Summary
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.
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Abbreviations
- NEFA:
-
Non-esterified fatty acids
- ivGTT:
-
intravenous glucose tolerance test
- AIR:
-
acute insulin response
- NIDDM:
-
non-insulin-dependent diabetes mellitus
References
Yamaguchi K, Takoshima S, Masuyama T, Matsuoka A (1978) Effects of electric stress on insulin secretion and glucose metabolism in rats fed with a high fat diet. Endocrinol Jpn 29: 415–419
Crespin SR, Greenough WB, Steinberg D (1973) Stimulation of insulin secretion by long-chain free fatty acids. J Clin Invest 53: 1979–1984
Sako Y, Grill V (1990) A 48-h lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and Β-cell oxidation through a process likely coupled to fatty acid oxidation. Endocrinology 127: 1580–1589
Zhou YP, Grill V (1994) Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 93: 870–876
Paolisso G, Tataranni PA, Bogardus C, Howard BV, Ravussin E (1994) High concentration of FFA is a risk factor for the development of NIDDM. Diabetes 43 [Suppl 1] 75A (Abstract)
Diabetes mellitus (1985) Report of a WHO study group. World Health Organization 727, pp 9–17
Ferrannini E (1990) The theoretical basis of indirect calorimetry: methodological and interpretative problems. Metabolism 258: 339–402
Segal KR, Van Loan M, Fitzgerald PI, Hodgdon JA, Van Itallie TB (1988) Lean body mass estimation by bioelectrical impedance analysis: a four site cross-validation study. Am J Clin Nutr 47: 7–13
Paolisso G, Di Maro G, Pizza G, D'Amore A, Sgambato S, Tesauro P, Varricchio M, D'Onofrio F (1992) Plasma GSH/GSSG affects glucose homeostasis in healthy subjects and non-insulin dependent diabetics. Am J Physiol 263: E435-E440
Dole VP, Meinertz H (1960) Microdetermination of long-chain fatty acids in plasma and tissues. J Biol Chem 235: 2595–2599
Polonsky KS, Rubenstein AH (1986) Current approach to measurements of insulin secretion. Diabetes Metab Rev 2: 315–330
Tillil H, Shapiro ET, Miller MA et al. (1988) Dose dependent effect of oral and intravenous glucose on insulin secretion and clearance in normal man. Am J Physiol 17: E349-E357
Randle PL, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty acid cycle, its role in insulin sensitivity and the metabolic disturbances in diabetes mellitus. Lancet I. 785–789
Randle PJ, Priestman DA, Mistry S, Halsall A (1994) Mechanisms modifying glucose oxidation in diabetes mellitus. Diabetologia 37 [Suppl 2]: S155-S161
Berne C (1975) The oxidation of fatty acids and ketone bodies in mouse pancreatic islets. Biochem J 152: 661–665
Goberna R, Tamarit J, Osoris J, Fussgauger R, Tamarit J, Pfeiffer EF (1974) Action of B-hydroxybutirate, acetoacetate and palmitate on the insulin release from the perfused isolated rat pancreas. Horm Metab Res 6: 256–259
Malaisse WJ, Malaisse-Lagae F (1968) Stimulation of insulin secretion by non-carbohydrate metabolism. J Lab Clin Med 72: 438–448
Malaisse WJ, Lemonnier D, Malaisse-Lagae F, Monde-Ibaum IM (1969) Secretion of and sensitivity to insulin in obese rats fed a high fat diet. Horm Metab Res 1: 9–12
Borg LAH (1981) Effect of octanoate and ketone bodies on the structure and function of isolated pancreatic islets in tissue culture. Acta Endocrinol 96: 505–509
Capito K, Hansen SE, Hedeskov CJ, Thomas PJ (1992) Fat induced changes in mouse pancreatic islets, insulin secretion, insulin biosynthesis and glucose metabolism. Acta Diabetol 28: 193–198
Opara EC, Garfinkel M, Hubbard VS, Burch WM, Akwari OE (1994) Effect of fatty acids on insulin release: role of chain length and degree of unsaturation. Am J Physiol 266: E635-E639
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Paolisso, G., Gambardella, A., Amato, L. et al. Opposite effects of short- and long-term fatty acid infusion on insulin secretion in healthy subjects. Diabetologia 38, 1295–1299 (1995). https://doi.org/10.1007/BF00401761
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DOI: https://doi.org/10.1007/BF00401761