Valera A, Pujol A, Pelegrin M, Bosch F
Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain.
Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9151-4. doi: 10.1073/pnas.91.19.9151.
An increase in hepatic gluconeogenesis is believed to be an important factor responsible for the fasting hyperglycemia detected in patients with non-insulin-dependent diabetes mellitus (NIDDM). Phosphoenolpyruvate carboxykinase (GTP) (PEPCK; EC 4.1.1.32) is a regulatory enzyme of gluconeogenesis. To study the role of the expression of PEPCK gene in the development of NIDDM, we have produced lines of transgenic mice expressing a PEPCK minigene under control of its own promoter. Transgenic mice were hyperglycemic and had higher serum insulin concentrations. In addition, alterations in liver glycogen content and muscle glucose transporter GLUT-4 gene expression were detected. The overexpression of the PEPCK gene led to an increase in glucose production from pyruvate in hepatocytes in primary culture. When intraperitoneal glucose tolerance tests were performed, blood glucose levels were higher than those detected in normal mice. This animal model shows that primary alterations in the rate of liver glucose production may induce insulin resistance and NIDDM.
肝糖异生增加被认为是导致非胰岛素依赖型糖尿病（NIDDM）患者空腹高血糖的一个重要因素。磷酸烯醇式丙酮酸羧激酶（GTP）（PEPCK；EC 4.1.1.32）是糖异生的一种调节酶。为了研究PEPCK基因表达在NIDDM发病过程中的作用，我们构建了在其自身启动子控制下表达PEPCK小基因的转基因小鼠品系。转基因小鼠出现高血糖，血清胰岛素浓度更高。此外，还检测到肝糖原含量和肌肉葡萄糖转运蛋白GLUT-4基因表达的改变。PEPCK基因的过表达导致原代培养的肝细胞中丙酮酸生成葡萄糖增加。进行腹腔葡萄糖耐量试验时，血糖水平高于正常小鼠。这个动物模型表明，肝脏葡萄糖生成速率的原发性改变可能会诱导胰岛素抵抗和NIDDM。
