Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth.

摘要: Mutations in the genes encoding transcriptional regulators HNF1beta (TCF2), HNF1alpha (TCF1), and HNF4alpha cause autosomal dominant diabetes (also known as maturity-onset of young). Herein, we review what have learnt during recent years concerning functions these developing adult pancreas. Mouse studies revealed that is a critical regulator network controls specification, growth, differentiation embryonic mutations humans accordingly often pancreas hypoplasia. By contrast, been shown to regulate function differentiated beta-cells. patients thus decreased glucose-induced insulin secretion leads progressive form diabetes. paradoxically also utero neonatal hyperinsulinism, which later evolves secretion. Recent show Hnf4alpha deficiency mice causes not only abnormal secretion, but an impairment expansion beta-cell mass normally occurs pregnancy. In line with this finding, present data Hnf1alpha-/- beta-cells expressing SV40 large T antigen severe proliferation failure tumours. Collectively, findings implicate organogenesis differentiation, whereas primarily both growth islet