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. 1997 Feb 15;322(Pt 1):57–63. doi: 10.1042/bj3220057

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

P Kesavan 1, L Wang 1, E Davis 1, A Cuesta 1, I Sweet 1, K Niswender 1, M A Magnuson 1, F M Matschinsky 1
PMCID: PMC1218158  PMID: 9078243

Abstract

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.

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Selected References

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