title: Effects of portal free fatty acid elevation on insulin clearance and hepatic glucose flux.
abstract: We tested the hypothesis that, due to greater hepatic free fatty acid (FFA) load, portal delivery of FFAs, as in visceral obesity, induces hyperinsulinemia and increases endogenous glucose production to a greater extent than peripheral FFA delivery. For 5 h, 10 microeq.kg(-1).min(-1) portal oleate (n = 6), equidose peripheral oleate (n = 5), or saline (n = 6) were given intravenously to conscious dogs infused with a combination of portal and peripheral insulin to enable calculation of hepatic insulin clearance during a pancreatic euglycemic clamp. Peripheral FFAs were similar with both oleate treatments and were threefold greater than in controls. Portal FFAs were 1.5- to 2-fold greater with portal than with peripheral oleate. Peripheral insulin concentrations were greatest with portal oleate, intermediate with peripheral oleate (P < 0.001 vs. portal oleate or controls), and lowest in controls, consistent with corresponding reductions in plasma insulin clearance and hepatic insulin clearance. Although endogenous glucose production did not differ between the two routes of oleate delivery, total glucose output (endogenous glucose production plus glucose cycling) was greater with portal than with peripheral oleate (P < 0.001) despite the higher insulin levels. In conclusion, during euglycemic clamps in dogs, the main effect of short-term elevation in portal FFA is to generate peripheral hyperinsulinemia. This may, in the long term, contribute to the metabolic and cardiovascular risk of visceral obesity.
authors.affiliation: Dept. of Physiology, Univ. of Toronto, Medical Sciences Bldg., Rm. 3336, Toronto, ON M5S1A8 Canada.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yoshii
authors.forename: Tony K T
authors.initials: TK
authors.lastname: Lam
authors.forename: Neehar
authors.initials: N
authors.lastname: Gupta
authors.forename: Tracy
authors.initials: T
authors.lastname: Goh
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Haber
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchino
authors.forename: Tony T Y
authors.initials: TT
authors.lastname: Kim
authors.forename: Victor Z
authors.initials: VZ
authors.lastname: Chong
authors.forename: Keyur
authors.initials: K
authors.lastname: Shah
authors.forename: I George
authors.initials: IG
authors.lastname: Fantus
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006728:Hormones / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D011168:Portal System / Q000378:metabolism; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D019301:Oleic Acid; D005947:Glucose