Document Detail


Diverse roles for protein kinase C delta and protein kinase C epsilon in the generation of high-fat-diet-induced glucose intolerance in mice: regulation of lipogenesis by protein kinase C delta.
MedLine Citation:
PMID:  19809797     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS/HYPOTHESIS: This study aimed to determine whether protein kinase C (PKC) delta plays a role in the glucose intolerance caused by a high-fat diet, and whether it could compensate for loss of PKCepsilon in the generation of insulin resistance in skeletal muscle. METHODS: Prkcd (-/-), Prkce (-/-) and wild-type mice were fed high-fat diets and subjected to glucose tolerance tests. Blood glucose levels and insulin responses were determined during the tests. Insulin signalling in liver and muscle was assessed after acute in vivo insulin stimulation by immunoblotting with phospho-specific antibodies. Activation of PKC isoforms in muscle from Prkce (-/-) mice was assessed by determining intracellular distribution. Tissues and plasma were assayed for triacylglycerol accumulation, and hepatic production of lipogenic enzymes was determined by immunoblotting. RESULTS: Both Prkcd (-/-) and Prkce (-/-) mice were protected against high-fat-diet-induced glucose intolerance. In Prkce (-/-) mice this was mediated through enhanced insulin availability, while in Prkcd (-/-) mice the reversal occurred in the absence of elevated insulin. Neither the high-fat diet nor Prkcd deletion affected maximal insulin signalling. The activation of PKCdelta in muscle from fat-fed mice was enhanced by Prkce deletion. PKCdelta-deficient mice exhibited reduced liver triacylglycerol accumulation and diminished production of lipogenic enzymes. CONCLUSIONS/INTERPRETATION: Deletion of genes encoding isoforms of PKC can improve glucose intolerance, either by enhancing insulin availability in the case of Prkce, or by reducing lipid accumulation in the case of Prkcd. The absence of PKCepsilon in muscle may be compensated by increased activation of PKCdelta in fat-fed mice, suggesting that an additional role for PKCepsilon in this tissue is masked.
Authors:
G Frangioudakis; J G Burchfield; S Narasimhan; G J Cooney; M Leitges; T J Biden; C Schmitz-Peiffer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-07
Journal Detail:
Title:  Diabetologia     Volume:  52     ISSN:  1432-0428     ISO Abbreviation:  Diabetologia     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2010-01-21     Completed Date:  2010-04-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2616-20     Citation Subset:  IM    
Affiliation:
Diabetes and Obesity Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales, 2010, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose / metabolism
Crosses, Genetic
Dietary Fats / adverse effects*
Gene Deletion
Glucose Intolerance / blood,  chemically induced*,  enzymology
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
Muscle, Skeletal / enzymology
Protein Kinase C-delta / deficiency*,  genetics,  metabolism*
Protein Kinase C-epsilon / deficiency*,  genetics,  metabolism*
Triglycerides / metabolism
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Dietary Fats; 0/Triglycerides; EC 2.7.11.13/Protein Kinase C-delta; EC 2.7.11.13/Protein Kinase C-epsilon

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