TY - JOUR

T1 - Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3alpha and beta isoforms in patients with NIDDM

AU - Hansen, L

AU - Arden, K C

AU - Rasmussen, S B

AU - Viars, C S

AU - Vestergaard, H

AU - Hansen, T

AU - Møller, A M

AU - Woodgett, J R

AU - Pedersen, O

PY - 1997/8

Y1 - 1997/8

N2 - 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.

AB - 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.

KW - Alleles

KW - Animals

KW - Autoradiography

KW - Base Sequence

KW - Biopsy

KW - Blotting, Southern

KW - Calcium-Calmodulin-Dependent Protein Kinases

KW - Chromosome Mapping

KW - Cricetinae

KW - DNA Mutational Analysis

KW - DNA Primers

KW - Diabetes Mellitus, Type 2

KW - Glycogen Synthase Kinases

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Muscle, Skeletal

KW - Mutation

KW - Polymerase Chain Reaction

KW - Polymorphism, Single-Stranded Conformational

M3 - Journal article

C2 - 9267989

VL - 40

SP - 940

EP - 946

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 8

ER -