期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 423, 期 C, 页码 1-10出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2015.12.015
关键词
Adenylyl cyclase; cAMP; CB1; GLP-1; Incretin; Insulin secretion
资金
- Intramural Research Program of National Institute on Aging within the National Institutes of Health
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT Future [NRF-2012R1A1A1041352, NRF-2015R1A2A1A15054227]
- Ministry of Education [NRF-2009-0093826]
- National Research Foundation of Korea [2012R1A1A1041352, 2015R1A2A1A15054227, 2009-0093826] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The cannabinoid 1 receptor (CBI) is an important regulator of energy metabolism. Reports of in vivo and in vitro studies give conflicting results regarding its role in insulin secretion, possibly due to circulatory factors, such as incretins. We hypothesized that this receptor may be a regulator of the entero-insular axis. We found that despite lower food consumption and lower body weight postprandial GLP-1 plasma concentrations were increased in CB1(-/-) mice compared to CB1(+/+) mice administered a standard diet or high fat/sugar diet. Upon exogenous GLP-1 treatment, CB1(-/-) mice had increased glucose stimulated insulin secretion. In mouse insulinoma cells, cannabinoids reduced GLP-1R-mediated intracellular CAMP accumulation and subsequent insulin secretion. Importantly, such effects were also evident in human islets, and were prevented by pharmacologic blockade of CB1. Collectively, these findings suggest a novel mechanism in which endocannabinoids are negative modulators of incretin-mediated insulin secretion. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据