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PMID:22649445

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Citation

Dames, P, Weise, M, Puff, R, Göke, B, Parhofer, KG, Seissler, J and Lechner, A (2012) Suppression of the nuclear factor Eny2 increases insulin secretion in poorly functioning INS-1E insulinoma cells. Exp Diabetes Res 2012:460869

Abstract

Eny2, the mammalian ortholog of yeast Sus1 and drosophila E(y)2, is a nuclear factor that participates in several steps of gene transcription and in mRNA export. We had previously found that Eny2 expression changes in mouse pancreatic islets during the metabolic adaptation to pregnancy. We therefore hypothesized that the protein contributes to the regulation of islet endocrine cell function and tested this hypothesis in rat INS-1E insulinoma cells. Overexpression of Eny2 had no effect but siRNA-mediated knockdown of Eny2 resulted in markedly increased glucose and exendin-4-induced insulin secretion from otherwise poorly glucose-responsive INS-1E cells. Insulin content, cellular viability, and the expression levels of several key components of glucose sensing remained unchanged; however glucose-dependent cellular metabolism was higher after Eny2 knockdown. Suppression of Eny2 enhanced the intracellular incretin signal downstream of cAMP. The use of specific cAMP analogues and pathway inhibitors primarily implicated the PKA and to a lesser extent the EPAC pathway. In summary, we identified a potential link between the nuclear protein Eny2 and insulin secretion. Suppression of Eny2 resulted in increased glucose and incretin-induced insulin release from a poorly glucose-responsive INS-1E subline. Whether these findings extend to other experimental conditions or to in vivo physiology needs to be determined in further studies.

Links

PubMed PMC3357931 Online version:10.1155/2012/460869

Keywords

Animals; Cell Line; Cell Nucleus/metabolism; Cyclic AMP/metabolism; Cyclic AMP-Dependent Protein Kinases/metabolism; Female; Glucose/metabolism; Insulin/secretion; Insulinoma/metabolism; Mice; Mice, Inbred C57BL; Peptides/metabolism; RNA, Messenger/metabolism; Rats; Transcription Factors/metabolism; Venoms/metabolism

Significance

Annotations

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

RAT:D3ZWF5

involved_in

GO:0061179: negative regulation of insulin secretion involved in cellular response to glucose stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ENY2

GO:0006006: glucose metabolic process

ECO:0000315:

P

Figure 3(d) - Glucose metabolism as measured by an MTT assay Increased after ENY2 knockdown.

complete
CACAO 11609

MOUSE:ENY2

GO:0061179: negative regulation of insulin secretion involved in cellular response to glucose stimulus

ECO:0000315:

P

Figure 3(e) - Insulin secretion increases in response to Tolbutamide stimulus after ENY2 supression.

complete
CACAO 11619

MOUSE:ENY2

GO:0035774: positive regulation of insulin secretion involved in cellular response to glucose stimulus

ECO:0000315:

P

Figure 4(c) - Insulin secretion increased in response to stimulation with 50nmol/l exendin-4 and 10μmol/1 forskolin.

complete
CACAO 11620

Notes

See also

References

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