Amrani A, Durant S, Throsby M, Coulaud J, Dardenne M, Homo-Delarche F
Centre National de la Recherche Scientifique Unité de Recherches Associée 1461-Université Paris V, Hôpital Necker, France.
Endocrinology. 1998 Mar;139(3):1115-24. doi: 10.1210/endo.139.3.5823.
Because few data were available on glucose homeostasis at the early prediabetic stage in the nonobese diabetic (NOD) mouse, we investigated glycemia, insulinemia, and pancreatic insulin content under basal conditions in both sexes of 4-, 6-, and 8-week-old fed NOD mice, compared with sex- and age-matched fed C57BL/6 mice. We also investigated glucose tolerance in both sexes of fasting 8-week-old NOD and C57BL/6 mice. The main results obtained under basal fed conditions, when comparing both strains, were lower glycemia and higher insulinemia in NOD females at all ages investigated and in NOD males (particularly at 6 weeks of age). Glucose tolerance tests showed that: 1) the blood glucose response to 1 g/kg i.p. glucose was less sustained in both sexes of 8-week-old NOD mice than in their control counterparts; 2) the blood insulin response to glucose (1 g/kg i.p.) appeared earlier in both sexes of NOD mice than in sex-matched C57BL/6 mice; 3) an unusual sexual dimorphism existed in NOD mice, compared with controls, with females secreting, in response to glucose, twice as much insulin as males; 4) dose-response studies (1-6 g/kg glucose) confirmed the lower increase in blood glucose levels in both sexes of NOD mice and their unusual sexual dimorphism in insulin secretion; and 5) glucose tolerance tests in 4- to 8-week-old NOD mice showed that although the sexual dimorphism in insulin secretion was not observed in 4-week-old mice, it was particularly striking at 6 weeks of age. Taken together, these results suggest that beta-cell hyperactivity exists in the NOD mouse at the early prediabetic stage, especially in NOD females.
由于关于非肥胖糖尿病（NOD）小鼠糖尿病前期早期阶段葡萄糖稳态的数据很少，我们研究了4周、6周和8周龄喂食的NOD小鼠两性在基础条件下的血糖、胰岛素血症和胰腺胰岛素含量，并与性别和年龄匹配的喂食C57BL/6小鼠进行比较。我们还研究了禁食8周龄NOD和C57BL/6小鼠两性的葡萄糖耐量。在基础喂食条件下比较两种品系时获得的主要结果是，在所有研究年龄的NOD雌性小鼠和NOD雄性小鼠（特别是6周龄时）中，血糖较低，胰岛素血症较高。葡萄糖耐量试验表明：1）8周龄NOD小鼠两性对1 g/kg腹腔注射葡萄糖的血糖反应持续时间比对照小鼠短；2）NOD小鼠两性对葡萄糖（1 g/kg腹腔注射）的血液胰岛素反应比性别匹配的C57BL/6小鼠出现得更早；3）与对照相比，NOD小鼠存在不寻常的性别二态性，雌性对葡萄糖的反应分泌的胰岛素是雄性的两倍；4）剂量反应研究（1 - 6 g/kg葡萄糖）证实了NOD小鼠两性血糖水平升高较低及其胰岛素分泌的不寻常性别二态性；5）4至8周龄NOD小鼠的葡萄糖耐量试验表明，虽然4周龄小鼠未观察到胰岛素分泌的性别二态性，但在6周龄时尤为明显。综上所述，这些结果表明，在糖尿病前期早期阶段，NOD小鼠存在β细胞功能亢进，尤其是在NOD雌性小鼠中。
