Karounos D G, Bryson J S, Cohen D A
Department of Internal Medicine, Veterans Administration Medical Center and University of Kentucky College of Medicine, Lexington, Kentucky 40536-0084, USA.
J Clin Invest. 1997 Sep 15;100(6):1344-8. doi: 10.1172/JCI119654.
The purpose of this study was to determine the relative importance of the metabolic effects of insulin for diabetes prevention by administering insulin or an inactive insulin analog by daily subcutaneous injections to prediabetic mice. A recombinant monomeric human insulin analog, which does not bind to the insulin receptor as a consequence of an alteration of a single amino acid at position 25 of the B chain, was shown to be equally effective at diabetes prevention as was intact insulin. In contrast to native insulin, the insulin analog did not cause hypoglycemia after subcutaneous injection. The insulin analog, however, protected young adult mice from diabetes, even when it was initiated after the onset of extensive lymphocytic infiltration of the islets. Thus, preventative therapy by daily subcutaneous injections of insulin does not require the hypoglycemic response, or binding to the insulin receptor to prevent the onset of type I diabetes.
本研究的目的是通过对糖尿病前期小鼠每日皮下注射胰岛素或无活性胰岛素类似物，来确定胰岛素的代谢作用对预防糖尿病的相对重要性。一种重组单体人胰岛素类似物，由于B链第25位的单个氨基酸发生改变而不与胰岛素受体结合，结果显示其在预防糖尿病方面与完整胰岛素同样有效。与天然胰岛素不同，该胰岛素类似物皮下注射后不会引起低血糖。然而，即使在胰岛广泛淋巴细胞浸润开始后才开始使用，该胰岛素类似物仍能保护年轻成年小鼠不患糖尿病。因此，每日皮下注射胰岛素进行预防性治疗并不需要低血糖反应，也不需要与胰岛素受体结合来预防I型糖尿病的发生。
