期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：26
页码：16992-16997
DOI：10.1073/pnas.012479199
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：ATP-sensitive K+ (KATP) channels couple cell metabolism to electrical activity. To probe the role of KATP in glucose-induced insulin secretion, we have generated transgenic mice expressing a dominant-negative, GFP-tagged KATP channel subunit in which residues 132-134 (Gly-Tyr-Gly) in the selectivity filter were replaced by Ala-Ala-Ala, under control of the insulin promoter. Transgene expression was confirmed by both beta cell-specific green fluorescence and complete suppression of channel activity in those cells ({approx}70%) that did fluoresce. Transgenic mice developed normally with no increased mortality and displayed normal body weight, blood glucose levels, and islet architecture. However, hyperinsulinism was evident in adult mice as (i) a disproportionately high level of circulating serum insulin for a given glucose concentration ({approx}2-fold increase in blood insulin), (ii) enhanced glucose-induced insulin release from isolated islets, and (iii) mild yet significant enhancement in glucose tolerance. Enhanced glucose-induced insulin secretion results from both increased glucose sensitivity and increased release at saturating glucose concentration. The results suggest that incomplete suppression of KATP channel activity can give rise to a maintained hyperinsulinism.
