Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans.
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.
Carpentier
André C
AC
Division of Endocrinology, Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4. andre.carpentier@usherbrooke.ca
Frisch
Frédérique
F
Brassard
Pascal
P
Lavoie
François
F
Bourbonnais
Annie
A
Cyr
Denis
D
Giguère
Robert
R
Baillargeon
Jean-Patrice
JP
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D019787:Linoleic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D019301:Oleic Acid / Q000097:blood; D019308:Palmitic Acid / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D019301:Oleic Acid; D019308:Palmitic Acid; D005934:Glucagon; D019787:Linoleic Acid; D005990:Glycerol