Abstract
Insulin resistance in adipose tissue increases the release of free fatty acids into the circulation, which likely contributes to impaired insulin action in liver and skeletal muscle associated with obesity. However, reliable assessment of adipose tissue insulin resistance requires performing a hyperinsulinemic-euglycemic clamp procedure in conjunction with a fatty acid tracer infusion to determine insulin-mediated suppression of lipolytic rate. We developed a simpler method for evaluating adipose tissue insulin resistance in vivo, determined as the product of palmitate rate of appearance into the bloodstream and plasma insulin concentration during basal conditions. We validated our Adipose Tissue Insulin Resistance Index (ATIRI) by comparison with an assessment of adipose tissue insulin resistance determined by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with a palmitate tracer infusion in 47 obese nondiabetic subjects (body mass index: 40.1 ± 9.3 kg/m(2)). We found the ATIRI correlated closely with adipose tissue insulin resistance assessed during the clamp procedure (r =-0.854, P < 0.001). These results demonstrate that the ATIRI provides a reliable index of adipose tissue insulin resistance in obese subjects.
Highlights
Insulin resistance in adipose tissue increases the release of free fatty acids into the circulation, which likely contributes to impaired insulin action in liver and skeletal muscle associated with obesity
Insulin infusion resulted in a 7-fold range in percent suppression of palmitate rate of appearance (Ra) and there was more than a 10-fold range in Adipose Tissue Insulin Resistance Index (ATIRI) values (Table 2), which enhanced our ability to evaluate the relationship between the ATIRI and adipose tissue insulin resistance derived from the clamp procedure
Impaired insulin-mediated suppression of adipose tissue triglyceride lipolysis and excessive release of free fatty acids (FFAs) into plasma are likely involved in the pathogenesis of hepatic and skeletal muscle insulin resistance in obese people [1, 14, 15]
Summary
Insulin resistance in adipose tissue increases the release of free fatty acids into the circulation, which likely contributes to impaired insulin action in liver and skeletal muscle associated with obesity. Reliable assessment of adipose tissue insulin resistance requires performing a hyperinsulinemic-euglycemic clamp procedure in conjunction with a fatty acid tracer infusion to determine insulin-mediated suppression of lipolytic rate. We validated our Adipose Tissue Insulin Resistance Index (ATIRI) by comparison with an assessment of adipose tissue insulin resistance determined by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with a palmitate tracer infusion in 47 obese nondiabetic subjects (body mass index: 40.1 ± 9.3 kg/m2). Reliable assessment of adipose tissue insulin resistance requires performing a hyperinsulinemic-euglycemic clamp procedure in conjunction with a fatty acid tracer infusion to determine insulin-mediated suppression of adipose tissue lipolysis [2]. We tested and validated a simple tracer infusion method to determine the Adipose Tissue Insulin Resistance Index (ATIRI), based on the principle of an index used to assess insulin sensitivity in the liver that is derived from basal glucose kinetics and plasma insulin concentration [4]
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