Molecular and physiological basis for maturity onset diabetes of youth

Publisher Website
Google Scholar
Abstract
Although maturity onset diabetes of the young (MODY) was first described in the 1960s as a paradigm for the heterogeneity of diabetes, not until recent years has the extent of this heterogeneity become apparent through the identification of the underlying molecular causes. Mutations in the hepatocyte nuclear factor (HNF) genes seem to cause impaired beta cell function by interfering with ATP generation by glycolysis in the beta cells. The HNF-1α and HNF-4α genes are regulated in a network of transcription factors including HNF-3α and HNF-3β. Mutations in the glucokinase gene cause MODY2 as well as a rare form of familial hyperinsulinism and low birth weight in offspring if the offspring carries the mutation. MODY is clearly more heterogeneous than thought thus far, and despite the identification of mutations in the IPF-1 and HNF-1β genes as causes of MODY4 and MODY5, there are still unexplained forms of MODY. It is still an open question whether subtle regulatory mutations in MODY genes contribute to late-onset type 2 diabetes. Whether these transcription factors can be used as therapeutic targets in the future needs to be shown.