Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3α and β isoforms in patients with NIDDM

Autor: Hansen, L., Arden, K. C., Rasmussen, S. B., Viars, C. S., Vestergaard, H., Hansen, T., Møller, A. M., Woodgett, J. R., Pedersen, O.
Zdroj: Diabetologia; July 1997, Vol. 40 Issue: 8 p940-946, 7p
Abstrakt: 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-3α and GSK-3βin 72 NIDDM patients and 12 control subjects. No structural changes were detected apart from a few silent mutations. Mapping of the GSK-3α to chromosome 19q13.1–13.2 and the GSK-3βto 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. [Diabetologia (1997) 40: 940–946]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-3α and GSK-3βin 72 NIDDM patients and 12 control subjects. No structural changes were detected apart from a few silent mutations. Mapping of the GSK-3α to chromosome 19q13.1–13.2 and the GSK-3βto 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. [Diabetologia (1997) 40: 940–946]
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