Document Detail


Infusing lipid raises plasma free fatty acids and induces insulin resistance in muscle microvasculature.
MedLine Citation:
PMID:  19567533     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Insulin recruits muscle microvasculature, which increases the endothelial exchange surface area to facilitate substrate delivery. Elevated plasma concentrations of free fatty acids (FFAs) cause insulin resistance. OBJECTIVES: The aim of the study was to examine whether FFAs cause insulin resistance in human muscle microvasculature. SETTING: The study was conducted at the General Clinical Research Center at the University of Virginia. METHODS: Twenty-two healthy subjects were studied under two protocols designed to raise plasma insulin concentrations to postprandial levels using either an insulin infusion or a mixed meal challenge. Within each protocol, subjects were studied twice. In random order, they received a 5-h systemic infusion of either saline or Intralipid/heparin. Three hours into the infusion, baseline muscle microvascular blood volume (MBV), microvascular flow velocity, and microvascular blood flow (MBF) were measured. Each subject was then given either the mixed meal or a 1 mU/kg x min insulin clamp for 2 h. Microvascular parameters were again obtained 2 h after the meal or at the end of insulin infusion. RESULTS: Meal feeding and insulin infusion raised plasma insulin concentrations to approximately 200 pm, and each significantly increased muscle MBV (P = 0.03 and P < 0.01, respectively). MBF trended up after meal feeding (P = 0.08) and increased significantly after insulin infusion (P = 0.02). In the presence of Intralipid, neither the meal nor the insulin infusion increased muscle MBV and MBF. CONCLUSIONS: Compared to saline, lipid infusion raises plasma FFA concentrations and blocks the ability of insulin or meal to recruit muscle microvasculature. High plasma FFA concentrations may contribute to muscle insulin resistance and the microvascular complications of diabetes.
Authors:
Zhenqi Liu; Jia Liu; Linda A Jahn; Dale E Fowler; Eugene J Barrett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-06-30
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  94     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-07     Completed Date:  2009-09-23     Revised Date:  2010-09-02    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3543-9     Citation Subset:  AIM; IM    
Affiliation:
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, P.O. Box 801410, Charlottesville, Virginia 22908, USA. zl3e@virginia.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Volume
Fat Emulsions, Intravenous / administration & dosage*
Fatty Acids, Nonesterified / blood*
Female
Heparin / pharmacology
Humans
Insulin Resistance*
Male
Microcirculation
Muscle, Skeletal / blood supply*,  metabolism
Regional Blood Flow
Grant Support
ID/Acronym/Agency:
DK-073759/DK/NIDDK NIH HHS; DK-DK057878/DK/NIDDK NIH HHS; R01 DK073759-03/DK/NIDDK NIH HHS; RR-00847/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Fat Emulsions, Intravenous; 0/Fatty Acids, Nonesterified; 9005-49-6/Heparin

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