Document Detail


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.
MedLine Citation:
PMID:  20460097     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Noaman M Hasan; Melissa J Longacre; Mohammed Seed Ahmed; Mindy A Kendrick; Harvest Gu; Claes-Goran Ostenson; Toshiyuki Fukao; Michael J MacDonald
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-09
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  499     ISSN:  1096-0384     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-14     Completed Date:  2010-06-22     Revised Date:  2012-03-29    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  62-8     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
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MeSH Terms
Descriptor/Qualifier:
ATP Citrate (pro-S)-Lyase / genetics,  metabolism*
Animals
Base Sequence
Cell Line
Coenzyme A-Transferases / antagonists & inhibitors*,  genetics,  metabolism*
Diabetes Mellitus, Type 2 / genetics,  physiopathology*
Disease Models, Animal
Gene Knockdown Techniques
Insulin / secretion*
Islets of Langerhans / enzymology*,  secretion*
Male
Mitochondria / enzymology
Models, Biological
RNA, Messenger / genetics,  metabolism
RNA, Small Interfering / genetics
Rats
Rats, Wistar
Grant Support
ID/Acronym/Agency:
DK28348/DK/NIDDK NIH HHS; R01 DK028348-26/DK/NIDDK NIH HHS; R01 DK028348-28/DK/NIDDK NIH HHS; R01 DK028348-29/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Insulin; 0/RNA, Messenger; 0/RNA, Small Interfering; EC 2.3.3.8/ATP Citrate (pro-S)-Lyase; EC 2.8.3.-/Coenzyme A-Transferases; EC 2.8.3.5/3-ketoacid CoA-transferase
Comments/Corrections

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