Details

Autor(en) / Beteiligte

• Yoshii, Hidenori
• Lam, Tony K. T
• Gupta, Neehar
• Goh, Tracy
• Haber, C. Andrew
• Uchino, Hiroshi
• Kim, Tony T. Y
• Chong, Victor Z
• Shah, Keyur
• Fantus, I. George
• Mari, Andrea
• Kawamori, Ryuzo
• Giacca, Adria

Titel

Effects of portal free fatty acid elevation on insulin clearance and hepatic glucose flux

Ist Teil von

• American journal of physiology: endocrinology and metabolism, 2006-06, Vol.290 (6), p.E1089-E1097

Ort / Verlag

United States

Erscheinungsjahr

2006

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Departments of 1 Physiology and 3 Medicine, University of Toronto, Toronto, Ontario, Canada; 2 Department of Medicine, Juntendo University, Tokyo, Japan; and 4 Institute of Systems Science and Biomedical Engineering, National Research Council, Padua, Italy Submitted 5 July 2005 ; accepted in final form 29 December 2005 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 µeq·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. insulin resistance; hepatic glucose production; visceral obesity Address for reprint requests and other correspondence: A. Giacca, Dept. of Physiology, Univ. of Toronto, Medical Sciences Bldg., Rm. 3336, Toronto, ON M5S1A8 Canada (e-mail: adria.giacca{at}utoronto.ca )