Abnormal regulation of hepatic glucose output in maturity-onset diabetes of the young caused by a specific mutation of the glucokinase gene

Détails

ID Serval
serval:BIB_7468FC3BFC05
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Abnormal regulation of hepatic glucose output in maturity-onset diabetes of the young caused by a specific mutation of the glucokinase gene
Périodique
Diabetes
Auteur(s)
Tappy  L., Dussoix  P., Iynedjian  P., Henry  S., Schneiter  P., Zahnd  G., Jequier  E., Philippe  J.
ISSN
0012-1797 (Print)
Statut éditorial
Publié
Date de publication
02/1997
Volume
46
Numéro
2
Pages
204-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
Résumé
A subtype of maturity-onset diabetes of the young (MODY) is caused by mutations of the glucokinase gene, an enzyme expressed in pancreatic beta-cells and the liver. To assess the consequences of a functional alteration of glucokinase at the level of the liver, endogenous (hepatic) glucose production and glucose cycling (an indirect assessment of hepatic glucokinase activity) were measured with 2-2H glucose and 6,6-2H glucose in patients who developed MODY because of the V203A mutation of glucokinase, and in control subjects at similar levels of glycemia. Measurements were performed in the postabsorptive state and after ingestion of 13C-labeled glucose. In the postabsorptive state, MODY patients had normal glucose production (10.9 +/- 1.3 vs. 11.3 +/- 0.6 micromol x kg(-1) x min(-1)) but decreased glucose cycling (0.6 +/- 0.3 vs. 1.5 +/- 0.3 micromol x kg(-1) x min(-1); P < 0.05) when compared with control subjects. However, at plasma glucose and insulin levels similar to those observed in MODY patients, control subjects' glucose production was markedly lower (3.2 +/- 1.5 micromol x kg(-1) x min(-1). After glucose ingestion, endogenous glucose production was reduced by only 29% in MODY patients compared with 80% in control subjects at a similar level of hyperglycemia (P < 0.05). This suggests that the V203A mutation of glucokinase results in decreased activity of glucokinase in liver cells. Thus endogenous glucose production is inadequately inhibited by hyperglycemia in MODY patients, possibly as a result of impaired hepatic glucokinase activity. These alterations contribute to the pathogenesis of hyperglycemia.
Mots-clé
Adult Blood Glucose/metabolism C-Peptide/blood Calorimetry Diabetes Mellitus, Type 2/enzymology/*genetics Female Glucokinase/*genetics Glucose/metabolism Humans Insulin/blood Liver/metabolism Male Middle Aged Mutation Oxidation-Reduction
Pubmed
Web of science
Création de la notice
24/01/2008 14:36
Dernière modification de la notice
03/03/2018 18:21
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