Prolonged Elevation of Plasma Free Fatty Acids Desensitizes the Insulin Secretory Response To Glucose In Vivo in Rats

摘要

Prolonged exposure of pancreatic islets to free fatty acids (FFAs) inhibits glucose-stimulated insulin secre- tion (GSIS) in vitro. However, FFA inhibition of GSIS has not been clearly demonstrated in vivo. We examined the in vivo effect of prolonged elevation of plasma FFAs on GSIS using a two-step hyperglycemic clamp in rats treated with a 48-h intravenous infusion of either 20/100 Intralipid plus heparin (INT) (5 μl/min plus heparin, 0.1 U/min; n=8), oleate (OLE) (1.3 μEq/min; n=6), Saline (SAL) n=6), or bovine serum albumin (BSA) (vehicle for OLE; n=5). Because there was no difference in any of the parameters between BSA and SAL rats, these groups were combined as control rats (CONT) (n =11). At the end of the 48-h OLE/INT/CONT infusions, after an overnight fast, plasma glucose was clamped for 2 h at 13 mmol/l and for another 2 h at 22 mmol/l. Preclamp plasma FFAs were elevated twofold (P< 0.01) Versus CONT with both INT and OLE (NS, INT vs. OLE).