Trafficking of nonesterified fatty acids in insulin resistance and relationship to dysglycemia.

Abstract

In adipose, insulin functions to suppress intracellular lipolysis and secretion of nonesterified fatty acid (NEFA) into plasma. We applied glucose and NEFA minimal models (MM) following a frequently sampled intravenous glucose tolerance test (FSIVGTT) to assess glucose-specific and NEFA-specific insulin resistance. We used total NEFA and individual fatty acids in the NEFA MM, comparing the model parameters in metabolic syndrome (MetSyn) subjects (n = 52) with optimally healthy controls (OptHC; n = 14). Results are reported as mean difference (95% confidence interval). Using the glucose MM, MetSyn subjects had lower [-73% (-82, -57)] sensitivity to insulin (Si) and higher [138% (44, 293)] acute insulin response to glucose (AIRg). Using the NEFA MM, MetSyn subjects had lower [-24% (-35, -13)] percent suppression, higher [32% (15, 52)] threshold glucose (gs), and a higher [81% (12, 192)] affinity constant altering NEFA secretion (ϕ). Comparing fatty acids, percent suppression was lower in myristic acid (MA) than in all other fatty acids, and the stearic acid (SA) response was so unique that it did not fit the NEFA MM. MA and SA percent of total were increased at 50 min after glucose injection, whereas oleic acid (OA) and palmitic acid (PA) were decreased (P < 0.05). We conclude that the NEFA MM, as well as the response of individual NEFA fatty acids after a FSIVGTT, differ between OptHC and MetSyn subjects and that the NEFA MM parameters differ between individual fatty acids.