Expression of these hormones is crucial for maintaining glucose homeostasis, as glucagon released from α-cells stimulates the mobilization of glucose through gluconeogenesis and glycogenolysis to prevent hypoglycemia, while insulin released from β-cells promotes glucose storage. Islet-enriched transcription factors have been shown to play fundamental roles in pancreas development and function, especially those linked to endocrine cell-specific expression of the hormones glucagon and insulin (reviewed by Sander & German 1997, Servitja & Ferrer 2004). Collectively, these results demonstrate a unique ability for MafA to independently activate Insulin transcription.Įncouraging results obtained in treating type 1 diabetes by islet transplantation have stimulated efforts to develop an abundant source of functional insulin-producing cells ( Shapiro et al. MafA was also bound to Insulin and Glucagon transcriptional control sequences in mouse embryonic pancreas and β-cell lines. Analysis of chimeric proteins of MafA and MafB demonstrated that chick Insulin activation depended on sequences within the MafA C-terminal DNA-binding domain. Co-electroporation of MafA with the Ngn3 transcription factor resulted in the development of more organized cell clusters containing both insulin- and glucagon-producing cells. Ectopic expression of MafA, but not MafB, promoted Insulin production however, neither MafA nor MafB were capable of inducing Glucagon. Here, we analyzed whether these factors were sufficient to induce insulin + and/or glucagon + cell formation within embryonic endoderm using the chick in ovo electroporation assay. However, only MafA over-expression selectively induced endogenous Insulin mRNA production in cell line-based assays, while MafB specifically promoted Glucagon expression. MafB −/− animals are also deficient in insulin + and glucagon + cell production during embryogenesis. MafA and MafB are co-expressed in insulin +β-cells during embryogenesis, while in the adult pancreas only MafA is produced in β-cells and MafB in glucagon +α-cells. The closely related MafA and MafB transcription factors are both key mammalian β-cell regulators. As successful generation of insulin-producing cells could be used for diabetes treatment, a concerted effort is being made to understand the molecular programs underlying islet β-cell formation and function.
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