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.
| Original language | English |
|---|---|
| Journal | Diabetologia |
| Volume | 40 |
| Issue number | 8 |
| Pages (from-to) | 940-6 |
| Number of pages | 7 |
| ISSN | 0012-186X |
| Publication status | Published - Aug 1997 |
Keywords
- Alleles
- Animals
- Autoradiography
- Base Sequence
- Biopsy
- Blotting, Southern
- Calcium-Calmodulin-Dependent Protein Kinases
- Chromosome Mapping
- Cricetinae
- DNA Mutational Analysis
- DNA Primers
- Diabetes Mellitus, Type 2
- Glycogen Synthase Kinases
- Humans
- In Situ Hybridization, Fluorescence
- Muscle, Skeletal
- Mutation
- Polymerase Chain Reaction
- Polymorphism, Single-Stranded Conformational
