Sowa R, Sanke T, Hirayama J, Tabata H, Furuta H, Nishimura S, Nanjo K
First Department of Medicine, Wakayama University of Medical Science, Japan.
Diabetologia. 1990 Feb;33(2):118-20. doi: 10.1007/BF00401051.
Islet amyloid polypeptide is a 37 amino acid hormone-like peptide which is the major protein component of islet amyloid deposits commonly found in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Recent studies indicate that a physiologically active form of this peptide appears to be carboxyamidated and secreted from the insulin-producing beta cell. In order to clarify the possible in vivo actions of islet amyloid polypeptide, we have studied the effects of synthesized islet amyloid polypeptide-amide on peripheral glucose utilization by performing hyperinsulinaemic euglycaemic glucose clamp studies on dogs. Exogenously administered islet amyloid polypeptide-amide (an infusion from 1.0 to 100 micrograms.kg-1.h-1, over 2 h) inhibited the insulin-stimulated glucose disposal rate in a dose dependent manner. Twenty-five micrograms.kg-1.h-1 of islet amyloid polypeptide-amide infused via a peripheral vein significantly lowered the glucose disposal rate by 20% (from 17.4 +/- 1.7 to 14.4 +/- 1.7 mg.kg-1.min-1, n = 5, p less than 0.01). These findings suggest that islet amyloid polypeptide-amide causes peripheral insulin resistance in vivo.
胰岛淀粉样多肽是一种由37个氨基酸组成的类激素肽，是2型（非胰岛素依赖型）糖尿病患者胰岛淀粉样沉积物中的主要蛋白质成分。最近的研究表明，这种肽的生理活性形式似乎是羧基酰胺化的，并由产生胰岛素的β细胞分泌。为了阐明胰岛淀粉样多肽可能的体内作用，我们通过对狗进行高胰岛素正常血糖葡萄糖钳夹研究，研究了合成的胰岛淀粉样多肽酰胺对周围葡萄糖利用的影响。外源性给予胰岛淀粉样多肽酰胺（在2小时内以1.0至100微克·千克⁻¹·小时⁻¹的速度输注）以剂量依赖的方式抑制胰岛素刺激的葡萄糖处置率。通过外周静脉输注25微克·千克⁻¹·小时⁻¹的胰岛淀粉样多肽酰胺可使葡萄糖处置率显著降低20%（从17.4±1.7降至14.4±1.7毫克·千克⁻¹·分钟⁻¹，n = 5，p<0.01）。这些发现表明，胰岛淀粉样多肽酰胺在体内会导致外周胰岛素抵抗。
