| 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. | |
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MedLine Citation:
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PMID: 20460097 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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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:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-09 |
Journal Detail:
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Title: Archives of biochemistry and biophysics Volume: 499 ISSN: 1096-0384 ISO Abbreviation: Arch. Biochem. Biophys. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-14 Completed Date: 2010-06-22 Revised Date: 2012-03-29 |
Medline Journal Info:
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Nlm Unique ID: 0372430 Medline TA: Arch Biochem Biophys Country: United States |
Other Details:
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Languages: eng Pagination: 62-8 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP Citrate (pro-S)-Lyase
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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:
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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:
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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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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