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The ingestion of saturated fatty acid triacylglycerols acutely affects insulin secretion and insulin sensitivity in human subjects

Published online by Cambridge University Press:  09 March 2007

Melania Manco*
Affiliation:
Institute of Internal Medicine, Catholic University S. Cuore, School of Medicine, Largo A. Gemelli, 8, 00168, Rome, Italy
Alessandro Bertuzzi
Affiliation:
Institute of Systems Analysis and Informatics – CNR, Rome, Italy
Serenella Salinari
Affiliation:
Department of Systems Analysis and Informatics, University of Rome ‘La Sapienza’, Rome, Italy
Antonino Scarfone
Affiliation:
Institute of Internal Medicine, Catholic University S. Cuore, School of Medicine, Largo A. Gemelli, 8, 00168, Rome, Italy
Menotti Calvani
Affiliation:
Institute of Internal Medicine, Catholic University S. Cuore, School of Medicine, Largo A. Gemelli, 8, 00168, Rome, Italy
Aldo V. Greco
Affiliation:
Institute of Internal Medicine, Catholic University S. Cuore, School of Medicine, Largo A. Gemelli, 8, 00168, Rome, Italy
Geltrude Mingrone
Affiliation:
Institute of Internal Medicine, Catholic University S. Cuore, School of Medicine, Largo A. Gemelli, 8, 00168, Rome, Italy
*
*Corresponding author: Dr Melania Manco, fax +39 06 3054392, email melania.manco@rm.unicatt.it
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Abstract

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To assess the effects of acute dietary saturated fat intake on glucose-induced insulin secretion rate (ISR), measured by the C-peptide deconvolution method, and on insulin clearance and sensitivity, five obese and five normal-weight women (controls) were studied after either a 100g oral butter load or a 100ml water load. At 120min after the oral load a hyperglycaemic clamp was performed over 180min. A dramatic increase of ISR occurred after butter compared with the water challenge in the controls (1305·6 (SE 124·1) v. 616·1 (SE 52·5) pmol/min; P<0·01) and to a lesser degree in the obese subjects (1975·0 (SE 44·1) v. 1417·5 (SE 56·0) pmol/min; P<0·05). Insulin sensitivity was impaired after butter (0·60×10−2 (SE 0·11×10−2) v. 2·26×10−2 (SE 0·32×10−2) ml/min per kgFFM per (pmol/l); P<0·01) in the controls but not in the obese group. Insulin clearance during the clamp was reduced after butter compared with after the water load only in the controls (0·89 (SE 0·22) v. 1·70 (SE 0·15) litres/min; P<0·01). The data are consistent with the hypothesis that acute excess lipid availability may lead to a compensatory elevation in glucose-induced insulin secretion as a result of the decline in insulin sensitivity and a reduced insulin clearance.

