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Maturity Onset Diabetes of the Young 3 (MODY3) is the most common monogenic form of diabetes, characterized by early age of onset (before the age of 25), autosomal dominant transmission and severe defect in insulin secretion [1,2]. MODY accounts for 2-5% of Non-Insulin Dependent Diabetes Mellitus (NIDDM) cases, with MODY3 identified as the most common and severe form, accounting for 65% of all MODY cases and results from loss of function mutations of the transcription factor Hepatocyte Nuclear Factor-1 α (HNF1α). As a result of this, pancreatic islets show reduction in glucose-stimulated insulin secretion response and in beta cell mass, hallmarks of MODY3. Previous work in this laboratory has shown that induction of dominant negative mutant-HNF1a expression results in bioenergetic stress, activation of AMPK and induction of pro-apoptotic BH3-only family protein, Bmf [3].

bmc proceedings

The role of BH3-only protein Bmf in the pathogenesis of dominant negative hepatocyte nuclear factor-1 –induced mature-onset diabetes of the young in transgenic mice