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PMID:11250924

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Citation

Fernandez-Mejia, C, Vega-Allende, J, Rojas-Ochoa, A, Rodriguez-Dorantes, M, Romero-Navarro, G, Matschinsky, FM, Wang, J and German, MS (2001) Cyclic adenosine 3',5'-monophosphate increases pancreatic glucokinase activity and gene expression. Endocrinology 142:1448-52

Abstract

Comparison of the pancreatic and hepatic glucokinase gene transcripts reveals tissue-specific control of expression and the existence of two distinct promoters in a single glucokinase gene. The existence of alternate promoters suggests that separate factors regulate glucokinase transcription in the two tissues. Hepatic glucokinase expression has been shown to be repressed by cAMP; however, in the pancreatic beta-cell it is unlikely that cAMP represses glucokinase activity, as cAMP is known to positively affect glucose-induced insulin secretion, a process that in mature islets requires pancreatic glucokinase activity. In this work we demonstrate that cAMP indeed has a stimulatory effect on pancreatic glucokinase. The cyclic nucleotide stimulates pancreatic glucokinase activity after 3-h incubation, and maximal effects are observed after 6 and 12 h of treatment. Using the bDNA assay, a sensitive signal amplification technique, we detected relative increases in glucokinase messenger RNA levels of 40.5 +/- 7.5% after 3-h incubation with cAMP. This stimulatory effect was increased to 106.3 +/- 22% after 6-h incubation and sustained up to 12 h of incubation. Inhibition of gene transcription by actinomycin D abolishes cAMP-induced glucokinase activity. In transfected fetal islets, cAMP increased the activity of the -1000 bp rat glucokinase promoter by 60 +/- 6%. These data demonstrate that cAMP has a stimulatory effect on pancreatic glucokinase gene expression and that the nucleotide has opposite effects on pancreatic and hepatic glucokinase, supporting the concept that glucokinase transcription in the liver and that in the beta-cell differ.

Links

PubMed

Keywords

Animals; Cyclic AMP/pharmacology; Dactinomycin/pharmacology; Female; Fetus/metabolism; Gene Expression Regulation, Enzymologic/drug effects; Glucokinase/genetics; Glucokinase/metabolism; Nucleic Acid Synthesis Inhibitors/pharmacology; Pancreas/enzymology; Plasmids/genetics; Pregnancy; Promoter Regions, Genetic/genetics; RNA, Messenger/biosynthesis; Rats; Rats, Wistar; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:HXK4

enables

GO:0004340: glucokinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:HXK4

involved_in

GO:0001678: cellular glucose homeostasis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

RAT:HXK4

involved_in

GO:0019932: second-messenger-mediated signaling

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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