Type
Review Article
Copyright
Copyright © The Nutrition Society 2004

References

Alstrup, KK, Gregersen, S, Jensen, HM, Thomsen, JL & Hermansen, K (1999) Differential effects of cis and trans fatty acids on insulin release from isolated mouse islets. Metabolism 48, 2229.Google ScholarPubMed
Boden, G, Ken, X, Rosner, J & Barton, M (1995) Effects of a 48-h fat infusion on insulin secretion and glucose utilization. Diabetes 44, 12391242.CrossRefGoogle ScholarPubMed
Borkman, M, Storlien, LH, Pan, DA, Jenkins, AB, Chisholm, DJ & Campbell, LV (1993) The relation between insulin sensitivity and the fatty-acid composition of skeletal muscle phospholipids. N Engl J Med 328, 238244.CrossRefGoogle ScholarPubMed
Brundin, T (1998) Whole body and splanchnic, metabolic, circulatory, and thermal effects of oral vs. intravenous fat administration. Am J Physiol 274, E684E691.Google ScholarPubMed
Carpentier, A, Mittelman, SD, Bergman, RN, Giacca, A & Lewis, GF (2000) Prolonged elevation of plasma free fatty acids impairs pancreatic beta-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes. Diabetes 49, 399408.CrossRefGoogle Scholar
Carpentier, A, Mittelman, SD, Lamarche, B, Bergman, RN, Giacca, A & Lewis, GF (1999) Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation. Am J Physiol 276, E1055E1066.Google ScholarPubMed
Crespin, SR, Greenough, WB & Steinberg, D (1973) Stimulation of insulin secretion by long-chain free fatty acids: a pancreatic effect. J Clin Invest 52, 19791984.CrossRefGoogle ScholarPubMed
DeFronzo, RA, Tobin, JD & Andres, R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237, E214E223.Google ScholarPubMed
Dobbins, RL, Chester, MW, Daniels, MB, McGarry, JD & Stein, DT (1998) Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans. Diabetes 47, 19131918.CrossRefGoogle ScholarPubMed
Dobbins, RL, Szczepaniak, LS, Myhill, J, Tamura, Y, Uchino, H, Giacca, A & McGarry, JD (2002) The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats. Diabetes 51, 18251833.CrossRefGoogle ScholarPubMed
Gasbarrini, G, Mingrone, G, Greco, AV & Castagneto, M (1996) An 18-year-old woman with familial chylomicronaemia who would not stick to a diet. Lancet 348, 794.CrossRefGoogle Scholar
Goodpaster, BH, Thaete, FL & Kelley, DE (2000) Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr 71, 885892.CrossRefGoogle ScholarPubMed
Greco, AV, Mingrone, G, Giancaterini, A, Manco, M, Morroni, M, Cinti, S, Granzotto, M, Vettor, R, Calastra, S & Ferrannini, E (2002) Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes 51, 144151.CrossRefGoogle ScholarPubMed
Heymsfield, SB, Lichtman, S, Baumgartner, RN, Wang, J, Kamen, Y, Aliprantis, A, Pierson, RN Jr (1990) Body composition of humans: comparison of two improved four-compartment models that differ in expense, technical complexity, and radiation exposure. Am J Clin Nutr 52, 5258.CrossRefGoogle ScholarPubMed
Joannic, JL, Auboiron, S, Raison, J, Basdevant, A, Bornet, F, Guy-Grand, B (1997) How the degree of unsaturation of dietary fatty acids influences the glucose and insulin responses to different carbohydrates in mixed meals. Am J Clin Nutr 65, 14271433.CrossRefGoogle ScholarPubMed
Koyama, K, Ken, G, Lee, Y & Unger, RH (1997) Tissue triglycerides, insulin resistance and insulin production. Implications for hyperinsulinemia of obesity. Am J Physiol 273, E708E713.Google ScholarPubMed
Lee, Y, Hirose, H, Ohneda, M, Johnson, JH, McGarry, JD & Unger, RH (1994) Beta-cell lipotoxicity in the pathogenesis of non insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte beta-cell relationship. Proc Natl Acad Sci USA 91, 1087810882.CrossRefGoogle Scholar
Lee, Y, Hirose, H, Zhou, YT, Esser, V, McGarry, JD & Unger, RH (1997) Increased lipogenic capacity of the islets of obese rats: a role in the pathogenesis of NIDDM. Diabetes 46, 408413.CrossRefGoogle ScholarPubMed
Lewis, JF, Vranic, M, Harley, P & Giacca, A (1997) Fatty acids mediate the acute extrahepatic effects of insulin on hepatic glucose production in humans. Diabetes 46, 11111119.CrossRefGoogle ScholarPubMed
Malaisse, WJ, Malaisse-Lagae, F (1968) Stimulation of insulin secretion by non-carbohydrate metabolites. J Lab Clin Med 72, 438448.Google Scholar
Manco, M, Mingrone, G, Greco, AV, Capristo, E, Gniuli, D, De Gaetano, A & Gasbarrini, G (2000) Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides. Metabolism 49, 220224.CrossRefGoogle ScholarPubMed
Milburn, JL Jr, Hirose, H, Lee, YH, Nagasawa, Y, Ogawa, A, Ohneda, M, BeltrandelRio, H, Newgard, CB, Johnson, JH & Unger, RH (1995) Pancreatic beta-cells in obesity: evidence for induction of functional morphologic and metabolic abnormalities by increased long-chain fatty acids. J Biol Chem 270, 12951299.CrossRefGoogle ScholarPubMed
Mingrone, G, De Gaetano, A, Greco, AV, Capristo, E, Benedetti, G & Gasbarrini, G (1997) Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids. Diabetologia 40, 599605.CrossRefGoogle ScholarPubMed
Mingrone, G, Henriksen, FL, Greco, AV, Krogh, LN, Capristo, E, Gastaldelli, A, Castagneto, M, Ferrannini, E, Gasbarrini, G & Beck-Nielsen, H (1999) Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency. Diabetes 48, 12581263.CrossRefGoogle ScholarPubMed
Oakes, ND, Bell, KS, Furler, SM, Camilleri, S, Saha, AK & Ruderman, NB (1997) Diet-induced muscle insulin resistance in rats is ameliorated by acute dietary lipid withdrawal or a single bout of exercise: parallel relationship between insulin stimulation of glucose uptake and suppression of long-chain fatty acyl-CoA. Diabetes 46, 20222028.CrossRefGoogle ScholarPubMed
Pan, DA, Lillioja, S, Kriketos, AD, Milner, MR, Baur, LA, Bogardus, C, Jenkins, AB & Storlien, LH (1997) Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46, 983988.CrossRefGoogle ScholarPubMed
Paolisso, G, Gambardella, A, Amato, L, Tortoriello, R, D'Amore, A, Varricchio, M & D'Onofrio, F (1995) Opposite effects of short- and long-term fatty acid infusion on insulin secretion in healthy subjects. Diabetologia 38, 12951299.CrossRefGoogle Scholar
Passi, S, Rothschild-Boros, MC, Fasella, P, Nazzaro-Porro, M & Whitehouse, D (1981) An application of high performance liquid chromatography to analysis of lipids in archaeological samples. J Lip Res 22, 778784.CrossRefGoogle ScholarPubMed
Polonsky, K, Frank, B, Pugh, W, Addis, A, Karrison, T, Meier, P, Tager, H & Rubenstein, A (1986) The limitations to and valid use of C-peptide as a marker of the secretion of insulin. Diabetes 35, 379389.CrossRefGoogle ScholarPubMed
Polonsky, K, Given, BD, Hirsh, LJ, Shapiro, ET, Tillil, H, Beebe, C, Galloway, J, Frank, B, Karrison, T & VanCauter, E (1988) Quantitative study of insulin secretion and clearance in normal and obese subjects. J Clin Invest 81, 435441.CrossRefGoogle ScholarPubMed
Prentki, M & Corkey, BE (1996) Are the beta-cell signaling molecules malonyl-CoA and cytosolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM?. Diabetes 45, 273283.CrossRefGoogle ScholarPubMed
Roden, M, Price, TB, Perseghin, G, Petersen, KF, Rothman, DL, Cline, GW & Shulman, GI (1996) Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 97, 28592865.CrossRefGoogle ScholarPubMed
Stein, DT, Esser, V, Stevenson, BE, Lane, KE, Whiteside, JH, Daniels, MB, Chen, S & McGarry, JD (1996) Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat. J Clin Invest 97, 27282735.CrossRefGoogle ScholarPubMed
Stein, DT, Stevenson, BE, Chester, MW, Basit, M, Daniels, MB, Turley, SD & McGarry, JD (1997) The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. J Clin Invest 100, 398403.CrossRefGoogle ScholarPubMed
Unger, RH (1995) Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes 44, 863870.CrossRefGoogle ScholarPubMed
van Cauter, E, Mestrez, F, Sturis, J & Polonsky, KS (1992) Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 41, 368377.CrossRefGoogle ScholarPubMed
Vessby, B, Unsitupa, M & Hermansen, H (2001) KANWU Study. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study. Diabetologia 44, 312319.CrossRefGoogle ScholarPubMed
Warnotte, C, Gilon, P, Nenquin, M & Henquin, JC (1994) Mechanisms of the stimulation of insulin release by saturated fatty acids. A study of palmitate effects in mouse beta-cells. Diabetes 43, 703711.CrossRefGoogle ScholarPubMed
World Health Organization World Health Organization (2002) Globalization Diet and Non Communicable Diseases Geneva World Health Organization (NLM Classification QT 235).Google Scholar