿病/药物疗法,  小檗碱/药理学,  小檗碱/投药和剂量,  胰高血糖素样肽1/药物作用,  抗原,CD26/药物作用,  血糖/血液,  糖尿病,实验性 
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