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From congenital hyperinsulinism to diabetes mellitus: the role of pancreatic β‐cell K ATP channels
Author(s) -
Hussain Khalid,
Cosgrove Karen E
Publication year - 2005
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/j.1399-543x.2005.00109.x
Subject(s) - medicine , hyperinsulinism , beta cell , diabetes mellitus , congenital hyperinsulinism , endocrinology , insulin resistance , islet
Pancreatic β‐cell adenosine triphosphate (ATP)‐sensitive potassium (K ATP ) channels play a pivotal role in linking glucose metabolism to regulated insulin secretion. K ATP channels are hetero‐ octameric complexes comprising two subunits Kir6.2 and sulfonylurea receptor 1 (SUR1). Changes in the intracellular concentration of nucleotides (ATP) cause alterations in the resting and opening state of the K ATP channels. Loss‐of‐function mutations in the genes encoding the two subunits of K ATP channels lead to the most common form of congenital hyperinsulinism (CHI). This causes persistent and severe hypoglycemia in the neonatal and infancy period. CHI can cause mental retardation and epilepsy if not treated properly. On the other hand, now there is evidence of an association between polymorphisms in the Kir6.2 gene and type 2 diabetes mellitus, mutations in the Kir6.2 gene and neonatal diabetes mellitus, and mutations in the SUR1 gene and diabetes mellitus. Interestingly, for reasons that are unclear at present, mice knockout models of K ATP channels are different from the human phenotype of CHI. This article is a review focusing on how abnormalities in the pancreatic β‐cell K ATP channels can lead to severe hypoglycemia on the one hand and diabetes mellitus on the other.