Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucagon and glucagon-like peptide-1 (GLP-1) are important regulators of glucose homeostasis, and both are involved in regulating pancreatic islet hormone secretion. Since the sensitivity of the endocrine pancreas to regulatory hormones can be influenced by their receptor number, we have examined the regulation of glucagon receptor and GLP-1 receptor messenger RNA (mRNA) expression in cultured rat pancreatic islets by various factors, including glucose, cAMP, and glucocorticoids. By ribonuclease protection assay we have demonstrated the expression of both glucagon and GLP-1 receptor mRNA in cultured rat islets. We observed a dose-dependent increase in glucagon receptor mRNA expression with increasing glucose concentrations: an approximately 3-fold increase in glucagon receptor mRNA in islets cultured in 22 mM glucose as compared to 3.5 mM glucose. GLP-1 receptor mRNA levels, on the other hand, were not affected by culturing the islets in low glucose concentrations; however, a small, but significant, decrease in GLP-1 receptor mRNA levels was detected when islets were cultured in 20 mM glucose. Forskolin and 3-isobuty-1-methylxanthine, which increase intracellular cAMP levels, caused a 75% reduction in glucagon receptor mRNA expression. Somatostatin 14 and 28, both of which can inhibit intracellular cAMP production, stimulated glucagon receptor mRNA expression by 40% and 75%, respectively. GLP-1 receptor mRNA levels remained unchanged under all conditions that altered intracellular cAMP levels. Finally, in islets cultured in the presence of 10 nM dexamethasone an approximately 50% decrease in both glucagon and GLP-1 receptor mRNA expression was observed. These results indicate that the expression of glucagon and GLP-1 receptor mRNA is differentially regulated in rat pancreatic islets and suggest that regulation of receptor mRNA expression may be an important mechanism for controlling the sensitivity of the islets to glucagon and GLP-1.
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PMID:Regulation of glucagon and glucagon-like peptide-1 receptor messenger ribonucleic acid expression in cultured rat pancreatic islets by glucose, cyclic adenosine 3',5'-monophosphate, and glucocorticoids. 753 5

Glucagon, the pancreatic hormone secreted in response to hypoglycemia, is a key regulator of hepatic glucose production. Since the number of specific glucagon receptors expressed on the cell surface affects the sensitivity of the liver to glucagon, we have examined the regulation of glucagon receptor mRNA levels in cultured primary rat hepatocytes. By ribonuclease protection assay we have identified glucose and intracellular cAMP as regulators of glucagon receptor mRNA expression in cultured rat hepatocytes. We observed a concentration-dependent increase in glucagon receptor mRNA expression when hepatocytes were cultured in the presence of increasing glucose. A 2-fold induction in glucagon receptor mRNA levels was obtained in hepatocytes cultured for 24 h with 22.5 mM glucose as compared with 5.5 mM glucose. Factors such as 3-isobutyl-1-methylxanthine (IBMX), isoproterenol, and forskolin, which are known to raise intracellular cAMP levels, all caused a reduction in glucagon receptor mRNA expression. IBMX alone, IBMX together with isoproterenol, and forskolin reduced glucagon receptor mRNA expression to approximately 25, 10, and 50%, respectively. Glucagon was found to dose dependently decrease glucagon receptor mRNA expression in the hepatocytes with an approximately 70% reduction in response to 100 nM glucagon. Finally, we observed a marked reduction in the number of glucagon binding sites (35% of control) after hepatocytes were cultured with the combination of IBMX and isoproterenol. These results indicate that hepatic glucagon receptor mRNA levels can be regulated by glucose and intracellular cAMP and that this is also reflected at the protein level. Furthermore, the observed effects of cAMP and glucagon suggest that this may be a means by which glucagon can down-regulate its own receptor expression.
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PMID:Regulation of glucagon receptor mRNA in cultured primary rat hepatocytes by glucose and cAMP. 754 Oct 48

Glucagon gene transcription in the endocrine pancreas is regulated by at least four cis-acting DNA control elements. We showed previously that G1 is critical for alpha cell-specific expression. G1 contains three AT-rich sequences important for promoter function, which represent candidate binding sites for homeodomain transcription factors. Performing reverse transcription-polymerase chain reaction amplifications with degenerate oligonucleotide primers homologous to the Antennapedia homeobox, cDNA clones corresponding to the caudal-related gene cdx-2/3 were predominantly obtained from glucagon-producing cells and primary non-beta cells. From RNase protection and polymerase chain reaction analyses, cdx-2/3 turned out to be the only caudal-related gene that is expressed at significant levels in cells of the endocrine pancreas. Cdx-2/3 binds with high affinity to an AT-rich motif of G1, which matches the consensus binding site of caudal-related proteins. In the glucagon-producing hamster cell line InR1G9, Cdx-2/3 is a subunit of complex B3 formed on G1. Alternative splicing generates two cdx-2/3 transcripts in islet cells, coding for a full-length protein and an amino-terminally truncated isoform. Although both isoforms bind G1 with similar affinity, only the full-length Cdx-2/3 A protein activates glucagon gene transcription in non-glucagon-producing cells, transcriptional activation being dose-dependent. We therefore conclude that the caudal-related gene cdx-2/3 is implicated in the transcriptional control of glucagon gene expression in the alpha cells of the islets of Langerhans.
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PMID:The caudal-related homeodomain protein Cdx-2/3 regulates glucagon gene expression in islet cells. 891 May 49