EFFECT OF CHRONIC HYPERGLYCEMIA ON INVIVO INSULIN-SECRETION IN PARTIALLY PANCREATECTOMIZED RATS

EFFECT OF CHRONIC HYPERGLYCEMIA ON INVIVO INSULIN-SECRETION IN PARTIALLY PANCREATECTOMIZED RATS
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DOI:
10.1172/jci113157
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发表时间:
1987-10-01
影响因子:
15.9
通讯作者:
DEFRONZO, RA
DEFRONZO, RA
中科院分区:
医学1区
文献类型:
--
作者:
ROSSETTI, L;SHULMAN, GI;DEFRONZO, RA

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在清醒的非应激大鼠模型中,我们研究了慢性(4wk)高血糖对体内胰岛素分泌的影响。为了使血糖水平正常化,对三组动物进行了检查:对照组、胰腺部分切除(90%)和胰腺部分切除加根茎叶苷。评估精氨酸(2 MM)、高血糖(+100 mg/dl)和精氨酸加高血糖对胰岛素分泌的影响。糖尿病动物与对照组动物相比,观察到三种特殊的变化:(A)第一和第二阶段对高血糖的胰岛素反应不足;(B)在基础血糖条件下对精氨酸增强作用的胰岛素反应增强;(C)高血糖不能增强高于基础血糖条件下观察到的精氨酸的增强作用。在糖尿病大鼠中,通过根茎叶皂苷治疗使血糖曲线正常化,完全纠正了所有三种β细胞异常。这些结果表明,慢性高血糖可导致体内胰岛素分泌缺陷,当正常血糖恢复时,这种缺陷是可逆的。
We have examined the effect of chronic (4 wk) hyperglycemia on insulin secretion in vivo in an awake, unstressed rat model. Three groups of animals were examined: control, partial (90%) pancreatectomy, and partial pancreatectomy plus phlorizin, in order to normalize plasma glucose levels. Insulin secretion in response to arginine (2 mM), hyperglycemia (+100 mg/dl), and arginine plus hyperglycemia was evaluated. In diabetic compared with control animals three specific alterations were observed: (a) a deficient insulin response, in both first and second phases, to hyperglycemia; (b) an augmented insulin response to the potentiating effect of arginine under basal glycemic conditions; and (c) an inability of hyperglycemia to augment the potentiating effect of arginine above that observed under basal glycemic conditions. Normalization of the plasma glucose profile by phlorizin treatment in diabetic rats completely corrected all three beta cell abnormalities. These results indicate that chronic hyperglycemia can lead to a defect in in vivo insulin secretion which is reversible when normoglycemia is restored.