Medical Biochemistry

It has been estimated that 246 million people worldwide have diabetes. In Japan, nationwide study indicates that one out of three people aged 40 or more have diabetes (including the patients with possibility of diabetes). Impaired insulin secretion by pancreatic β-cells and insulin resistance in liver are essential pathophysiology of type 2 diabetes. Thus, it is necessary to clarify the molecular mechanism of the insulin secretion defect and insulin resistance. We found that genetic mutations in the genes encoding hepatocyte nuclear factors (HNFs) cause subtypes of type 2 diabetes (maturity-onset diabetes of the young: MODY) (Nature 1996a, 1996b, Nature Genet. 1997, 2008, PNAS 2002, Cell Metabolism 2005, JBC 2017). We are attempting to clarify the molecular mechanisms of impaired insulin secretion in type 2 diabetes by focusing these transcription factors. In addition, we recently found that sirtuins, NAD dependent deacetylase which is related life span, are involved in the regulation of metabolism (Cell Metabolism 2014, Nat Commun2018, 2022, EMBO 2023, EMBO Rep 2023).