Cannabinoids inhibit insulin secretion and cytosolic Ca2+ oscillation in islet β-cells via CB1 receptors

被引:101
作者
Nakata, Masanori [1 ]
Yada, Toshihiko [1 ]
机构
[1] Jichi Med Sch, Sch Med, Div Integrat Physiol, Dept Physiol, Minami Kawachi, Tochigi 32904, Japan
基金
日本学术振兴会;
关键词
cannabinoids; CB1; receptor; insulin; pancreatic beta-cell; calcium oscillation;
D O I
10.1016/j.regpep.2007.08.009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Obesity is the main risk factor for the development of metabolic syndrome. Endogenous cannabinoids act on the cannabinoid type 1 (CB1) receptor, a GPCR, and stimulate appetite via central and peripheral actions, while blockade of CB1 receptor reduces body weight in humans. In this study, we aimed to explore a role of the peripheral endocannabinoid system in insulin secretion, which could be important in the metabolic effects of the cannabinoid-CB1 system. We found that mRNA for CB1 receptor, but not CB2 receptor, was expressed in mouse pancreatic islets using RT-PCR. Immunohistochemical study revealed that CB1 receptor was expressed in beta-cells. Furthermore, anandamide and a CB1 agonist, arachidonylcyclopropylamide (ACPA), inhibited glucose-induced insulin secretion from mouse pancreatic islets. Both anandamide and ACPA inhibited glucose-induced cytosolic Ca2+ oscillation in mouse pancreatic beta-cells. These results demonstrate a novel peripheral action of cannabinoids to inhibit insulin secretion via CB1 receptors. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:49 / 53
页数:5
相关论文
共 21 条
[1]   The cannabinoid CB1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells [J].
Bensaid, M ;
Gary-Bobo, M ;
Esclangon, A ;
Maffrand, JP ;
Le Fur, G ;
Oury-Donat, F ;
Soubrié, P .
MOLECULAR PHARMACOLOGY, 2003, 63 (04) :908-914
[2]   Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle [J].
Bonz, A ;
Laser, M ;
Küllmer, S ;
Kniesch, S ;
Babin-Ebell, J ;
Popp, V ;
Ertl, G ;
Wagner, JA .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2003, 41 (04) :657-664
[3]  
Cota D, 2003, J CLIN INVEST, V112, P423, DOI [10.1172/JCI200317725, 10.1172/JCI17725]
[4]   Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia [J].
Despres, JP ;
Golay, A ;
Sjostrom, L .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (20) :2121-2134
[5]   Leptin-regulated endocannabinoids are involved in maintaining food intake [J].
Di Marzo, V ;
Goparaju, SK ;
Wang, L ;
Liu, J ;
Bátkai, S ;
Járai, Z ;
Fezza, F ;
Miura, GI ;
Palmiter, RD ;
Sugiura, T ;
Kunos, G .
NATURE, 2001, 410 (6830) :822-825
[6]   Activation of the peripheral endocannabinoid system in human obesity [J].
Engeli, S ;
Böhnke, J ;
Feldpausch, M ;
Gorzelniak, K ;
Janke, J ;
Bátkai, S ;
Pacher, P ;
Harvey-White, J ;
Luft, FC ;
Sharma, AM ;
Jordan, J .
DIABETES, 2005, 54 (10) :2838-2843
[7]  
GILON P, 1993, J BIOL CHEM, V268, P22265
[8]  
Giuffrida A, 2001, J PHARMACOL EXP THER, V298, P7
[9]   HU-308:: A specific agonist for CB2, a peripheral cannabinoid receptor [J].
Hanus, L ;
Breuer, A ;
Tchilibon, S ;
Shiloah, S ;
Goldenberg, D ;
Horowitz, M ;
Pertwee, RG ;
Ross, RA ;
Mechoulam, R ;
Fride, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (25) :14228-14233
[10]   CANNABINOID RECEPTOR LOCALIZATION IN BRAIN [J].
HERKENHAM, M ;
LYNN, AB ;
LITTLE, MD ;
JOHNSON, MR ;
MELVIN, LS ;
DECOSTA, BR ;
RICE, KC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (05) :1932-1936