Microphthalmia Transcription Factor Regulates Pancreatic b-Cell Function

Precise regulation of b-cell function is crucial for maintaining blood glucose homeostasis. Pax6 is an essential regulator of b-cell–specific factors like insulin and Glut2. Studies in the de-veloping eye suggest that Pax6 interacts with Mitf to regulate pigment cell differentiation. Here, we show that Mitf, like Pax6, is expressed in all pancreatic endocrine cells during mouse post-natal development and in the adult islet. A Mitf loss-of-function mutation results in improved glucose tolerance and enhanced insulin secretion but no increase in b-cell mass in adult mice. Mutant b-cells secrete more insulin in response to glucose than wild-type cells, suggesting that Mitf is involved in regulating b-cell function. In fact, the transcription of genes critical for maintain-ing glucose homeostasis (insulin and Glut2) and b-cell formation and function (Pax4 and Pax6) is significantly upregulated in Mitf mutant islets. The increased Pax6 expression may cause the im