Kaiser Nurit, Nesher Rafael, Donath Marc Y, Fraenkel Merav, Behar Vered, Magnan Christophe, Ktorza Alain, Cerasi Erol, Leibowitz Gil
Endocrinology and Metabolism Service, Department of Internal Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Diabetes. 2005 Dec;54 Suppl 2:S137-44. doi: 10.2337/diabetes.54.suppl_2.s137.
Type 2 diabetes is characterized by insulin resistance and progressive beta-cell failure. Deficient insulin secretion, with increased proportions of insulin precursor molecules, is a common feature of type 2 diabetes; this could result from inappropriate beta-cell function and/or reduced beta-cell mass. Most studies using tissues from diabetic patients are retrospective, providing only limited information on the relative contribution of beta-cell dysfunction versus decreased beta-cell mass to the "beta-cell failure" of type 2 diabetes. The gerbil Psammomys obesus is a good model to address questions related to the role of insulin resistance and beta-cell failure in nutritionally induced diabetes. Upon a change from its natural low-calorie diet to the calorie-rich laboratory food, P. obesus develops moderate obesity associated with postprandial hyperglycemia. Continued dietary load, superimposed on its innate insulin resistance, results in depletion of pancreatic insulin stores, with increased proportions of insulin precursor molecules in the pancreas and the blood. Inadequate response of the preproinsulin gene to the increased insulin needs is an important cause of diabetes progression. Changes in beta-cell mass do not correlate with pancreatic insulin stores and are unlikely to play a role in disease initiation and progression. The major culprit is the inappropriate insulin production with depletion of insulin stores as a consequence. Similar mechanisms could operate during the evolution of type 2 diabetes in humans.
2型糖尿病的特征是胰岛素抵抗和进行性β细胞功能衰竭。胰岛素分泌不足，胰岛素前体分子比例增加，是2型糖尿病的常见特征；这可能是由于β细胞功能异常和/或β细胞数量减少所致。大多数使用糖尿病患者组织的研究都是回顾性的，仅提供了关于β细胞功能障碍与β细胞数量减少对2型糖尿病“β细胞功能衰竭”的相对贡献的有限信息。沙鼠肥胖症是研究胰岛素抵抗和β细胞功能衰竭在营养性诱导糖尿病中作用相关问题的良好模型。从其天然的低热量饮食转变为高热量的实验室食物后，肥胖症沙鼠会出现与餐后高血糖相关的中度肥胖。持续的饮食负荷，叠加其先天性胰岛素抵抗，导致胰腺胰岛素储备耗竭，胰腺和血液中胰岛素前体分子比例增加。胰岛素原基因对增加的胰岛素需求反应不足是糖尿病进展的重要原因。β细胞数量的变化与胰腺胰岛素储备无关，不太可能在疾病的发生和发展中起作用。主要原因是胰岛素产生不当，导致胰岛素储备耗竭。类似的机制可能在人类2型糖尿病的发展过程中起作用。
