Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function
| Autor: | Isabella Artner, Elvira Ganic, Malin Fex, Marcus Winkler, Hedvig Bennet, Jenny Johansson, Ulrike A. Nuber, Magdalena Mazur, Jesper K. Colberg |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Blood Glucose
Transcriptional Activation medicine.medical_specialty endocrine system PAX6 Transcription Factor Endocrinology Diabetes and Metabolism Biology Pigment cell differentiation Islets of Langerhans Mice Downregulation and upregulation Internal medicine Insulin-Secreting Cells Insulin Secretion Internal Medicine medicine STXBP1 Glucose homeostasis Animals Insulin Paired Box Transcription Factors Eye Proteins Transcription factor Original Research Homeodomain Proteins Microphthalmia-Associated Transcription Factor integumentary system Microphthalmia-associated transcription factor Cell biology body regions Repressor Proteins Endocrinology Islet Studies Mutation PAX4 PAX6 sense organs |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Precise regulation of β-cell function is crucial for maintaining blood glucose homeostasis. Pax6 is an essential regulator of β-cell–specific factors like insulin and Glut2. Studies in the developing 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 postnatal 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 β-cell mass in adult mice. Mutant β-cells secrete more insulin in response to glucose than wild-type cells, suggesting that Mitf is involved in regulating β-cell function. In fact, the transcription of genes critical for maintaining glucose homeostasis (insulin and Glut2) and β-cell formation and function (Pax4 and Pax6) is significantly upregulated in Mitf mutant islets. The increased Pax6 expression may cause the improved β-cell function observed in Mitf mutant animals, as it activates insulin and Glut2 transcription. Chromatin immunoprecipitation analysis shows that Mitf binds to Pax4 and Pax6 regulatory regions, suggesting that Mitf represses their transcription in wild-type β-cells. We demonstrate that Mitf directly regulates Pax6 transcription and controls β-cell function. |
| Databáze: | OpenAIRE |
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