The effect of insulin on the intracellular distribution of 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid in rats

Abstract

Purpose: The aim of this study was to determine the effect of hyperinsulinemia on myocardial and hepatic distribution and metabolism of 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA).

Procedures: Mitochondrial retention and intracellular lipid incorporation of [18F]FTHA were compared to that of [14C]-2-bromopalmitate or [14C]palmitate during hyperinsulinemic clamp vs. saline infusion in male Wistar rats.

Results: Mitochondrial 18F activity was increased in the heart (1.7 +/- 0.4 vs. 0.5 +/- 0.1% ID/g, P < 0.05), whereas it was reduced in the liver (1.1 +/- 0.3 vs. 1.8 +/- 0.4% ID/g, P < 0.05) during insulin vs. saline infusion, respectively. Mitochondrial [14C]-2-bromopalmitate activity was affected by insulin in a similar way in both tissues. The fractional esterification of [18F]FTHA into triglycerides was impaired compared to [14C]palmitate in both tissues, and [18F]FTHA was insensitive to the shift of esterification of fatty acids into complex lipids in response to insulin.

Conclusions: [18F]FTHA is sensitive to insulin-induced modifications of free fatty acid oxidative metabolism in rats but is insensitive to changes in nonoxidative fatty acid metabolism.