Ziv E, Kalman R, Hershkop K, Barash V, Shafrir E, Bar-On H
Diabetes Research Unit, Hadassah University Hospital, Jerusalem, Israel.
Diabetologia. 1996 Nov;39(11):1269-75. doi: 10.1007/s001250050569.
The desert gerbil Psammomys obesus ("sand rat"), a model of nutritionally induced insulin resistance and non-insulin-dependent diabetes mellitus, was treated after weaning with exogenous insulin implants in the normoglycaemic, normoinsulinaemic state. Albino rats matched for weight and age served as high energy diet adjusted reference animals. Insulin administration, elevating the serum insulin to 6000 pmol/l resulted in only a mild reduction in blood glucose levels in Psammomys, but caused a severe, often fatal hypoglycaemia in the albino rats. The hepatic response to insulin-induced hypoglycaemia in rats involved a significant loss in glycogen and suppression of phosphoenolpyruvate carboxykinase (PEPCK) activity. In Psammomys under similar hyperinsulinaemia no appreciable changes in liver glycogen and PEPCK activity were evident, indicating that blood glucose was replenished by continuing gluconeogenesis. Euglycaemic, hyperinsulinaemic clamp caused a complete shut-down of hepatic glucose production in albino rats. However, in both diabetes-prone and diabetes-resistant Psammomys lines, mean hepatic glucose production was reduced by only 62 to 53% respectively, despite longer lasting and higher levels of hyperinsulinaemia. These results indicate that Psammomys is characterized by muscle and liver insulin resistance prior to diet-induced hyperglycaemia and hyperinsulinaemia. This is assumed to be a species feature of Psammomys, exemplifying a metabolic adjustment to survival in conditions of food scarcity of both animal and human populations. It may reflect a propensity to insulin resistance and hyperglycaemia in population groups exposed to affluent nutrition.
沙漠沙鼠（Psammomys obesus，即“沙大鼠”）是营养诱导性胰岛素抵抗和非胰岛素依赖型糖尿病的模型，在断奶后于血糖正常、胰岛素正常的状态下接受外源性胰岛素植入治疗。体重和年龄匹配的白化大鼠作为高能量饮食调整参考动物。给予胰岛素使沙鼠血清胰岛素水平升至6000 pmol/l，仅导致血糖水平轻度降低，但却使白化大鼠发生严重的、常为致命性的低血糖。大鼠肝脏对胰岛素诱导的低血糖反应包括糖原显著减少以及磷酸烯醇式丙酮酸羧激酶（PEPCK）活性受抑制。在类似的高胰岛素血症状态下，沙鼠肝脏糖原和PEPCK活性无明显变化，表明血糖是通过持续的糖异生得以补充。正常血糖、高胰岛素血症钳夹试验使白化大鼠肝脏葡萄糖生成完全停止。然而，在易患糖尿病和抗糖尿病的沙鼠品系中，尽管高胰岛素血症持续时间更长、水平更高，但平均肝脏葡萄糖生成分别仅降低62%至53%。这些结果表明，沙鼠在饮食诱导的高血糖和高胰岛素血症之前即具有肌肉和肝脏胰岛素抵抗。这被认为是沙鼠的一种物种特征，体现了动物和人类群体在食物匮乏条件下为生存而进行的代谢调整。它可能反映了在营养丰富人群中存在胰岛素抵抗和高血糖的倾向。
