Glucagon gene expression in the endocrine pancreas: the role of the transcription factor Pax6 in <i>α</i>‐cell differentiation, glucagon biosynthesis and secretion

Gosmain, Yvan; Cheyssac, Claire; Masson, M; Dibner, Charna; Philippe, Jacques

doi:10.1111/j.1463-1326.2011.01445.x

Cited by 61 publications

(57 citation statements)

References 51 publications

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“…Paired box 6 (PAX6) is a highly conserved transcription regulatory factor involved in multiple biological processes, including embryogenesis, cell differentiation, biosynthesis and cell motility (1,2). Accumulating evidence has demonstrated that PAX6 is crucial in the development of the central nervous system (3).…”

Section: Introductionmentioning

confidence: 99%

PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells

Cheng

Cao²,

Chen

et al. 2014

Molecular Medicine Reports

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Abstract. Paired box 6 (PAX6), a highly conserved transcription factor, is important in glioma. However, the molecular mechanisms involved remain unclear. The present study demonstrated that the expression of PAX6 was significantly reduced with the malignancy of glioma and also identified PAX6 as a novel target of microRNA (miR)-335, which was significantly upregulated in glioma. The inhibition of miR-335 increased the protein expression of PAX6, whereas the upregulation of miR-335 suppressed its expression in human glioma U251 and U87 cells. Furthermore, upregulation of miR-335 promoted U251 cell proliferation, colony formation and invasion, which was reversed by the overexpression of PAX6. Furthermore, the present study demonstrated that the effect of miR-335 on U251 cell invasion was via the modulation of matrix metalloproteinase (MMP)-2 and MMP-9 expression by targeting PAX6. In conclusion, the present study demonstrated that PAX6, as a novel target of miR-335, has an anti-oncogenic function in glioma, and thus PAX6 may serve as a therapeutic target for glioma.

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Section: Introductionmentioning

confidence: 99%

PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells

Cheng

Cao²,

Chen

et al. 2014

Molecular Medicine Reports

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“…Here we review aspects of a-cell specification, differentiation, and maturation. For a more detailed review on a-cell physiology and glucagon regulation please see Gromada et al (2007) and Gosmain et al (2011).…”

Section: Islet A-cell Developmentmentioning

confidence: 99%

“…4A) (Gosmain et al 2011). Pax6 mutants lack a cells, and have reduced glucagon expression and MafB expression, another regulator of glucagon expression that is selectively expressed in adult a cells in mice (Artner et al 2006;Nishimura et al 2006Nishimura et al , 2008Gosmain et al 2010).…”

Section: Islet A-cell Developmentmentioning

confidence: 99%

Deconstructing Pancreas Developmental Biology

Benitez¹,

Goodyer²,

Kim³

2012

Cold Spring Harbor Perspectives in Biology

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SUMMARYThe relentless nature and increasing prevalence of human pancreatic diseases, in particular, diabetes mellitus and adenocarcinoma, has motivated further understanding of pancreas organogenesis. The pancreas is a multifunctional organ whose epithelial cells govern a diversity of physiologically vital endocrine and exocrine functions. The mechanisms governing the birth, differentiation, morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine components in the pancreas have been discovered recently with increasing tempo. This includes recent studies unveiling mechanisms permitting unexpected flexibility in the developmental potential of immature and mature pancreatic cell subsets, including the ability to interconvert fates. In this article, we describe how classical cell biology, genetic analysis, lineage tracing, and embryological investigations are being complemented by powerful modern methods including epigenetic analysis, time-lapse imaging, and flow cytometrybased cell purification to dissect fundamental processes of pancreas development.

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“…The promoter consists of a region comprising the regulatory sequences G1 and G4 while the remaining sequences are part of the enhancer regions. Numerous transcription factors are involved in the control of glucagon expression such as LIM-homeobox transcription factor islet-1 (Isl1), paired box gene 6 (Pax6), musculoaponeurotic fibrosarcoma oncogene homolog (Mafs), forkhead box protein A1 (Foxa1) and forkhead box protein A2 (Foxa2) among others (81,82) . The transcription of the preproglucagon gene results in a peptide of 160 amino acids.…”

Section: Glucagon Synthesismentioning

confidence: 99%

Nutrient regulation of glucagon secretion: involvement in metabolism and diabetes

et al. 2014

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Glucose homeostasis is precisely regulated by glucagon and insulin, which are released by pancreatic a-and b-cells, respectively. While b-cells have been the focus of intense research, less is known about a-cell function and the actions of glucagon. In recent years, the study of this endocrine cell type has experienced a renewed drive. The present review contains a summary of established concepts as well as new information about the regulation of a-cells by glucose, amino acids, fatty acids and other nutrients, focusing especially on glucagon release, glucagon synthesis and a-cell survival. We have also discussed the role of glucagon in glucose homeostasis and in energy and lipid metabolism as well as its potential as a modulator of food intake and body weight. In addition to the well-established action on the liver, we discuss the effects of glucagon in other organs, where the glucagon receptor is expressed. These tissues include the heart, kidneys, adipose tissue, brain, small intestine and the gustatory epithelium. Alterations in a-cell function and abnormal glucagon concentrations are present in diabetes and are thought to aggravate the hyperglycaemic state of diabetic patients. In this respect, several experimental approaches in diabetic models have shown important beneficial results in improving hyperglycaemia after the modulation of glucagon secretion or action. Moreover, glucagon receptor agonism has also been used as a therapeutic strategy to treat obesity.

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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

Cited by 61 publications

References 51 publications

PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells

PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells

Deconstructing Pancreas Developmental Biology

Nutrient regulation of glucagon secretion: involvement in metabolism and diabetes

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