Structural instability of mutant beta-cell glucokinase: implications for the molecular pathogenesis of maturity-onset diabetes of the young (type-2).

Kesavan P, Wang L, Davis E, Cuesta A, Sweet I, Niswender K, Magnuson MA, Matschinsky FM
Biochem J. 1997 322 ( Pt 1): 57-63

PMID: 9078243 · PMCID: PMC1218158 · DOI:10.1042/bj3220057

The catalytic function and thermal stability of wild-type and mutant recombinant human pancreatic beta-cell glucokinase was investigated. The mutants E70K and E300K, which are thought to be the cause of impaired insulin production by the pancreatic beta-cell and decreased glucose uptake by the liver of patients with maturity-onset diabetes of the young, were found to be functionally indistinguishable from the wild-type, i.e. their kcat.S0.5, inflection point and h were normal. However, these two mutants showed markedly reduced stability under a variety of test conditions. Glucokinase instability, not low enzyme catalytic activity, may be the cause of diabetes mellitus with E70K and E300K mutants.

MeSH Terms (8)

Diabetes Mellitus, Type 2 Enzyme Stability Glucokinase Humans Islets of Langerhans Kinetics Mutation Recombinant Proteins

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