首页> 外文期刊>American Journal of Physiology >Impaired phasic insulin and amylin secretion in diabetic rats.
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Impaired phasic insulin and amylin secretion in diabetic rats.

机译:糖尿病大鼠的阶段性胰岛素和胰岛淀粉样多肽分泌受损。

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We have proposed that a hyperstimulated insulin secretion causing beta-cell degranulation is the basis for the impaired glucose-potentiated insulin secretion in type 2 diabetes ("overworked beta-cell"). To confirm this idea, we previously investigated tolbutamide-infused euglycemic rats. Two novel kinds of beta-cell dysfunction were observed: altered phasic glucose-potentiated insulin secretion with preferential sparing of the first phase and a raised secreted ratio of amylin to insulin. The current study tested these parameters in 90% (intact beta-cell insulin stores) and 95% (markedly lowered insulin stores) pancreatectomized (Px) diabetic rats. Rats underwent pancreas perfusion 5-6 wk postsurgery. Controls showed nonchanging insulin secretion during a 20-min perfusion of 16.7 mM glucose + 10 mM arginine. In contrast, both Px groups showed an altered phasic pattern, with the first phase being supernormal (for the beta-cell mass) but the second phase reduced in tandem with the insulin content. Amylin secretion from control and 90% Px rats paralleled the insulin output, so that the amylin-to-insulin ratio averaged 0. 12 +/- 0.03% in the controls and 0.16 +/- 0.01% in the 90% Px rats over the two secretory phases. In contrast, the amylin-to-insulin ratio in 95% Px rats equaled that of controls during the first phase (0.12 +/- 0.1%) but was twice normal during the second phase (0.32 +/- 0.4%). These results confirm the validity of the overworked beta-cell schema by showing identical beta-cell functional defects in Px rats and tolbutamide-infused normoglycemic rats.
机译:我们已经提出,引起β细胞脱粒的过度刺激的胰岛素分泌是2型糖尿病(“过度劳累的β细胞”)中葡萄糖增强的胰岛素分泌受损的基础。为了证实这一想法,我们先前研究了注射甲苯磺丁酰胺的正常血糖大鼠。观察到两种新型的β细胞功能异常:第一阶段优先保留的阶段性葡萄糖增强型胰岛素分泌发生改变,以及胰岛淀粉样多肽与胰岛素的分泌比例升高。当前的研究在90%(完整的β细胞胰岛素存储库)和95%(显着降低的胰岛素存储库)的全胰腺切除(Px)糖尿病大鼠中测试了这些参数。大鼠在术后5-6周接受胰脏灌注。对照组显示在16.7 mM葡萄糖+ 10 mM精氨酸的20分钟灌注过程中胰岛素的分泌不变。相反,两个Px组均显示出改变的相位模式,第一阶段为超正常状态(针对β细胞质量),但第二阶段与胰岛素含量串联下降。对照和90%Px大鼠分泌的胰岛淀粉样多肽分泌与胰岛素输出量平行,因此对照组中90%Px大鼠中胰岛淀粉样多肽与胰岛素的比率平均为0. 12 +/- 0.03%,而90%Px大鼠中胰岛淀粉-胰岛素比率平均为0.16 +/- 0.01%。两个分泌阶段。相反,在95%Px大鼠中,胰岛淀粉样多肽与胰岛素的比率在第一阶段等于对照组(0.12 +/- 0.1%),但在第二阶段是正常的两倍(0.32 +/- 0.4%)。这些结果通过显示Px大鼠和注入甲苯磺丁酰胺的正常血糖大鼠中相同的β细胞功能缺陷,证实了过度劳累的β细胞模式的有效性。

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