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Lower succinyl-CoA:3-ketoacid-CoA transferase (SCOT) and ATP citrate lyase in pancreatic islets of a rat model of type 2 diabetes: knockdown of SCOT inhibits insulin release in rat insulinoma cells.

Authors: Hasan, NM  Longacre, MJ  Seed Ahmed, M  Kendrick, MA  Gu, H  Ostenson, CG  Fukao, T  MacDonald, MJ 
Citation: Hasan NM, etal., Arch Biochem Biophys. 2010 Jul;499(1-2):62-8. Epub 2010 May 9.
Pubmed: (View Article at PubMed) PMID:20460097
DOI: Full-text: DOI:10.1016/j.abb.2010.05.007

Succinyl-CoA:3-ketoacid-CoA transferase (SCOT) is a mitochondrial enzyme that catalyzes the reversible transfer of coenzyme-A from acetoacetyl-CoA to succinate to form acetoacetate and succinyl-CoA. mRNAs of SCOT and ATP citrate lyase were decreased 55% and 58% and enzyme activities were decreased >70% in pancreatic islets of the GK rat, a model of type 2 diabetes. INS-1 832/13 cells were transfected with shRNAs targeting SCOT mRNA to generate cell lines with reduced SCOT activity. Two cell lines with >70% knockdown of SCOT activity showed >70% reduction in glucose- or methyl succinate-plus-beta-hydroxybutyrate-stimulated insulin release. Less inhibition of insulin release was observed with two cell lines with less knockdown of SCOT. Previous studies showed knockdown of ATP citrate lyase in INS-1 832/13 cells does not lower insulin release. The results further support work that suggests mitochondrial pathways involving SCOT which supply acetoacetate for export to the cytosol are important for insulin secretion.

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CRRD Object Information
CRRD ID: 2326185
Created: 2010-06-29
Species: All species
Last Modified: 2010-06-29
Status: ACTIVE



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