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

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Published in Diabetes, Obesity and Metabolism. 2011, vol. 13 Suppl 1, p. 31-8
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.
Keywords AnimalsCell DifferentiationDiabetes Mellitus, ExperimentalEye Proteins/genetics/metabolismGene Expression RegulationGlucagon/biosynthesis/genetics/secretionGlucagon-Secreting Cells/cytology/metabolismHomeodomain Proteins/genetics/metabolismMicePaired Box Transcription Factors/genetics/metabolismRatsRepressor Proteins/genetics/metabolismTranscription Factors
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PMID: 21824254
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Article (Published version) (841 Kb) - document accessible for UNIGE members only Limited access to UNIGE
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Research group Diabète et régulation des gènes (36)
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GOSMAIN, Yvan et al. Glucagon gene expression in the endocrine pancreas: the role of the transcription factor Pax6 in α-cell differentiation, glucagon biosynthesis and secretion. In: Diabetes, Obesity and Metabolism, 2011, vol. 13 Suppl 1, p. 31-8. https://archive-ouverte.unige.ch/unige:25626

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Deposited on : 2013-01-17

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