Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice

被引：156

作者：

Colsoul, Barbara ^{[1
]}

Schraenen, Anica ^{[2
]}

Lemaire, Katleen ^{[2
]}

Quintens, Roel ^{[2
]}

Van Lommel, Leentje ^{[2
]}

Segal, Andrei ^{[1
]}

Owsianik, Grzegorz ^{[1
]}

Talavera, Karel ^{[1
]}

Voets, Thomas ^{[1
]}

Margolskee, Robert F. ^{[3
]}

Kokrashvili, Zaza ^{[3
]}

Gilon, Patrick ^{[4
]}

Nilius, Bernd ^{[1
]}

Schuit, Frans C. ^{[2
]}

Vennekens, Rudi ^{[1
]}

机构：

[1] Katholieke Univ Leuven, Dept Mol Cell Biol, Lab Ion Channel Res, B-3001 Heverlee, Belgium

[2] Katholieke Univ Leuven, Dept Mol Cell Biol, Gene Express Unit, B-3001 Heverlee, Belgium

[3] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA

[4] Univ Louvain, Fac Med, Unit Endocrinol & Metab, B-1000 Brussels, Belgium

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 11期

基金：

美国国家卫生研究院;

关键词：

Ca2+ signaling; insulin release; pancreatic beta-cells; transient receptor potential ion channels; glucose sensing; NONSELECTIVE CATION CHANNEL; TRP GENE FAMILY; BETA-CELL; INSULIN-SECRETION; INTRACELLULAR CALCIUM; ELECTRICAL-ACTIVITY; CYTOPLASMIC CA2+; RECEPTOR-CELLS; ION-CHANNEL; EXOCYTOSIS;

D O I：

10.1073/pnas.0913107107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glucose homeostasis is critically dependent on insulin release from pancreatic beta-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (Vm) and the cytosolic calcium level ([Ca2+](cyt)). We propose that TRPM5, a Ca2+-activated monovalent cation channel, is a positive regulator of glucose-induced insulin release. Immunofluorescence revealed expression of TRPM5 in pancreatic islets. A Ca2+-activated nonselective cation current with TRPM5-like properties is significantly reduced in Trpm(5-/-) cells. Ca2+-imaging and electrophysiological analysis show that glucose- induced oscillations of V-m and [Ca2+](cyt) have on average a reduced frequency in Trpm5(-/-)islets, specifically due to a lack of fast oscillations. As a consequence, glucose-induced insulin release from Trpm5(-/-) pancreatic islets is significantly reduced, resulting in an impaired glucose tolerance in Trpm5(-/-) mice.

引用

页码：5208 / 5213

页数：6

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