Glucose utilization and production in patients with maturity-onset diabetes of the young caused by a mutation of the hepatocyte nuclear factor-1alpha gene

Details

Serval ID
serval:BIB_41B43BC27041
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Glucose utilization and production in patients with maturity-onset diabetes of the young caused by a mutation of the hepatocyte nuclear factor-1alpha gene
Journal
Diabetes
Author(s)
Surmely  J. F., Guenat  E., Philippe  J., Dussoix  P., Schneiter  P., Temler  E., Vaxillaire  M., Froguel  P., Jequier  E., Tappy  L.
ISSN
0012-1797 (Print)
Publication state
Published
Issued date
09/1998
Volume
47
Number
9
Pages
1459-63
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Abstract
Mutations of the hepatocyte nuclear factor (HNF)-1alpha gene cause impaired insulin secretion and hyperglycemia in patients with maturity-onset diabetes of the young (MODY)3. Whether these mutations also affect glucose metabolism in tissues other than the beta-cell has not yet been documented. We therefore assessed, in five MODY3 patients and a dozen healthy control subjects, insulin secretion, oxidative and nonoxidative glucose disposal, and glucose production during a two-step hyperglycemic clamp and a euglycemic hyperinsulinemic (0.4 mU x kg(-1) x min(-1)) clamp. Compared with healthy control subjects, MODY3 patients had higher fasting plasma glucose (+100%) but similar rates of fasting glucose production and oxidation. Both the early and late phases of insulin secretion were virtually abolished during the hyperglycemic clamp, and glucose production was suppressed by only 43% in MODY3 patients vs. 100% in healthy control subjects. The rate of glucose infusion required to produce a 5 mmol/l increase above basal glycemia was reduced by 30%, net nonoxidative glucose disposal (which is equal to net glycogen deposition) was inhibited by 39%, and net carbohydrate oxidation during hyperglycemia was 25% lower in MODY3 patients compared with control subjects. Insulin-stimulated glucose utilization and oxidation measured during the hyperinsulinemic clamp (at approximately 200 pmol/l insulin) were identical in MODY3 patients and in healthy control subjects, indicating that peripheral insulin sensitivity was not altered. Suppression of endogenous glucose production was, however, mildly impaired. It is concluded that MODY3 patients have severely depressed glucose-induced insulin secretion. The development of hyperglycemia in these patients appears to be caused by a decreased stimulation of glucose utilization, oxidation, and nonoxidative glucose disposal as well as by a blunted suppression of endogenous glucose output. These phenomena are essentially secondary to insulinopenia, whereas insulin sensitivity remains intact.
Keywords
Adult Blood Glucose/drug effects/*metabolism DNA-Binding Proteins/genetics Diabetes Mellitus, Type 2/*genetics/*metabolism Fatty Acids, Nonesterified/blood Female Glucagon/blood Glucose/biosynthesis/*metabolism Glucose Clamp Technique Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 1-beta Humans Infusions, Intravenous Insulin/administration & dosage/blood/pharmacology Kinetics Male Middle Aged *Mutation *Nuclear Proteins Reference Values Time Factors Transcription Factors/*genetics
Pubmed
Web of science
Create date
24/01/2008 14:36
Last modification date
20/08/2019 14:42
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