Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2003 Nov;22(5):353-62.
doi: 10.1002/humu.10277.

Glucokinase (GCK) Mutations in Hyper- And Hypoglycemia: Maturity-Onset Diabetes of the Young, Permanent Neonatal Diabetes, and Hyperinsulinemia of Infancy

Affiliations
Review

Glucokinase (GCK) Mutations in Hyper- And Hypoglycemia: Maturity-Onset Diabetes of the Young, Permanent Neonatal Diabetes, and Hyperinsulinemia of Infancy

Anna L Gloyn. Hum Mutat. .

Abstract

Glucokinase is a key regulatory enzyme in the pancreatic beta-cell. It plays a crucial role in the regulation of insulin secretion and has been termed the pancreatic beta-cell sensor. Given its central role in the regulation of insulin release, it is understandable that mutations in the gene encoding glucokinase (GCK) can cause both hyperglycemia and hypoglycemia. Heterozygous inactivating mutations in GCK cause maturity-onset diabetes of the young (MODY), characterized by mild hyperglycemia, which is present at birth, but is often only detected later in life during screening for other purposes. Homozygous inactivating GCK mutations result in a more severe phenotype, presenting at birth as permanent neonatal diabetes mellitus (PNDM). Several heterozygous activating GCK mutations that cause hypoglycemia have also been reported. A total of 195 mutations in the GCK gene have been described, in a total of 285 families. There are no common mutations and the mutations are distributed throughout the gene. Mutations that cause hypoglycemia are located in various exons in a discrete region of the protein termed the heterotropic allosteric activator site. The identification of a GCK mutation in hyper- and hypoglycemia has implications for the clinical course and clinical management of the disorder.

Similar articles

See all similar articles

Cited by 68 articles

See all "Cited by" articles

Publication types

LinkOut - more resources

Feedback