Boozer C N, Mayer J
Diabetologia. 1976 May;12(2):181-7. doi: 10.1007/BF00428986.
Primary hypersecretion of insulin has been suggested as one possibility for the genetic fault of ob/ob mice. To test this hypothesis, streptozotocin (SZO) was used to reduce permanently insulin secretion in young lean and obese mice. After establishment of hyperglycaemia and weight reduction in treated obese mice (obese-SZO), daily insulin replacment was begun in some (obese-SZO-Ins). Obese-SZO mice maintained insulin levels and body weights similar to lean controls, though they were shorter and fatter, while food intake and blood sugar levels exceeded lean values. Obese-SZO-Ins mice with reduced islet hyperplasia, but great insulin resistance, gained more weight than obese-SZO mice; had high serum insulin and controlled blood glucose; and exhibited hyperphagia. These results suggest that primary hypersecretion of insulin cannot be the genetic defect, as ob/ob mice are hyperphagic, hyperglycaemic, insulin resistant, and "obese" even when insulin levels are restricted.
胰岛素原发性分泌过多已被认为是ob/ob小鼠基因缺陷的一种可能性。为了验证这一假设，使用链脲佐菌素（SZO）永久性降低年轻瘦小鼠和肥胖小鼠的胰岛素分泌。在处理后的肥胖小鼠（肥胖-SZO）中建立高血糖和体重减轻后，部分小鼠开始每日胰岛素替代治疗（肥胖-SZO-Ins）。肥胖-SZO小鼠的胰岛素水平和体重与瘦对照相似，尽管它们更矮更胖，而食物摄入量和血糖水平超过瘦对照值。胰岛增生减少但胰岛素抵抗严重的肥胖-SZO-Ins小鼠比肥胖-SZO小鼠体重增加更多；血清胰岛素水平高且血糖得到控制；并表现出食欲亢进。这些结果表明，胰岛素原发性分泌过多不可能是基因缺陷，因为即使胰岛素水平受到限制，ob/ob小鼠仍会出现食欲亢进、高血糖、胰岛素抵抗和“肥胖”。
