期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 26, 期 4-5, 页码 641-646出版社
KARGER
DOI: 10.1159/000322331
关键词
Dual electrode voltage clamp; SGLT1; Intestine; Ussing chamber
资金
- Deutsche Forschungsgemeinschaft [GK 1302]
Glycogen synthase kinase 3 GSK3 beta participates in a wide variety of functions including regulation of glucose metabolism. It is ubiquitously expressed including epithelial tissues. However, whether GSK3 beta participates in the regulation of epithelial transport is not known. The present study thus explored whether GSK3 beta influences the Na+-coupled transport of glucose. To this end, SGLT1 was expressed in Xenopus oocytes with or without GSK3 beta and glucose-induced current (I-g) determined by dual electrode voltage clamp. In Xenopus oocytes expressing SGLT1 but not in water-injected oocytes glucose induced an inwardly directed I-g, which was significantly enhanced by coexpression of GSK3 beta. According to chemiluminescence and confocal microscopy, GSK3 beta increased the SGLT1 protein abundance in the oocyte cell membrane. To explore whether GSK3 beta sensitivity of SGLT1 participates in the regulation of electrogenic intestinal glucose transport, Ussing chamber experiments were performed in intestinal segments from gene-targeted knockin mice with mutated and thus PKB/SGK-resistant GSK3 alpha,beta (gsk3(KI)), in which the serine of the PKB/SGK phosphorylation site was replaced by alanine, and from wild type mice (gsk3(WT)). The glucose-induced current was significantly larger in gsk3(KI) than in gsk3(WT) mice. The present observations reveal a novel function of GSK3, i.e. the stimulation of Na+-coupled glucose transport. Copyright (C) 2010 S. Karger AG, Basel
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