Rexhepaj Rexhep, Dërmaku-Sopjani Miribane, Gehring Eva-Maria, Sopjani Mentor, Kempe Daniela S, Föller Michael, Lang Florian
Department of Physiology, University of Tübingen, Tübingen, Germany.
Cell Physiol Biochem. 2010;26(4-5):641-6. doi: 10.1159/000322331. Epub 2010 Oct 29.
Glycogen synthase kinase 3 GSK3β participates in a wide variety of functions including regulation of glucose metabolism. It is ubiquitously expressed including epithelial tissues. However, whether GSK3β participates in the regulation of epithelial transport is not known. The present study thus explored whether GSK3β influences the Na(+)-coupled transport of glucose. To this end, SGLT1 was expressed in Xenopus oocytes with or without GSK3β 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 GSK3β. According to chemiluminescence and confocal microscopy, GSK3β increased the SGLT1 protein abundance in the oocyte cell membrane. To explore whether GSK3β 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 GSK3α,β (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.
糖原合酶激酶3（GSK3β）参与多种功能，包括调节葡萄糖代谢。它在包括上皮组织在内的各种组织中广泛表达。然而，GSK3β是否参与上皮转运的调节尚不清楚。因此，本研究探讨了GSK3β是否影响葡萄糖的钠偶联转运。为此，将钠葡萄糖协同转运蛋白1（SGLT1）在有或没有GSK3β的非洲爪蟾卵母细胞中表达，并通过双电极电压钳测定葡萄糖诱导的电流（I(g)）。在表达SGLT1的非洲爪蟾卵母细胞中，而不是在注射水的卵母细胞中，葡萄糖诱导内向I(g)，GSK3β的共表达可显著增强该电流。根据化学发光和共聚焦显微镜观察，GSK3β增加了卵母细胞膜中SGLT1蛋白的丰度。为了探究SGLT1对GSK3β的敏感性是否参与电生性肠道葡萄糖转运的调节，对基因靶向敲入小鼠（gsk3(KI)）和野生型小鼠（gsk3(WT)）的肠段进行了Ussing chamber实验。gsk3(KI)小鼠的PKB/SGK磷酸化位点的丝氨酸被丙氨酸取代，从而对PKB/SGK具有抗性。gsk3(KI)小鼠中葡萄糖诱导的电流明显大于gsk3(WT)小鼠。本研究结果揭示了GSK3的一种新功能，即刺激钠偶联葡萄糖转运。
