Veroni M C, Proietto J, Larkins R G
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.
Diabetes. 1991 Nov;40(11):1480-7. doi: 10.2337/diab.40.11.1480.
The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is not known. Hyperglycemia is due to increased hepatic glucose production (HGP), decreased glucose uptake, and impaired insulin secretion. It is unknown if these defects are coinherited or if one precedes and causes the others. The aim of this study was to determine the earliest defects in the evolution of the syndrome in the New Zealand obese (NZO) mouse, a polygenic model of NIDDM. NZO and control NZC mice were studied at 4-5 and 20 wk of age. Glucose turnover and glucose uptake in individual tissues were measured basally and during a hyperinsulinemic clamp. First-phase insulin secretion was measured after an intravenous glucose load. HGP was higher in the NZO mice both basally and during the clamp at both ages. At 4-5 wk of age, there was evidence of insulin insensitivity in brown adipose tissue, soleus, diaphragm, red quadriceps, and red gastrocnemius but not in heart, white quadriceps, and white gastrocnemius. In 20-wk-old mice, insulin responsiveness was decreased in white and brown adipose tissue and soleus muscle but not in heart, diaphragm, red and white quadriceps, and red and white gastrocnemius. First-phase insulin secretion (percentage rise above basal) 3 min after the glucose bolus was impaired in NZO mice at both ages. We conclude that hepatic glucose overproduction, brown adipose tissue and skeletal muscle insulin resistance, and impaired first-phase insulin secretion are all early abnormalities in the NZO mouse.
非胰岛素依赖型糖尿病（NIDDM）的病因尚不清楚。高血糖是由于肝脏葡萄糖生成增加（HGP）、葡萄糖摄取减少和胰岛素分泌受损所致。这些缺陷是共同遗传的，还是一个先出现并导致其他缺陷，目前尚不清楚。本研究的目的是确定新西兰肥胖（NZO）小鼠（一种NIDDM的多基因模型）综合征演变过程中最早出现的缺陷。对4-5周龄和20周龄的NZO小鼠和对照NZC小鼠进行了研究。在基础状态和高胰岛素钳夹期间测量了各个组织中的葡萄糖周转率和葡萄糖摄取。静脉注射葡萄糖负荷后测量第一相胰岛素分泌。在两个年龄阶段，NZO小鼠基础状态和钳夹期间的HGP均较高。在4-5周龄时，棕色脂肪组织、比目鱼肌、膈肌、红色股四头肌和红色腓肠肌存在胰岛素不敏感的证据，但心脏、白色股四头肌和白色腓肠肌不存在。在20周龄的小鼠中，白色和棕色脂肪组织以及比目鱼肌的胰岛素反应性降低，但心脏、膈肌、红色和白色股四头肌以及红色和白色腓肠肌没有降低。在两个年龄阶段，NZO小鼠在葡萄糖推注后3分钟的第一相胰岛素分泌（高于基础值的百分比升高）均受损。我们得出结论，肝脏葡萄糖过度生成、棕色脂肪组织和骨骼肌胰岛素抵抗以及第一相胰岛素分泌受损都是NZO小鼠早期出现的异常情况。
