{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T06:12:26Z","timestamp":1793340746926,"version":"4.5.0"},"reference-count":96,"publisher":"American Diabetes Association","issue":"11","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,11,1]]},"abstract":"<jats:p>The ATP-sensitive K+ channel (KATP channel) senses metabolic changes in the pancreatic \u03b2-cell, thereby coupling metabolism to electrical activity and ultimately to insulin secretion. When KATP channels open, \u03b2-cells hyperpolarize and insulin secretion is suppressed. The prediction that KATP channel \u201coveractivity\u201d should cause a diabetic state due to undersecretion of insulin has been dramatically borne out by recent genetic studies implicating \u201cactivating\u201d mutations in the Kir6.2 subunit of KATP channel as causal in human diabetes. This article summarizes the emerging picture of KATP channel as a major cause of neonatal diabetes and of a polymorphism in KATP channel (E23K) as a type 2 diabetes risk factor. The degree of KATP channel \u201coveractivity\u201d correlates with the severity of the diabetic phenotype. At one end of the spectrum, polymorphisms that result in a modest increase in KATP channel activity represent a risk factor for development of late-onset diabetes. At the other end, severe \u201cactivating\u201d mutations underlie syndromic neonatal diabetes, with multiple organ involvement and complete failure of glucose-dependent insulin secretion, reflecting KATP channel \u201coveractivity\u201d in both pancreatic and extrapancreatic tissues.<\/jats:p>","DOI":"10.2337\/diabetes.54.11.3065","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"3065-3072","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":152,"title":["Diabetes and Insulin Secretion"],"prefix":"10.2337","volume":"54","author":[{"given":"Joseph C.","family":"Koster","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Alan","family":"Permutt","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin G.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031217125576800_R1","doi-asserted-by":"crossref","unstructured":"Ashcroft FM, Rorsman P: ATP-sensitive K+ channels: a link between B-cell metabolism and insulin secretion. Biochem Soc Trans\u200818:109\u2013111,1990","DOI":"10.1042\/bst0180109"},{"key":"2022031217125576800_R2","doi-asserted-by":"crossref","unstructured":"Aguilar-Bryan L, Bryan J: Molecular biology of adenosine triphosphate-sensitive potassium channels. 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