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This Article Full Text Full Text (PDF) All Versions of this Article: 292/3/E693    most recent 00423.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Carpentier, A. C. Articles by Baillargeon, J.-P. Search for Related Content PubMed PubMed Citation Articles by Carpentier, A. C. Articles by Baillargeon, J.-P.

Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans

¹Division of Endocrinology, Department of Medicine, and ²Department of Clinical Biochemistry, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Québec, Canada

Submitted 17 August 2006 ; accepted in final form 23 October 2006

Insulin increases plasma nonesterified fatty acid (NEFA) clearance in humans, but whether this is independent of change in plasma NEFA appearance is currently unknown. Nine nondiabetic men (age: 28 ± 3 yr, body mass index: 27.2 ± 1.7 kg/m²) underwent euglycemic clamps to maintain low (LINS) vs. high (HINS) physiological insulin levels for 6 h. An intravenous infusion of heparin + Intralipid (HI) was performed during 4 of the 6 h of the clamps (in the last 4 h at LINS and in the first 4 h at HINS), whereas saline infusion (SAL) was administered in the remaining 2 h to modulate plasma NEFA levels independently of plasma insulin levels. Four experimental conditions were obtained in each individual: LINS with saline (LINS/SAL) and with HI infusion (LINS/HI) and HINS with saline (HINS/SAL) and with HI infusion (HINS/HI). Plasma palmitate appearance during HINS/SAL was lower than during the three other experimental conditions (P < 0.05). In contrast, plasma linoleate appearance, as expected, was increased by HI independently of insulin level (P < 0.02). Plasma palmitate clearance during HINS/SAL was higher than LINS/SAL and LINS/HI (P < 0.008), and this increase was blunted during HINS/HI. We observed a linear decrease in plasma palmitate clearance with increasing plasma NEFA appearance independent of insulin levels. Plasma NEFA levels increased exponentially with increase in plasma NEFA appearance. We conclude that insulin stimulates plasma NEFA clearance by reducing the endogenous appearance rate of NEFA. The relationship between plasma NEFA level and appearance rate is nonlinear.

human; insulin action; lipid metabolism; fatty acid metabolism