Opposite effects of short- and long-term fatty acid infusion on insulin secretion in healthy subjects.
Our study investigates short- and long-term effects of infusion of non-esterified fatty acids (NEFA) on insulin secretion in healthy subjects. Twelve healthy individuals underwent a 24-h Intralipid (10% triglyceride emulsion) infusion at a rate of 0.4 ml/min with a simultaneous infusion of heparin (a bolus of 200 U followed by 0.2 U/min per kg body weight). After an overnight fast (baseline), at 6 and at 24 h of Intralipid infusion and 24 h after Intralipid discontinuation (recovery test), all subjects underwent an intravenous glucose tolerance test (iv-GTT) (25 g of glucose/min). Intralipid infusion caused a threefold rise in plasma NEFA concentrations with no difference between the 6- and the 24-h concentrations. Compared to baseline acute insulin response (AIR) (AIR = 63 +/- 8 mU/l), short-term (6-h) Intralipid infusion was associated with a significant increase in AIR (86 +/- 12 mU/l p < 0.01); in contrast, long-term (24-h) Intralipid delivery was associated with inhibition of AIR (31 +/- 5 mU/l) compared to baseline (p < 0.001) and to the 6-h (p < 0.03) triglyceride emulsion infusion. Intralipid infusion was associated with a progressive and significant decline in respiratory quotient (RQ). A positive correlation between changes in fasting plasma NEFA concentrations and AIR at the 6-h infusion (r = 0.89 p < 0.001) was found. In contrast, at the end of the Intralipid infusion period, changes in plasma NEFA concentrations and AIR were negatively correlated (r = -0.87 p < 0.001). The recovery test showed that fasting plasma NEFA concentrations, RQ and AIR had returned to baseline values. In the control study (n = 8) 0.9% NaCl infusion did not mimick the effect of Intralipid. In conclusion, our study demonstrates that short- and long-term exposures of beta cells to high plasma NEFA concentrations have opposite effects on glucose-induced insulin secretion.
Paolisso
G
G
Department of Geriatric Medicine and Metabolic Diseases, II University of Naples, Italy.
Gambardella
A
A
Amato
L
L
Tortoriello
R
R
D'Amore
A
A
Varricchio
M
M
D'Onofrio
F
F
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005215:Fasting; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000008:administration & dosage / Q000494:pharmacology
D001786:Blood Glucose; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides