Mouse models of ¦Â-cell K_ATP channel dysfunction

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• 作者：Melissa F. Brereton ; Frances M. Ashcroft
• 刊名：Drug Discovery Today: Disease Models
• 出版年：2013
• 出版时间：Summer, 2013
• 年：2013
• 卷：10
• 期：2
• 页码：e101-e109
• 全文大小：291 K

文摘

ATP-sensitive K⁺ (K_ATP) channels in pancreatic ¦Â-cells couple glucose metabolism to insulin secretion. Reduced K_ATP channel activity produces excessive insulin release and hyperinsulinism whereas increased K_ATP channel activity leads to lower insulin secretion and diabetes. Paradoxically, mice with genetic deletion of K_ATP channels, or loss-of-function mutations, are only transiently hypoglycaemic during the neonatal period and often display reduced glucose-stimulated insulin secretion subsequently. Mice with K_ATP channel gain-of-function mutations are hyperglycaemic and have impaired glucose-stimulated insulin secretion, a phenotype that accurately mimics human diabetes. This review discusses how mice expressing altered K_ATP channels have provided valuable insight into ¦Â-cell function.