title: Glucagon gene expression in the endocrine pancreas: the role of the transcription factor Pax6 in α-cell differentiation, glucagon biosynthesis and secretion.
abstract: The glucagon gene is expressed in α-cells of the pancreas, L cells of the intestine and the hypothalamus. The determinants of the α-cell-specific expression of the glucagon gene are not fully characterized, although Arx, Pax6 and Foxa2 are critical for α-cell differentiation and glucagon gene expression; in addition, the absence of the β-cell-specific transcription factors Pdx1, Pax4 and Nkx6.1 may allow for the glucagon gene to be expressed. Pax6, along with cMaf and MafB, binds to the DNA control element G(1) which confers α-cell specificity to the promoter and to G(3) and potently activates glucagon gene transcription. In addition, to its direct role on the transcription of the glucagon gene, Pax6 controls several transcription factors involved in the activation of the glucagon gene such as cMaf, MafB and NeuroD1/Beta2 as well as different steps of glucagon biosynthesis and secretion. We conclude that Pax6 independently of Arx and Foxa2 is critical for α-cell function by coordinating glucagon gene expression as well as glucagon biosynthesis and secretion.
authors.affiliation: Division of Endocrinology, Diabetes and Nutrition, University Hospital Geneva, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland. yvan.gosmain@hcuge.ch
authors.forename: Y
authors.initials: Y
authors.lastname: Gosmain
authors.forename: C
authors.initials: C
authors.lastname: Cheyssac
authors.forename: M
authors.initials: M
authors.lastname: Heddad Masson
authors.forename: C
authors.initials: C
authors.lastname: Dibner
authors.forename: J
authors.initials: J
authors.lastname: Philippe
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005934:Glucagon / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C000605733:Pax6 protein, rat; D012097:Repressor Proteins; D014157:Transcription Factors; D005934:Glucagon