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[Urotensin II inhibits glucokinase expression and glucose induced insulin secretion.] [Ariticle in Chinese]

LIU Fang, ZHU Yi-Chun^*

Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Abstract

The purpose of the present study is to investigate the effects of urotensin II (UII) on insulin secretion in islet β cells and theunderlying mechanism. Glucose tolerance test was performed in Wistar rats to evaluate the effect of UII on the levels of plasma glucoseand insulin. Static incubation experiment was employed to investigate the effect of UII on glucose-induced insulin secretion (GIIS) inβTC-6 cells. After the incubation, insulin content and mRNA level in βTC-6 cells were analyzed. Finally, Western blot was used to findout if UII could change the expression levels of pancreatic duodenal homeobox-1 (PDX-1) and glucokinase (GCK). It was observed thatintravenous administration of UII (30, 300 nmol/kg) resulted in a significant decrease in insulin level 15 min after glucose load, andinduced an obvious increase in plasma glucose 90 min after the load. In vitro, two hours of UII incubation inhibited GIIS in βTC-6 cellswithout affecting insulin content and mRNA levels. The inhibitory effect of UII was blocked by UII receptor antagonist (urantide), andpartially blunted by protein kinase C (PKC) inhibitor (chelerythrine) and somatostatin receptor antagonist (cyclosomatostatin).Moreover, we found that GCK protein level was significantly reduced by UII, while PDX-1, a key regulator of insulin gene transcriptionin β cells, was not affected. These results suggest that UII-induced inhibition of GIIS in βTC-6 cells are mediated by UII receptorand PKC pathway, as well as somatostatin receptor which could be activated by high dose of UII. The inhibitory effect of UII oninsulin secretion is rather associated with a suppression of GCK expression than a regulation on PDX-1 expression.

Key words: urotensin II; glucose tolerance; insulin; protein kinase C; glucokinase; receptors, somatostatin

Received: 2009-12-22　　Accepted: 2010-03-08

Corresponding author: 朱依纯　　E-mail: yczhu@shmu.edu.cn

Citing This Article：

LIU Fang, ZHU Yi-Chun. [Urotensin II inhibits glucokinase expression and glucose induced insulin secretion.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (2): 129-136 (in Chinese with English abstract).