Gebre-Medhin S, Mulder H, Pekny M, Westermark G, Törnell J, Westermark P, Sundler F, Ahrén B, Betsholtz C
Department of Medical Biochemistry, Göteborg University, Sweden.
Biochem Biophys Res Commun. 1998 Sep 18;250(2):271-7. doi: 10.1006/bbrc.1998.9308.
Islet amyloid polypeptide (IAPP or amylin) is costored and cosecreted with insulin and may regulate insulin secretion and blood glucose handling. However, the role and importance of endogenous IAPP in the regulation of insulin release and glucose homeostasis have been controversial. Here we report on the generation and phenotypic analysis of IAPP-deficient mice. These mice have normal, or near to normal, basal levels of circulating insulin and glucose. However, following glucose administration, IAPP-deficient males presented increased insulin responses paralleled with a more rapid blood glucose elimination compared to wild-type controls. Blood glucose elimination was also found to be enhanced in IAPP-deficient females, but the insulin response in this gender did not differ from controls. In a transgenic rescue experiment, using an insulin-promoter human-IAPP fusion gene, insulin responses and blood glucose elimination were reversed in IAPP-deficient males, whereas the female phenotype appeared unaffected. Our results provide the first firm evidence of a physiological role for endogenous IAPP and indicate that IAPP, apparently in a gender-dependent manner, limits the degree of glucose-induced insulin secretion and the rate of blood glucose elimination.
胰岛淀粉样多肽（IAPP或胰淀素）与胰岛素共同储存和分泌，可能调节胰岛素分泌和血糖处理。然而，内源性IAPP在调节胰岛素释放和葡萄糖稳态中的作用和重要性一直存在争议。在此，我们报告IAPP缺陷小鼠的产生和表型分析。这些小鼠的循环胰岛素和葡萄糖基础水平正常或接近正常。然而，给予葡萄糖后，与野生型对照相比，IAPP缺陷雄性小鼠的胰岛素反应增强，同时血糖消除更快。还发现IAPP缺陷雌性小鼠的血糖消除也增强，但该性别小鼠的胰岛素反应与对照无差异。在一项转基因拯救实验中，使用胰岛素启动子人IAPP融合基因，IAPP缺陷雄性小鼠的胰岛素反应和血糖消除得到逆转，而雌性表型似乎未受影响。我们的结果为内源性IAPP的生理作用提供了首个确凿证据，并表明IAPP显然以性别依赖的方式限制了葡萄糖诱导的胰岛素分泌程度和血糖消除速率。
