Activating Mutations in Kir6.2 and Neonatal Diabetes
Top Cited Papers
- 1 September 2005
- journal article
- review article
- Published by American Diabetes Association in Diabetes
- Vol. 54 (9) , 2503-2513
- https://doi.org/10.2337/diabetes.54.9.2503
Abstract
Closure of ATP-sensitive K+ channels (KATP channels) in response to metabolically generated ATP or binding of sulfonylurea drugs stimulates insulin release from pancreatic β-cells. Heterozygous gain-of-function mutations in the KCJN11 gene encoding the Kir6.2 subunit of this channel are found in ∼47% of patients diagnosed with permanent diabetes at transient neonatal diabetes > permanent neonatal diabetes > DEND syndrome channels. Sulfonylureas still close mutated KATP channels, and many patients can discontinue insulin injections and show improved glycemic control when treated with high-dose sulfonylurea tablets. In conclusion, the finding that Kir6.2 mutations can cause neonatal diabetes has enabled a new therapeutic approach and shed new light on the structure and function of the Kir6.2 subunit of the KATP channel.Keywords
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