Johnson K H, O'Brien T D, Jordan K, Betsholtz C, Westermark P
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, St. Paul 55108.
Biochem Biophys Res Commun. 1990 Mar 16;167(2):507-13. doi: 10.1016/0006-291x(90)92053-3.
Islet amyloid polypeptide (IAPP) has been implicated by in vitro studies as an inhibitor of insulin-stimulated glucose utilization by skeletal muscle cells and also as an inhibitor of insulin-stimulated insulin secretion by beta cells. Increased expression and production of IAPP by beta cells, as has been suggested to occur in cats with impaired glucose tolerance, could thus contribute substantially to the development of the insulin resistance and impaired insulin release which are the hallmarks of Type 2 diabetes mellitus. The effects of IAPP with respect to glucose metabolism in living animals, however, have not been previously reported. In the present in vivo study we show that synthetic amidated IAPP induced impaired glucose tolerance in each of the 3 cats studied, with dramatic impairment (increases in glucose to T1/2 values of 124% and 234%) in 2 of the 3 cats. Impaired insulin responses were also evident in the 2 cats with the most dramatic states of glucose intolerance. These results provide the most direct evidence to-date that IAPP may have an important role in the development of Type 2 diabetes mellitus.
胰岛淀粉样多肽（IAPP）在体外研究中被认为是骨骼肌细胞胰岛素刺激的葡萄糖利用的抑制剂，也是β细胞胰岛素刺激的胰岛素分泌的抑制剂。β细胞IAPP表达和产生增加，如已被认为在糖耐量受损的猫中发生的那样，因此可能在很大程度上导致胰岛素抵抗的发展和胰岛素释放受损，而这是2型糖尿病的标志。然而，IAPP对活体动物葡萄糖代谢的影响此前尚未见报道。在本体内研究中，我们表明合成的酰胺化IAPP在研究的3只猫中的每一只中都诱导了糖耐量受损，在3只猫中的2只中出现了显著受损（葡萄糖到T1/2值增加了124%和234%）。在2只葡萄糖不耐受最严重的猫中，胰岛素反应受损也很明显。这些结果提供了迄今为止最直接的证据，表明IAPP可能在2型糖尿病的发展中起重要作用。
