SEVERE DIABETES INDUCED IN SUBTOTALLY DEPANCREATIZED DOGS BY SUSTAINED HYPERGLYCEMIA
SEVERE DIABETES INDUCED IN SUBTOTALLY DEPANCREATIZED DOGS BY SUSTAINED HYPERGLYCEMIA
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DOI：
10.2337/diabetes.37.5.600
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发表时间：
1988-05-01
期刊：
影响因子：
7.7
通讯作者：
UNGER, RH
中科院分区：
文献类型：
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作者：
IMAMURA, T;KOFFLER, M;UNGER, RH
血糖水平的慢性钳制250 mg/dl，在4只部分去胰但先前未患糖尿病的狗中，在2周内出现持续的高血糖症和≤500克/天，酮尿症，体重减轻。四只狗中的三只需要每天注射胰岛素来控制这些分解代谢表现。在停止静脉输注葡萄糖后的39-69天观察期间，没有证据表明重度糖尿病状态自发改善。静脉葡萄糖耐量受损、胰岛素对葡萄糖和精氨酸的反应丧失、空腹高胰高血糖素血症、胰高血糖素对精氨酸的反应过度以及对胰岛素的敏感性显著降低是所有糖尿病犬的特征。内分泌胰腺的形态学分析显示，与几个月前切除的自身胰腺的胰岛相比，高血糖犬的可识别胰岛的数量和大小显著减少，与8只未进行慢性高血糖钳夹的次全胰腺切除对照犬的胰腺残余物的胰岛相比。高血糖犬胰岛数量和大小的减少主要是含胰岛素细胞耗竭的结果，与长期四氧嘧啶诱导的糖尿病犬相似。在8只对照犬中，在193-296天的随访期间未出现糖尿病的临床证据。在该组中，没有证据表明静脉内葡萄糖耐量降低，胰岛素对葡萄糖或精氨酸的反应降低，或通过急性高胰岛素高血糖钳夹测定的胰岛素敏感性降低。胰岛的数量和大小以及β的数量-这些狗的胰腺残留物中的细胞与切除的胰腺段中的细胞在形态上没有差异。我们的结论是，在次全胰腺切除，但非糖尿病的狗，维持恒定的高血糖。通过静脉内葡萄糖输注250 mg/dl会导致严重的、持续的、通常需要胰岛素的糖尿病状态，在没有高血糖症的情况下不会发生。
Chronic clamping of plasma glucose levels at .gtoreq. 250 mg/dl in four partially depancreatized but previously nondiabetic dogs was followed within 2 wk by persistent hyperglycemia and glycosuria of .ltoreq. 500 g/day, ketonuria, and weight loss. Three of the four dogs required daily insulin injections to control these catabolic manifestations. There was no evidence of spontaneous improvement of the severe diabetic state during the 39-69 days of observation after discontinuation of intravenous glucose infusion. Impairment of intravenous glucose tolerance, loss of the insulin response to glucose and arginine, fasting hyperglucagonemia, exaggerated glucagon responsiveness to arginine, and a significant reduction in sensitivity to insulin were characteristic of all diabetic dogs. Morphometric analysis of the endocrine pancreas revealed a profound reduction in the number and size of identifiable islets of the hyperglycemic dogs compared with islets from their own pancreases resected months earlier and with those from pancreatic remnants of eight subtotally depancreatized control dogs that had not been subjected to chronic hyperglycemic clamping. The reduction in number and size of islets of the hyperglycemic dogs was largely the consequence of depletion of insulin-containing cells and was similar to that of dogs with long-standing alloxan-induced diabetes. In the eight control dogs, clinical evidence of diabetes did not develop during a follow-up period of 193-296 days. In this group, there was no evidence of diminution of intravenous glucose tolerance, of the insulin response to glucose or arginine, or of insulin sensitivity as determined by an acute hyperinsulinemic hyperglycemic clamp. The number and size of islets and number of .beta.-cells in pancreatic remnants from these dogs did not differ morphometrically from those of the pancreatic segment that had been resected. We conclude that in subtotally depancreatized but nondiabetic dogs, maintenance of constant hyperglycemia of .gtoreq. 250 mg/dl by means of intravenous glucose infusion causes a severe, persistent, and often insulin-requiring diabetic state that does not occur in the absence of the hyperglycemia.