title: Altered insulin secretory responses to glucose in subjects with a mutation in the MODY1 gene on chromosome 20.
abstract: This study was undertaken to test the hypothesis that the diabetes susceptibility gene on chromosome 20q12 responsible for maturity-onset diabetes of the young (MODY) in a large kindred, the RW family, results in characteristic alterations in the dose-response relationships between plasma glucose concentration and insulin secretion rate (ISR) that differentiate this form of MODY from MODY in subjects with glucokinase mutations. Ten marker-positive subjects and six matched nondiabetic marker-negative subjects from the RW family received graded intravenous glucose infusions on two occasions separated by a 42-h continuous intravenous glucose infusion designed to prime the beta-cell to secrete more insulin in response to glucose. ISR was derived by deconvolution of peripheral C-peptide levels. Basal glucose and insulin levels were similar in marker-negative and marker-positive groups (5.3 +/- 0.2 vs. 5.0 +/- 0.2 mmol/l, P > 0.2, and 86.1 +/- 3.9 vs. 63.7 +/- 12.1 pmol/l, P > 0.1, respectively). However, the marker-positive subjects had defective insulin secretory responses to an increase in plasma glucose concentrations. Thus, as the glucose concentration was raised above 7 mmol/l, the slope of the curve relating glucose and ISR was significantly blunted in the marker-positive subjects (13 +/- 4 vs. 68 +/- 8 pmol.min-1.mmol-1 x 1, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Chicago, IL 60637, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Byrne
authors.forename: J
authors.initials: J
authors.lastname: Sturis
authors.forename: S S
authors.initials: SS
authors.lastname: Fajans
authors.forename: F J
authors.initials: FJ
authors.lastname: Ortiz
authors.forename: A
authors.initials: A
authors.lastname: Stoltz
authors.forename: M
authors.initials: M
authors.lastname: Stoffel
authors.forename: M J
authors.initials: MJ
authors.lastname: Smith
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
authors.forename: J B
authors.initials: JB
authors.lastname: Halter
authors.forename: K S
authors.initials: KS
authors.lastname: Polonsky
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005190:Family; D005260:Female; D005796:Genes / Q000235:genetics; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009154:Mutation
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose