Acute elevation of free fatty acids impairs hepatic glucose uptake in conscious rats.
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.
Nakahara
Itsuro
I
Department of Internal Medicine and Therapeutics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka Prefecture 565-0871, Japan.
Matsuhisa
Munehide
M
Shiba
Yuichi
Y
Kuroda
Akio
A
Nakatani
Yoshihisa
Y
Hatazaki
Masahiro
M
Kajimoto
Yoshitaka
Y
Kubota
Minoru
M
Yamasaki
Yoshimitsu
Y
Hori
Masatsugu
M
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
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose