Document Detail

Relationship between adipose tissue lipolytic activity and skeletal muscle insulin resistance in nondiabetic women.
MedLine Citation:
PMID:  22492868     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Increased adipose tissue lipolytic activity is considered an important factor in the pathogenesis of skeletal muscle insulin resistance associated with obesity.
OBJECTIVE: The objective of the study was to evaluate the relationship between the rate of release of free fatty acids (FFA) into plasma and skeletal muscle insulin sensitivity in human subjects.
METHODS: We determined the palmitate rate of appearance (Ra) per kilogram fat-free mass (an index of FFA availability to lean tissues) during basal conditions and during insulin infusion (to simulate postprandial insulin concentrations) and skeletal muscle insulin sensitivity, defined as the percent increase in the glucose rate of disappearance, in 110 nondiabetic women (body mass index 20.6-46.4 kg/m(2)) by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer methods.
RESULTS: Basal (r(s) = -0.379, P < 0.001) and insulin-suppressed (r(s) = -0.631, P < 0.001) palmitate Ra correlated negatively with skeletal muscle insulin sensitivity. However, the strength of the correlation was greater for palmitate Ra during insulin infusion than palmitate Ra during basal conditions (P = 0.0007) when lipolytic rates and FFA availability were reduced to less than 20% of basal values. The relative suppression of palmitate Ra correlated directly with the relative stimulation of glucose rate of disappearance during insulin infusion (r(s) = 0.530, P < 0.001).
CONCLUSION: These data suggest that the correlation between FFA kinetics and muscle glucose metabolism is due to multiorgan insulin resistance rather than a direct effect of FFA itself on skeletal muscle insulin action and challenge the view that increased adipose tissue lipolytic rate is an important cause of insulin resistance.
Faidon Magkos; Elisa Fabbrini; Caterina Conte; Bruce W Patterson; Samuel Klein
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-06
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  97     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-09     Completed Date:  2012-09-26     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1219-23     Citation Subset:  AIM; IM    
Center for Human Nutrition, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8031, St. Louis, Missouri 63110, USA.
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MeSH Terms
Adipose Tissue / drug effects,  metabolism*
Diabetes Mellitus / metabolism
Fatty Acids, Nonesterified / administration & dosage,  pharmacokinetics,  pharmacology
Glucose Clamp Technique
Insulin / administration & dosage,  pharmacology
Insulin Resistance / physiology*
Lipolysis / drug effects,  physiology*
Middle Aged
Muscle, Skeletal / drug effects,  metabolism*
Obesity / complications,  metabolism*
Palmitic Acid / administration & dosage,  pharmacokinetics
Radioactive Tracers
Young Adult
Grant Support
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Insulin; 0/Radioactive Tracers; 57-10-3/Palmitic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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