Pax 4 and 6 regulate gastrointestinal endocrine cell development

Larsson, Lars; St‐Onge, Luc; Hougaard, David M.; Sosa–Pineda, Beatriz; Gruß, Peter

doi:10.1016/s0925-4773(98)00182-8

Cited by 128 publications

(104 citation statements)

References 23 publications

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“…Pax-6 Ϫ/Ϫ mice exhibit reduced numbers of duodenal gastrointenstinal polypeptide (GIP) cells and decreased numbers of gastric cells immunopositive for gastrin and somatostatin (40). Analysis of endocrine cell populations in the gut of Sey neu mice expressing a dominant negative Pax-6 protein revealed almost complete absence of enteroendocrine cells containing GLP-1 or GLP-2 immunopositivity and a marked decrease in the levels of proglucagon mRNA transcripts in the small and large intestine (19).…”

Section: Discussionmentioning

confidence: 99%

Pax-6 Activates Endogenous Proglucagon Gene Expression in the Rodent Gastrointestinal Epithelium

et al. 2003

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Section: Discussionmentioning

confidence: 99%

Pax-6 Activates Endogenous Proglucagon Gene Expression in the Rodent Gastrointestinal Epithelium

et al. 2003

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“…Enteroendocrine and pancreatic endocrine development are controlled by the group IV members, Pax-4 and Pax-6. Pax-4 is essential for pancreatic ␤ and ␦ cells, duodenal and jejunal secretin-positive cells, as well as serotonin-and somatostatin-producing cells in the stomach (7,8). In contrast, Pax-6 is required for the development of all pancreatic endocrine cells, duodenal GIP-positive cells, and gastrin-and somatostatin-producing cells in the stomach (8 -10).…”

mentioning

confidence: 99%

The Paired Homeodomain Transcription Factor Pax-2 Is Expressed in the Endocrine Pancreas and Transactivates the Glucagon Gene Promoter

Ritz-Laser¹,

Estreicher²,

Gauthier³

et al. 2000

Journal of Biological Chemistry

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Glucagon gene expression is controlled by at least four DNA elements within the promoter; G2, G3, and G4 confer islet-specific expression, while G1 restricts glucagon transcription to ␣ cells. Two islet-specific complexes are formed on G3, the insulin-responsive element of the glucagon gene; one of these corresponds to the paired homeodomain protein Pax-6, a major glucagon gene transactivator that plays a crucial role in ␣ cell development. We describe here the identification of the second complex as Pax-2, another member of the paired box family. Pax-2 is known to be crucial for the development of the urogenital tract and of the central nervous system, but its presence in the endocrine pancreas has not been reported. We detected Pax-2 gene expression by RT-PCR; in islets, Pax-2 is present as two alternative splicing isoforms, Pax-2A and Pax-2B, whereas in the glucagon-and insulin-producing cell lines ␣TC1 and Min6, a distinct isoform, Pax-2D2, is found in addition to Pax-2B. Both islet-specific isoforms bind to the enhancer element G3 and to the ␣-specific promoter element G1 that also interacts with Pax-6. Pax-2A and Pax-2B dose-dependently activate transcription from the G3 and the G1 elements both in heterologous and in glucagon-producing cells. Our data indicate that Pax-2 is the third paired domain protein present in the endocrine pancreas and that one of its roles may be the regulation of glucagon gene expression.

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“…The number of GIP-expressing cells in the duodenum of Pax6-deficient mice is reduced. 157 Pax6 is crucial for proglucagon gene expression in intestinal epithelium. It is expressed in intestinal EECs and binds to G1 and G3 elements in the proglucagon promoter to activate its transcription.…”

Section: Cell Differentiation and Intestinal Adaptationmentioning

confidence: 99%

Isolated ileal interposition in enteroendocrine L cells differentiation

Cardia¹,

Azevedo²,

Azevedo³

et al. 2011

Nature Precedings

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INTRODUCTION:Due to the progressive nature of type 2 diabetes, its complexity and drug treatment perpetuity, there is currently a search for surgical procedures that can promote euglycemia also in non-obese patients. Diabetic patients glycemic control can be achieved by increasing the blood concentration of GLP-1, a hormone produced by L cells that are more densely concentrated in the terminal ileum. Early and extended improvement of diabetes in patients submitted to bariatric surgeries awakened the necessity of investigating the isolated ileal interposition as surgical alternative for the treatment of diabetes. The interposition of this ileal segment to a more anterior region (proximal jejunum) can promote a greater stimulation of the L cells by poorly digested food, increasing the production of GLP-1 and reflecting on glycemic control. However, in order to consolidate the ileal interposition as a surgical treatment of diabetes it is necessary that the interposed ileum keep the same differentiation rate into L cells for a long period to justify the intervention. AIMS:To investigate the isolated ileal interposition influence on the differentiation of intestinal precursor cells into enteroendocrine L cells over time. METHODS:Twelve 12-week-old male Wistar rats (Rattus norvegicus albinus) of the WAB strain (heterogeneous) will be used. All animals will receive a high-calorie, high-fat diet for 16 weeks or more until they develop glucose dysmetabolism confirmed by glycemic test. They will be divided into two groups of 10 animals each: the isolated ileal interposition group (GI) and the control group (GC), comprising animals that will not be submitted to any surgical intervention.Blood samples will be collected under anesthesia at the weeks 12, 26, 36 and 44 for the determination of serum levels of glucose, insulin, GLP-1, glucagon, C-peptide and glycosilated hemoglobin. The insulin tolerance test will be performed and insulin resistance will be calculated. For the comparative analysis of the ileal precursor cells differentiation into enteroendocrine cells among the two groups, the following intestinal fragments will be collected after euthanasia: interposed ileum and remaining ileum from GI, jejunum and ileum from GC. These fragments will be analyzed by imunofluorescence and also by Real Time PCR using PCR Arrays for target genes including the main ones related to stem cell, stem cell singnalling, diabetes, Wnt and Notch signaling pathways and other genes and pathways involved in the differentiation of intestinal precursor cells into enteroendocrine cells, especially GLP-1-producing L cells that play important role in euglycemia.

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Pax 4 and 6 regulate gastrointestinal endocrine cell development

Cited by 128 publications

References 23 publications

Pax-6 Activates Endogenous Proglucagon Gene Expression in the Rodent Gastrointestinal Epithelium

Pax-6 Activates Endogenous Proglucagon Gene Expression in the Rodent Gastrointestinal Epithelium

The Paired Homeodomain Transcription Factor Pax-2 Is Expressed in the Endocrine Pancreas and Transactivates the Glucagon Gene Promoter

Isolated ileal interposition in enteroendocrine L cells differentiation

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