AMYLIN FOUND IN AMYLOID DEPOSITS IN HUMAN TYPE-2 DIABETES-MELLITUS MAY BE A HORMONE THAT REGULATES GLYCOGEN-METABOLISM IN SKELETAL-MUSCLE
AMYLIN FOUND IN AMYLOID DEPOSITS IN HUMAN TYPE-2 DIABETES-MELLITUS MAY BE A HORMONE THAT REGULATES GLYCOGEN-METABOLISM IN SKELETAL-MUSCLE
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DOI：
10.1073/pnas.85.20.7763
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发表时间：
1988-10-01
影响因子：
11.1
通讯作者：
REID, KBM
中科院分区：
文献类型：
--
作者：
COOPER, GJS;LEIGHTON, B;REID, KBM
最近从2型（非胰岛素依赖型）糖尿病患者的胰岛淀粉样蛋白中分离并鉴定了糖尿病相关肽，并且在正常和2型糖尿病受试者的胰岛B细胞中证实了与该肽的抗体的免疫反应性。鉴于本文中提出的证据表明，这种37个氨基酸的肽可能是存在于正常个体中的激素，我们现在建议将“糖尿病相关肽”命名为“胰淀素”。由于胰岛内淀粉样沉积的胰淀素增加是2型糖尿病的特征，因此进行以下研究以检查胰淀素对外周葡萄糖代谢的可能影响。全胰淀素合成通过使用固相技术，通过在稀水溶液中氧化形成二硫键，并通过冻干回收肽。本实验采用离体大鼠比目鱼肌和脂肪细胞两种标本，研究胰淀素对糖代谢的影响。在骨骼肌暴露于120 nM胰淀素1小时，有一个显着的基础和次最大的胰岛素刺激的糖原合成率下降，这导致胰岛素刺激的葡萄糖摄取率显着降低。在用胰淀素处理的肌肉中，在刺激未处理（对照）肌肉中葡萄糖摄取的一半所需的胰岛素浓度下没有反应。与此形成鲜明对比的是，胰淀素对基础或胰岛素刺激的葡萄糖掺入分离的脂肪细胞中的CO2或三酰甘油的速率没有影响。因此，胰淀素可能是2型糖尿病中胰岛素抵抗的病因学因素，因为胰岛淀粉样蛋白中肽的沉积以及骨骼肌中葡萄糖摄取和糖原合成速率的降低都是这种病症的特征。
Diabetes-associated peptide has recently been isolated and characterized from the amyloid of the islets of Langerhans in type 2 (non-insulin-dependent) diabetics, and immunoreactivity with antibodies to the peptide has been demonstrated in islet B cells of both normal and type 2 diabetic subjects. In view of the evidence presented in this paper that this 37-amino acid peptide may be a hormone present in normal individuals, we now propose the name "amylin" to replace "diabetes-associated peptide". Because increase amylin, deposited as amyloid within the islets of Langerhans, is characteristic of type 2 diabetes, the study below was performed to examine the possible effects of amylin on peripheral glucose metabolism. Whole amylin was synthesized by using solid-phase techniques, with formation of the disulfide linkage by oxidation in dilute aqueous solution and recovery of the peptide by lyophilization. The effect of amylin on glucose metabolism were studied in two preparations in vitro, isolated rat soleus muscle strips and isolated rat adipocytes. In skeletal muscle exposed to 120 nM amylin for 1 hr, there was a marked decrease in both basal and submaximally insulin-stimulated rates of glycogen synthesis, which resulted in significant reduction in the rates of insulin-stimulated glucose uptake. In muscles treated with amylin there was no response at the concentration of insulin required to stimulate glucose uptake half-maximally in untreated (control) muscles. In marked contrast, amylin had no effect on either basal or insulin-stimulated rates of glucose incorporation into either CO2 or triacylglycerol in isolated adipocytes. Therefore, amylin may be a factor in the etiology of the insulin resistance in type 2 diabetes mellitus, as both deposition of the peptide in islet amyloid and decreased rates of glucose uptake and glycogen synthesis in skeletal muscle are characteristic of this conditions.