Relationship between adipose tissue lipolytic activity and skeletal muscle insulin resistance in nondiabetic women
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Relationship between adipose tissue lipolytic activity and skeletal muscle insulin resistance in nondiabetic women. / Magkos, Faidon; Fabbrini, Elisa; Conte, Caterina; Patterson, Bruce W; Klein, Samuel.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 7, 2012, p. E1219-E1223.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Relationship between adipose tissue lipolytic activity and skeletal muscle insulin resistance in nondiabetic women
AU - Magkos, Faidon
AU - Fabbrini, Elisa
AU - Conte, Caterina
AU - Patterson, Bruce W
AU - Klein, Samuel
N1 - (Ekstern)
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Adipose Tissue/drug effects
KW - Adult
KW - Aged
KW - Diabetes Mellitus/metabolism
KW - Fatty Acids, Nonesterified/administration & dosage
KW - Female
KW - Glucose Clamp Technique
KW - Humans
KW - Insulin/administration & dosage
KW - Insulin Resistance/physiology
KW - Lipolysis/drug effects
KW - Middle Aged
KW - Muscle, Skeletal/drug effects
KW - Obesity/complications
KW - Palmitic Acid/administration & dosage
KW - Radioactive Tracers
KW - Young Adult
U2 - 10.1210/jc.2012-1035
DO - 10.1210/jc.2012-1035
M3 - Journal article
C2 - 22492868
VL - 97
SP - E1219-E1223
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 7
ER -
ID: 290033959