Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3alpha and beta isoforms in patients with NIDDM.
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.
Hansen
L
L
Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark.
Arden
K C
KC
Rasmussen
S B
SB
Viars
C S
CS
Vestergaard
H
H
Hansen
T
T
Møller
A M
AM
Woodgett
J R
JR
Pedersen
O
O
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
D017931:DNA Primers; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases