| Abnormal in vivo myocardial energy substrate uptake in diet-induced type 2 diabetic cardiomyopathy in rats. | |
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MedLine Citation:
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PMID: 20159856 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The purpose of this study was to determine in vivo myocardial energy metabolism and function in a nutritional model of type 2 diabetes. Wistar rats rendered insulin-resistant and mildly hyperglycemic, hyperinsulinemic, and hypertriglyceridemic with a high-fructose/high-fat diet over a 6-wk period with injection of a small dose of streptozotocin (HFHFS) and control rats were studied using micro-PET (microPET) without or with a euglycemic hyperinsulinemic clamp. During glucose clamp, myocardial metabolic rate of glucose measured with [(18)F]fluorodeoxyglucose ([(18)F]FDG) was reduced by approximately 81% (P < 0.05), whereas myocardial plasma nonesterified fatty acid (NEFA) uptake as determined by [(18)F]fluorothia-6-heptadecanoic acid ([(18)F]FTHA) was not significantly changed in HFHFS vs. control rats. Myocardial oxidative metabolism as assessed by [(11)C]acetate and myocardial perfusion index as assessed by [(13)N]ammonia were similar in both groups, whereas left ventricular ejection fraction as assessed by microPET was reduced by 26% in HFHFS rats (P < 0.05). Without glucose clamp, NEFA uptake was approximately 40% lower in HFHFS rats (P < 0.05). However, myocardial uptake of [(18)F]FTHA administered by gastric gavage was significantly higher in HFHFS rats (P < 0.05). These abnormalities were associated with reduced Glut4 mRNA expression and increased Cd36 mRNA expression and mitochondrial carnitine palmitoyltransferase 1 activity (P < 0.05). HFHFS rats display type 2 diabetes complicated by left ventricular contractile dysfunction with profound reduction in myocardial glucose utilization, activation of fatty acid metabolic pathways, and preserved myocardial oxidative metabolism, suggesting reduced myocardial metabolic efficiency. In this model, increased myocardial fatty acid exposure likely occurs from circulating triglyceride, but not from circulating plasma NEFA. |
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Authors:
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S?bastien L M?nard; Etienne Croteau; Otman Sarrhini; Roselle G?linas; Pascal Brassard; Ren? Ouellet; M'hamed Bentourkia; Johannes E van Lier; Christine Des Rosiers; Roger Lecomte; Andr? C Carpentier |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-16 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 298 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-14 Completed Date: 2010-05-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E1049-57 Citation Subset: IM |
Affiliation:
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Division of Endocrinology, Department of Medicine, University de Sherbrooke, Sherbrooke, QC, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Cardiomyopathies / etiology, metabolism*, radionuclide imaging Diabetes Mellitus, Experimental / complications, metabolism*, radionuclide imaging Energy Metabolism / physiology* Enzyme-Linked Immunosorbent Assay Fatty Acids, Nonesterified / blood Glucose / metabolism* Glucose Clamp Technique Heart / radionuclide imaging Heart Failure / etiology, metabolism, radionuclide imaging Insulin / blood Male Myocardium / metabolism* Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Triglycerides / blood |
| Grant Support | |
ID/Acronym/Agency:
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MOP-53094//Canadian Institutes of Health Research; PRG-80137//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Nonesterified; 0/Triglycerides; 11061-68-0/Insulin; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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