Liang Y, Bonner-Weir S, Wu Y J, Berdanier C D, Berner D K, Efrat S, Matschinsky F M
Department of Biochemistry and Biophysics, University of Pennyslvania, Philadelphia 19104.
J Clin Invest. 1994 Jun;93(6):2473-81. doi: 10.1172/JCI117256.
The present study evaluated the involvement of glucose transport and phosphorylation in glucose-stimulated insulin release from pancreatic islets. Using quantitative histochemical techniques, we investigated basal islet glucose content, islet glucose uptake in situ during acute extreme experimental hyperglycemia, and islet glucokinase activity in several animal models of diabetes and obesity. The basal islet glucose content in anaesthetized diabetic or obese rodents was either the same or higher than that in their relevant controls. The rate of glucose uptake of islet tissue in these animals after an i.v. glucose injection was different. The db+/db+ mouse and the obese Zucker rat exhibited significantly reduced islet glucose uptake rates. RIP-cHras transgenic mice, BHE/cdb rats and partially pancreatectomized rats showed normal islet glucose uptake rates. The activity of islet glucokinase was increased to a different degree related to the blood glucose level. All five animal models of diabetes or obesity exhibited either a delay or a reduction of insulin release in response to supra maximal glucose stimulation. Our results indicate that the impairment of glucose-induced insulin release in diabetes is not consistently associated with a reduction of islet glucose uptake nor a change of glucokinase activity.
本研究评估了葡萄糖转运和磷酸化在葡萄糖刺激的胰岛胰岛素释放中的作用。我们使用定量组织化学技术，研究了几种糖尿病和肥胖动物模型中胰岛的基础葡萄糖含量、急性极端实验性高血糖期间原位胰岛葡萄糖摄取以及胰岛葡萄糖激酶活性。麻醉的糖尿病或肥胖啮齿动物的基础胰岛葡萄糖含量与相应对照组相同或更高。静脉注射葡萄糖后，这些动物的胰岛组织葡萄糖摄取率有所不同。db+/db+小鼠和肥胖的 Zucker 大鼠的胰岛葡萄糖摄取率显著降低。RIP-cHras 转基因小鼠、BHE/cdb 大鼠和部分胰腺切除的大鼠的胰岛葡萄糖摄取率正常。胰岛葡萄糖激酶活性与血糖水平呈不同程度的升高。所有五种糖尿病或肥胖动物模型在超最大葡萄糖刺激下均表现出胰岛素释放延迟或减少。我们的结果表明，糖尿病中葡萄糖诱导的胰岛素释放受损并不总是与胰岛葡萄糖摄取减少或葡萄糖激酶活性变化相关。
