Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An important regulatory element (designated FP330-3') of the ALDH2 promoter mediates activation by hepatocyte nuclear factor 4 (HNF4). This activation of promoter constructs containing this element by HNF4 was reduced by nearly half by 8-Br-cAMP in H4IIEC3 cells, an effect that was blocked by inhibitors of protein kinase A (PKA). Cotransfection assays showed that COUP-TF I, ARP-1, or PPARdelta suppressed the ability of HNF4 to activate the reporter. The repression was potentiated by 8-Br-cAMP. Electrophoretic mobility shift assays revealed that treatment of hepatoma cells or cultured rat hepatocytes with 1 mM 8-Br-cAMP or glucagon reduced binding of FP330-3' by HNF4 by half. In vitro phosphorylation of HNF4 by PKA decreased binding to FP330-3'. Fasting reduced the ALDH2 protein level in liver and kidney, two tissues expressing HNF4, but not heart. These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting.
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PMID:Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4: inhibition by cyclic AMP and COUP transcription factors. 1181 51

In mammals, the COUP-TF-family consisting of two structurally related proteins, COUP-TFI and COUP-TFII belongs to the orphan member of the steroid/thyroid hormone receptor superfamily. In an attempt to gain insights into the role of COUP-TFII, we examined developmental expression pattern of the mouse COUP-TFII focusing our studies on endoderm-derived tissues, pancreas and liver in particular. Independent lines of transgenic mice expressing Escherichia coli beta-galactosidase driven by the COUP-TFII promoter were generated. Embryonic expression of the beta-gal protein at day 9 of gestation was detected in the notochord, the ventral neural tube and, interestingly, in the gut endoderm, a site where COUP-TFII has not been detected previously. Between 9.5 and 11.5 dpc, beta-gal expression pattern that was established earlier persisted and sections revealed a staining of the common atrial chamber of the heart. At 15.5 dpc, beta-gal activity was found in all endoderm-derived tissues. We found that COUP-TFII mRNA and protein were present in fetal and adult hepatocytes. Finally, COUP-TFII expression was detected in pancreas, as judged by co-expression of the beta-gal in some of the glucagon and PDX1 positive-cells at 12.5 dpc and co-expression with insulin positive-cells at 15.5 dpc. In adult pancreas, COUP-TFII protein was present in the endocrine islet cells.
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PMID:Expression of COUP-TFII in metabolic tissues during development. 1238 58

Islet neogenesis, or the differentiation of islet cells from precursor cells, is seen in vitro and in vivo both embryonically and after birth. However, little is known about the differentiation pathways during embryonic development for human pancreas. Our previously reported in vitro generation of islets from human pancreatic tissue provides a unique system to identify potential markers of neogenesis and to determine the molecular mechanisms underlying this process. To this end, we analyzed the gene expression profiles of three different stages during in vitro islet generation: the Initially Adherent, Expanded, and Differentiated stages. Samples from four human pancreases were hybridized to Affymetrix U95A GeneChips, and data analyzed using GeneSpring 7.0/9.0 software. Using scatter plots we selected genes with a 2-fold or greater differential expression. Of the 12,000 genes/ESTs present on these arrays, 295 genes including 38 acinar-enriched genes were selectively lost during the progression from the Initially Adherent stage to the Expanded stage; 468 genes were increased in this progression to Expanded tissue; and 529 genes had a two-fold greater expression in the Differentiated stage than in the Expanded tissue. Besides the expected increases in insulin, glucagon, and duct markers (mucin 6, aquaporin 1 and 5), the beta cell auto-antigen IA-2/phogrin was increased 5-fold in Differentiated. In addition, developmentally important pathways, including notch/jagged, Wnt/frizzled, TGFbeta superfamily (follistatin, BMPs, and SMADs), and retinoic acid (COUP-TFI, CRABP1, 2, and RAIG1) were differentially regulated during the expansion/differentiation. Two putative markers for islet precursor cells, UCHL1/PGP9.5 and DMBT1, were enhanced during the progression to differentiated cells, but only the latter could be a marker of islet precursor cells. We suggest that appropriate manipulation of these differentiation-associated pathways will enhance the efficiency of differentiation of insulin-producing beta-cells in this in vitro model.
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PMID:Developmental pathways during in vitro progression of human islet neogenesis. 1928 73