RGD Reference Report - Down-regulation of expression and function of nucleoside diphosphate kinase in insulin-secreting beta-cells under in vitro conditions of glucolipotoxicity.

General

Down-regulation of expression and function of nucleoside diphosphate kinase in insulin-secreting beta-cells under in vitro conditions of glucolipotoxicity.
Authors:	Veluthakal, R Suresh, MV Kowluru, A
Citation:	Veluthakal R, etal., Mol Cell Biochem. 2009 Sep;329(1-2):121-9. Epub 2009 Apr 15.
RGD ID:	5132883
Pubmed:	PMID:19367376 (View Abstract at PubMed)
DOI:	DOI:10.1007/s11010-009-0113-6 (Journal Full-text)
Previously, we reported a significant reduction in expression and the activity of nucleoside diphosphate kinase (NDP kinase) in islets derived from the Goto-Kakizaki rat (GK rat), an animal model for type 2 diabetes. Herein, we examined the effects of chronic exposure of insulin-secreting beta-(INS 832/13) cells to high glucose (a model for glucotoxicity), palmitate (a model for lipotoxicity), or glucose plus palmitate (a model for glucolipotoxicity) on the expression and activity of nm23-H1 (NDP kinase A) and nm23-H2 (NDP kinase B). Our findings indicate a marked reduction in the expression of both nm23-H1 and nm23-H2 and the associated NDP kinase activity under each of these conditions. A cell-permeable analog of ceramide (CER) also mimicked the effects of palmitate in significantly reducing the expression of nm23-H1 and nm23-H2 and NDP kinase activity in these cells. These findings suggest that de novo generation of intracellular CER from palmitate might represent at least one of the signaling steps involved in lipid-induced effects on NDP kinase expression and function in beta-cells. Based on these data, we conclude that glucolipotoxic conditions significantly impair expression and function of NDP kinase in pancreatic beta-cells. Potential significance of these findings, specifically at the level of abnormal G-protein activation and impaired insulin secretion under glucolipotoxic conditions is discussed.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Nme1	Rat	cellular response to fatty acid		IEP		palmitate	RGD
Nme2	Rat	cellular response to fatty acid		IEP		palmitate	RGD
Nme1	Rat	cellular response to glucose stimulus		IEP			RGD
Nme2	Rat	cellular response to glucose stimulus		IEP			RGD

Objects Annotated

Genes (Rattus norvegicus)

Nme1 (NME/NM23 nucleoside diphosphate kinase 1)

Nme2 (NME/NM23 nucleoside diphosphate kinase 2)

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Down-regulation of expression and function of nucleoside diphosphate kinase in insulin-secreting beta-cells under in vitro conditions of glucolipotoxicity.