Rafacho A, Roma L P, Taboga S R, Boschero A C, Bosqueiro J R
Department of Physiology and Biophysics, Institute of Biology, State University of Campinas (UNICAMP), Campinas, S.P, Brazil.
Can J Physiol Pharmacol. 2007 May;85(5):536-45. doi: 10.1139/y07-037.
Augmented glucose-stimulated insulin secretion (GSIS) is an adaptive mechanism exhibited by pancreatic islets from insulin-resistant animal models. Gap junction proteins have been proposed to contribute to islet function. As such, we investigated the expression of connexin 36 (Cx36), connexin 43 (Cx43), and the glucose transporter Glut2 at mRNA and protein levels in pancreatic islets of dexamethasone (DEX)-induced insulin-resistant rats. Study rats received daily injections of DEX (1 mg/kg body mass, i.p.) for 5 days, whereas control rats (CTL) received saline solution. DEX rats exhibited peripheral insulin resistance, as indicated by the significant postabsorptive insulin levels and by the constant rate for glucose disappearance (KITT). GSIS was significantly higher in DEX islets (1.8-fold in 16.7 mmol/L glucose vs. CTL, p < 0.05). A significant increase of 2.25-fold in islet area was observed in DEX vs. CTL islets (p < 0.05). Cx36 mRNA expression was significantly augmented, Cx43 diminished, and Glut2 mRNA was unaltered in islets of DEX vs. CTL (p < 0.05). Cx36 protein expression was 1.6-fold higher than that of CTL islets (p < 0.05). Glut2 protein expression was unaltered and Cx43 was not detected at the protein level. We conclude that DEX-induced insulin resistance is accompanied by increased GSIS and this may be associated with increase of Cx36 protein expression.
葡萄糖刺激的胰岛素分泌增强（GSIS）是胰岛素抵抗动物模型的胰岛所表现出的一种适应性机制。间隙连接蛋白被认为对胰岛功能有贡献。因此，我们研究了地塞米松（DEX）诱导的胰岛素抵抗大鼠胰岛中连接蛋白36（Cx36）、连接蛋白43（Cx43）和葡萄糖转运蛋白Glut2在mRNA和蛋白质水平的表达。研究大鼠每天腹腔注射DEX（1mg/kg体重），持续5天，而对照大鼠（CTL）注射生理盐水。DEX大鼠表现出外周胰岛素抵抗，这通过空腹后胰岛素水平显著升高以及葡萄糖消失率（KITT）恒定来表明。DEX胰岛中的GSIS显著更高（在16.7mmol/L葡萄糖条件下是CTL的1.8倍，p<0.05）。与CTL胰岛相比，DEX胰岛的胰岛面积显著增加了2.25倍（p<0.05）。与CTL相比，DEX胰岛中Cx36 mRNA表达显著增加，Cx43减少，Glut2 mRNA未改变（p<0.05）。Cx36蛋白表达比CTL胰岛高1.6倍（p<0.05）。Glut2蛋白表达未改变，且在蛋白质水平未检测到Cx43。我们得出结论，DEX诱导的胰岛素抵抗伴随着GSIS增加，这可能与Cx36蛋白表达增加有关。
