GLP-1 Inhibits and Adrenaline Stimulates Glucagon Release by Differential Modulation of N- and L-Type Ca2+ Channel-Dependent Exocytosis

被引：221

作者：

De Marinis, Yang Z. ^{[1
]}

Salehi, Albert ^{[1
]}

Ward, Caroline E. ^{[2
]}

Zhang, Quan ^{[2
]}

Abdulkader, Fernando ^{[2
,5
]}

Bengtsson, Martin ^{[2
]}

Braha, Orit ^{[2
]}

Braun, Matthias ^{[2
]}

Ramracheya, Reshma ^{[2
]}

Amisten, Stefan ^{[2
]}

Habib, Abdella M. ^{[3
]}

Moritoh, Yusuke ^{[2
]}

Zhang, Enming ^{[1
]}

Reimann, Frank ^{[3
]}

Rosengren, Anders H. ^{[1
]}

Shibasaki, Tadao ^{[4
]}

Gribble, Fiona ^{[3
]}

Renstrom, Erik ^{[1
]}

Seino, Susumu ^{[4
]}

Eliasson, Lena ^{[1
]}

Rorsman, Patrik ^{[2
]}

机构：

[1] Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Clin Res Ctr, SE-20502 Malmo, Sweden

[2] Univ Oxford, Oxford Ctr Diabet Endocnnol & Metab, Oxford OX3 7LJ, England

[3] Univ Cambridge, Cambridge Inst Med Res, Addenbrookes Hosp, Cambridge CB2 OXY, England

[4] Kobe Univ, Grad Sch Med, Div Cellular & Mol Med, Dept Physiol & Cell Biol,Chou Ku, Kobe, Hyogo 6500017, Japan

[5] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-0550800 Sao Paulo, Brazil

来源：

CELL METABOLISM | 2010年 / 11卷 / 06期

基金：

日本科学技术振兴机构; 英国惠康基金; 瑞典研究理事会;

关键词：

ALPHA-CELLS; MOUSE; GLUCOSE; INSULIN; SECRETION; RAT; EXPRESSION; RECEPTOR; CURRENTS;

D O I：

10.1016/j.cmet.2010.04.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Glucagon secretion is inhibited by glucagon-like peptide-1 (GLP-1) and stimulated by adrenaline. These opposing effects on glucagon secretion are mimicked by low (1-10 nM) and high (10 mu M) concentrations of forskolin, respectively. The expression of GLP-1 receptors in a cells is <0.2% of that in beta cells. The GLP-1-induced suppression of glucagon secretion is PKA dependent, is glucose independent, and does not involve paracrine effects mediated by insulin or somatostatin. GLP-1 is without much effect on a cell electrical activity but selectively inhibits N-type Ca2+ channels and exocytosis. Adrenaline stimulates a cell electrical activity, increases [Ca2+] enhances L-type Ca2+ channel activity, and accelerates exocytosis. The stimulatory effect is partially PKA independent and reduced in Epac2-deficient islets. We propose that GLP-1 inhibits glucagon secretion by PKA-dependent inhibition of the N-type Ca2+ channels via a small increase in intracellular cAMP ([cAMP]). Adrenaline stimulates L-type Ca2+ channel-dependent exocytosis by activation of the low-affinity cAMP sensor Epac2 via a large increase in [cAMP],.

引用

页码：543 / 553

页数：11

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