title: Incretin effect and glucagon responses to oral and intravenous glucose in patients with maturity-onset diabetes of the young--type 2 and type 3.
abstract: Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgroup of nonautoimmune diabetes, constituting 1-2% of all diabetes. Because little is known about incretin function in patients with MODY, we studied the incretin effect and hormone responses to oral and intravenous glucose loads in patients with glucokinase (GCK)-diabetes (MODY2) and hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), respectively, and in matched healthy control subjects. Both MODY groups exhibited glucose intolerance after oral glucose (most pronounced in patients with HNF1A-diabetes), but only patients with HNF1A-diabetes had impaired incretin effect and inappropriate glucagon responses to OGTT. Both groups of patients with diabetes showed normal suppression of glucagon in response to intravenous glucose. Thus, HNF1A-diabetes, similar to type 2 diabetes, is characterized by an impaired incretin effect and inappropriate glucagon responses, whereas incretin effect and glucagon response to oral glucose remain unaffected in GCK-diabetes, reflecting important pathogenetic differences between the two MODY forms.
authors.affiliation: Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark s.ostoft@dadlnet.dk.
authors.forename: Signe H
authors.initials: SH
authors.lastname: Østoft
authors.affiliation: Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jonatan I
authors.initials: JI
authors.lastname: Bagger
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkFaculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D054795:Incretins; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005941:Glucokinase; D005947:Glucose