title: Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3alpha and beta isoforms in patients with NIDDM.
abstract: Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active dephosphorylated state. In a search for genetic defects responsible for the decreased insulin stimulated glycogen synthesis seen in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their glucose-tolerant first-degree relatives we have performed mutational analysis of the coding region of the 2 isoforms of GSK-3alpha and GSK-3beta in 72 NIDDM patients and 12 control subjects. No structural changes were detected apart from a few silent mutations. Mapping of the GSK-3alpha to chromosome 19q13.1-13.2 and the GSK-3beta to chromosome 3q13.3-q21 outside known genetic loci linked to NIDDM further makes it unlikely that these genes are involved in the pathogenesis of common forms of NIDDM.
authors.affiliation: Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Hansen
authors.forename: K C
authors.initials: KC
authors.lastname: Arden
authors.forename: S B
authors.initials: SB
authors.lastname: Rasmussen
authors.forename: C S
authors.initials: CS
authors.lastname: Viars
authors.forename: H
authors.initials: H
authors.lastname: Vestergaard
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: A M
authors.initials: AM
authors.lastname: Møller
authors.forename: J R
authors.initials: JR
authors.lastname: Woodgett
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D000483:Alleles; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001706:Biopsy; D015139:Blotting, Southern; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000145:classification / Q000235:genetics*; D002874:Chromosome Mapping; D006224:Cricetinae; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D038341:Glycogen Synthase Kinases; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D017931:DNA Primers; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases