Glucagon gene expression in the endocrine pancreas: the role of the transcription factor Pax6 in α-cell differentiation, glucagon biosynthesis and secretion

Autor: Charna Dibner, Claire Cheyssac, Yvan Gosmain, M. Heddad Masson, Jacques Philippe
Jazyk: angličtina
Rok vydání: 2011
Předmět:
medicine.medical_specialty
endocrine system
PAX6 Transcription Factor
Endocrinology
Diabetes and Metabolism
Biology
Glucagon
Diabetes Mellitus
Experimental
03 medical and health sciences
Mice
0302 clinical medicine
Endocrinology
Glucagon-Secreting Cells/cytology/metabolism
Internal medicine
Glucagon/biosynthesis/genetics/secretion
Internal Medicine
medicine
Paired Box Transcription Factors
Animals
Homeodomain Proteins/genetics/metabolism
Eye Proteins
Glucagon-like peptide 1 receptor
030304 developmental biology
Regulation of gene expression
Homeodomain Proteins
ddc:616
Repressor Proteins/genetics/metabolism
0303 health sciences
Eye Proteins/genetics/metabolism
digestive
oral
and skin physiology
Cell Differentiation
Rats
Repressor Proteins
Paired Box Transcription Factors/genetics/metabolism
Gene Expression Regulation
MAFB
Glucagon-Secreting Cells
NEUROD1
PDX1
PAX4
Glucagon receptor family
030217 neurology & neurosurgery
hormones
hormone substitutes
and hormone antagonists
Transcription Factors
Zdroj: Diabetes, Obesity and Metabolism, Vol. 13 Suppl 1 (2011) pp. 31-8
Diabetes obesity & metabolism
ISSN: 1462-8902
Popis: 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.
Databáze: OpenAIRE
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