POST-GLUT-2 DEFECTS IN BETA-CELLS OF NON-INSULIN-DEPENDENT DIABETIC OBESE RATS
POST-GLUT-2 DEFECTS IN BETA-CELLS OF NON-INSULIN-DEPENDENT DIABETIC OBESE RATS
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DOI：
10.1152/ajpendo.1994.267.6.e968
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发表时间：
1994-12-01
影响因子：
5.1
通讯作者：
UNGER, RH
中科院分区：
文献类型：
--
作者：
OHNEDA, M;JOHNSON, JH;UNGER, RH
Zucker糖尿病肥胖（ZDF）大鼠发生非胰岛素依赖性糖尿病，同时伴有葡萄糖反应性和GLUT-2（β细胞的高米氏常数葡萄糖转运蛋白）的丧失。为了确定β-细胞葡萄糖代谢的完整性远端的葡萄糖转运和磷酸化的水平，我们检查了离体胰腺的5，10，和20 mM的D-甘油醛和琥珀酸单甲酯，以及葡萄糖的胰岛素反应。糖尿病胰腺对葡萄糖的胰岛素反应比糖尿病发作前的反应低90%，而对甘油醛和琥珀酸的反应分别下降到65%和44%，低于糖尿病前期的反应。糖尿病胰岛的D-[C-14]甘油醛氧化比非糖尿病瘦对照胰岛低74%。我们得出的结论是：1）ZDF大鼠糖尿病中胰岛素对甘油醛和琥珀酸单甲酯以及对葡萄糖的反应受到损害，2）葡萄糖反应的损害大于甘油醛反应的损害，而甘油醛反应的损害又大于琥珀酸单甲酯反应的损害;这种减弱的损伤模式与葡萄糖代谢多个部位的缺陷一致;如果该缺陷完全是由于st代谢后信号传导缺陷，则对葡萄糖及其代谢物的损害应该是相当的。
Zucker diabetic fatty (ZDF) rats develop non-insulin-dependent diabetes mellitus concomitantly with loss of glucose responsiveness and GLUT-2, the high-Michaelis constant glucose transporter of beta-cells. To determine the integrity of beta-cell glucose metabolism distal to the level of glucose transport and phosphorylation, we examined the insulin responses of isolated pancreata to 5, 10, and 20 mM D-glyceraldehyde and monomethylsuccinate, as well as to glucose. The insulin response of diabetic pancreata to glucose was 90% below the response prior to the onset of diabetes, whereas the responses to glyceraldehyde and succinate had declined to 65 and 44%, respectively, below the prediabetic responses. D-[C-14]glyceraldehyde oxidation by diabetic islets was 74% below that of islets from lean nondiabetic controls. We conclude that 1) the insulin responses to glyceraldehyde and monomethylsuccinate, as well as to glucose, are impaired in the diabetes of ZDF rats and 2) the impairment of the glucose response was greater than that of the glyceraldehyde response, which was, in turn, greater than that of the monomethylsuccinate response; this decrescendo pattern of impairment is consistent with defects at multiple sites in glucose metabolism; if the defect were entirely due to st postmetabolic signaling defect, the impairment to glucose and its metabolites should be comparable.