| Lipid-induced insulin resistance is associated with increased monocyte expression of scavenger receptor CD36 and internalization of oxidized LDL. | |
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MedLine Citation:
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PMID: 19521352 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Elevated free fatty acids (FFAs) contribute to the development of insulin resistance, type 2 diabetes mellitus (T2DM), and may be atherogenic. We tested the relationship among lipid-induced insulin resistance, endothelial dysfunction, and monocyte capacity to form foam cells through scavenger receptor A (SRA) and CD36. Ten healthy subjects underwent 24-h infusion of Intralipid/heparin and saline (0.5 ml/min) on two separate occasions followed by brachial artery reactivity testing and a euglycemic hyperinsulinemic (80 mU/(kg.min)) clamp study to determine insulin sensitivity. Isolation of blood monocytes was performed 24 h after infusion. Surface expression and function of CD36 and SRA to take up oxidized low-density lipoprotein (oxLDL) was determined by flow cytometry and quantitative confocal imaging. Lipid infusion resulted in a twofold increase in serum FFA levels, reduced whole-body glucose disposal by approximately 20% (P < 0.05), and possibly impaired endothelial-dependent vasodilation (P = 0.1). Blood monocytes obtained during lipid infusion demonstrated a approximately 25% increase in cell surface expression of CD36 (P < 0.05) but no change in SRA expression. Enhanced CD36 expression was associated with a 50% increase in internalization of oxLDL (P < 0.05). The increase in CD36 surface expression during lipid infusion correlated inversely with glucose disposal (P < 0.05) and not with FFA levels or brachial artery dilation. These data support a role for FFAs in induction of insulin resistance and provide a link to atherogenic mechanisms mediated by expression of scavenger receptor CD36. |
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Authors:
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Sangeeta R Kashyap; Adriana G Ioachimescu; Heather L Gornik; Thottathil Gopan; Michael B Davidson; Antonie Makdissi; Jennifer Major; Maria Febbraio; Roy L Silverstein |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-06-11 |
Journal Detail:
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Title: Obesity (Silver Spring, Md.) Volume: 17 ISSN: 1930-7381 ISO Abbreviation: Obesity (Silver Spring) Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-20 Completed Date: 2010-05-13 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 101264860 Medline TA: Obesity (Silver Spring) Country: United States |
Other Details:
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Languages: eng Pagination: 2142-8 Citation Subset: IM |
Affiliation:
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Department of Endocrinology, Diabetes and Metabolism, Endocrinology Institute, Lerner Research Institute; Cleveland Clinic Foundation, Cleveland, Ohio, USA. kashyas@ccf.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Anticoagulants / administration & dosage, pharmacology Antigens, CD36 / blood* Brachial Artery / drug effects Endothelium Fat Emulsions, Intravenous / administration & dosage, pharmacology* Fatty Acids, Nonesterified / blood* Female Flow Cytometry Foam Cells / metabolism Glucose / metabolism Heparin / administration & dosage, pharmacology Humans Insulin Resistance / immunology, physiology* Lipoproteins, LDL / metabolism* Male Microscopy, Confocal Middle Aged Monocytes / metabolism* Reference Values Scavenger Receptors, Class A / metabolism* Vasodilation / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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1UL1RR024989/RR/NCRR NIH HHS; 5K12RR023264/RR/NCRR NIH HHS; HL087018/HL/NHLBI NIH HHS; M01 RR018390-056204/RR/NCRR NIH HHS; P01 HL087018-01A1/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anticoagulants; 0/Antigens, CD36; 0/Fat Emulsions, Intravenous; 0/Fatty Acids, Nonesterified; 0/Lipoproteins, LDL; 0/Scavenger Receptors, Class A; 0/oxidized low density lipoprotein; 50-99-7/Glucose; 9005-49-6/Heparin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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