title: Acute elevation of free fatty acids impairs hepatic glucose uptake in conscious rats.
abstract: To investigate the dose-dependent effect of free fatty acid (FFA) on the hepatic glucose uptake (HGU), we determined hepatic glucose fluxes by a dual tracer technique during the basal state and euglycemic hyperinsulinemic clamp combined with a portal glucose load in three groups of rats given saline (saline), low-dose lipid (lipid-L), or high-dose lipid infusion (lipid-H). In the basal state, lipid infusion dose-dependently increased plasma FFA (saline, 400 +/- 50; lipid-L, 550 +/- 30; lipid-H, 1700 +/- 270 micromol l(-1); mean +/- S.E). Endogenous glucose production (EGP) in lipid-H was 63.5 +/- 5.5 micromol kg(-1) min(-1) and significantly higher than in the saline and lipid-L (40.2 +/- 2.9, 47.6 +/- 3.1 micromol kg(-1) min(-1), respectively). During euglycemic hyperinsulinemic clamp, plasma FFA decreased to 130 +/- 30 micromol l(-1) in saline, but remained at basal levels in lipid-L and lipid-H (470 +/- 30 and 1110 +/- 180 micromol l(-1), respectively). Insulin-suppressed EGP was complete in saline and lipid-L, but impaired in lipid-H (38.0 +/- 6.4 micromol kg(-1) min(-1)). Elevated FFA dose-dependently reduced HGU (saline, 12.2 +/- 0.9; lipid-L, 8.6 +/- 0.6; lipid-H, 4.7 +/- 1.4 micromol kg(-1) min(-1)). In conclusion, acutely elevated FFA impairs HGU as well as insulin-mediated suppression of EGP during hyperinsulinemic clamp with portal glucose loading. Impaired hepatic glucose uptake associated with elevated FFA may contribute to the development of insulin resistance in obesity and type 2 diabetes.
authors.affiliation: Department of Internal Medicine and Therapeutics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka Prefecture 565-0871, Japan.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Nakahara
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shiba
authors.forename: Akio
authors.initials: A
authors.lastname: Kuroda
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hatazaki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kajimoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Kubota
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005947:Glucose / Q000008:administration & dosage / Q000096:biosynthesis / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D007601:Jugular Veins; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose