Download PDF
Horm Metab Res 2001; 33(9): 548-553
DOI: 10.1055/s-2001-17208
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

Enhancement of β-Cell Sensitivity to Glucose by Oral Fat Load

O. Wuesten 1 , C. H. Balz 1 , H.-U. Kloer 1 , R. G. Bretzel 2 , T. Linn 2
  • 1 Division of Gastroenterology of Medical Clinic III and Policlinic of Justus Liebig University, Gießen, Germany
  • 2 Clinical Research Unit of Medical Clinic III and Policlinic of Justus Liebig University, Gießen, Germany
Further Information

Publication History

Publication Date:
17 September 2001 (online)

Also available at
    Permissions and Reprints

Recent studies have demonstrated that 6 h infusions of lipid emulsion enhance insulin release, whereas 24 h infusions inhibit insulin secretion. How insulin release is modulated after oral fat loading has not yet been elucidated. 17 healthy fasting volunteers were subjected to 3 experiments in random order: test 1 was a frequently sampled i. v. glucose tolerance test (FSIVGTT, 0.3 g/kg glucose), test 2 began with the ingestion of 50 % sunflower oil (1.5 g/kg) followed by FSIVGTT 4 h later. Test 3 was identical to test 2 with i. v. addition of 100 U/kg heparin prior to FSIVGTT. Glucose and insulin data were analyzed by minimal model assumptions - glucose sensitivity of the β-cells (Θ1), acute insulin response (AIR) (10 min), 3 h insulin release (Θ2), glucose threshold of insulin secretion (h), insulin degradation rate (n), peripheral insulin sensitivity (SI), and glucose-dependent glucose disposal (SG). After drinking the fat emulsion, FFAs increased to 0.8 ± 0.3 mmol/l (test 2) and to 3.0 ± 0.3 mmol/l (test 3). Moderately increased FFA concentrations were associated with elevation of Θ1 (test 1, control 335 ± 157 vs. test 2: 859 ± 612 pM × min × mM-1, p = 0.030). At high plasma FFA levels and in the presence of heparin (test 3), Θ1 was reduced compared to test 2 and unchanged compared to test 1. Θ2 and h were elevated in both tests 2 and 3 compared to test 1. No changes of n, SI and SG were found. In conclusion, the ingestion of sunflower oil triglyceride emulsion resulted in a 60 % increase in plasma free fatty acids and enhanced the capacity of β-cells to secrete insulin. Heparin-induced high levels of FFA further augmented the total insulin release and inhibited parameters of glucose responsiveness.

Key words:

β-cell - Oral Fat - Free Fatty Acids

References

  • 1 Karpe F, Steiner G, Uffelman K, Olivecrona T, Hamsten A. Postprandial lipoproteins and progression of coronary atherosclerosis.  Atherosclerosis. 1994;  106 83-97
    CrossrefPubMedGoogle Scholar
  • 2 Austin M A. Triacyglycerol and coronary heart disease.  Proc Nutr Soc. 1997;  56 667-670
    CrossrefPubMedGoogle Scholar
  • 3 Groot P HE, Stiphout W AHJ, Krauss X H, et al. Postprandial lipoprotein metabolism in normolipidemic men with and without coronary artery disease.  Arterioscler Thromb. 1991;  11 653-662
    PubMedGoogle Scholar
  • 4 Zilversmit D B. Atherogenesis: a postprandial phenomenon.  Circulation. 1979;  60 473-485
    CrossrefPubMedGoogle Scholar
  • 5 Reaven G M. Banting Lecture 1988: Role of insulin resistance in human disease.  Diabetes. 1988;  37 1595-1607
    CrossrefPubMedGoogle Scholar
  • 6 Schrezenmeir J, Fenselau S, Keppler I, et al. Postprandial triglyceride high response and the metabolic syndrome.  Ann N Y Acad Sci. 1997;  827 353-368
    PubMedGoogle Scholar
  • 7 Schrezenmeir J. Hyperinsulinemia, hyperproinsulinemia and insulin resistance in the metabolic syndrome.  Experientia. 1996;  52 426-432
    CrossrefPubMedGoogle Scholar
  • 8 Frayn K N, Williams C M, Arner P. Are increased plasma non-esterified fatty acid concentrations a risk marker for coronary heart disease and other chronic diseases?.  Clin Sci. 1996;  90 243-253
    PubMedGoogle Scholar
  • 9 Randle P J, Priestman D A, Mistry S, Halsall A. Mechanisms modifying glucose oxidation in diabetes mellitus.  Diabetologia. 1994;  37 S155-S161
    CrossrefPubMedGoogle Scholar
  • 10 Randle P J, Hales C N, Garland P B, Newsholme E A. The glucose fatty-acid cycle, its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus.  Lancet. 1963;  I 785-789
    PubMedGoogle Scholar
  • 11 Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM.  Diabetes. 1997;  46 3-10
    CrossrefPubMedGoogle Scholar
  • 12 McGarry J D. What if Minkowsky had been ageusic? An alternative angle on diabetes.  Science. 1992;  258 766-770
    CrossrefPubMedGoogle Scholar
  • 13 Reaven G M, Hollenbeck C, Jeng C Y, Wu M S, Chen Y D. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM.  Diabetes. 1988;  37 1020-1024
    CrossrefPubMedGoogle Scholar
  • 14 DeFronzo R A, Bonadonna R C, Ferrannini E. Pathogenesis of NIDDM. A balanced overview.  Diabetes Care. 1992;  15 318-368
    CrossrefPubMedGoogle Scholar
  • 15 Stein D T, Esser V, Stevenson B, et al. Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat.  J Clin Invest. 1996;  97 2728-2735
    CrossrefPubMedGoogle Scholar
  • 16 Pelkonen R, Miettinen T A, Taskinen M R, Nikkilä E A. Effect of acute elevation of plasma glycerol, triglyceride and FFA levels on glucose utilization and plasma insulin.  Diabetes. 1968;  17 76-82
    PubMedGoogle Scholar
  • 17 Balasse E O, Ooms H A. Role of plasma free fatty acids in the control of insulin secretion in man.  Diabetologia. 1973;  9 145-151
    CrossrefPubMedGoogle Scholar
  • 18 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. 1995;  38 1295-1299
    PubMedGoogle Scholar
  • 19 Boden G, Jadali F, White J, et al. Effects of fat on insulin-stimulated carbohydrate metabolism in normal men.  J Clin Invest. 1991;  88 960-966
    PubMedGoogle Scholar
  • 20 Zhou M Y, Grill V E. 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. 1994;  93 870-876
    CrossrefPubMedGoogle Scholar
  • 21 Stein D T, Stevenson B E, Chester M W, et al. The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.  J Clin Invest. 1997;  100 398-403
    CrossrefPubMedGoogle Scholar
  • 22 Boden G, Chen X, Iqbal N. Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects.  Diabetes. 1998;  47 1609-1612
    PubMedGoogle Scholar
  • 23 Dobbins R L, Chester M W, Daniels M B, McGarry J D, Stein D T. Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans.  Diabetes. 1998;  47 1613-1618
    PubMedGoogle Scholar
  • 24 Unger R H. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications.  Diabetes. 1995;  44 863-870
    PubMedGoogle Scholar
  • 25 Herrmann C, Goke R, Richter G, Fehmann H C, Arnold R, Goke B. Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients.  Digestion. 1995;  56 117-126
    CrossrefPubMedGoogle Scholar
  • 26 Creutzfeldt W, Ebert R, Willms B, Frerichs H, Brown J C. Gastric inhibitory polypeptide (GIP) and insulin in obesity: increased response to stimulation and defective feedback control of serum levels.  Diabetologia. 1978;  14 15-24
    CrossrefPubMedGoogle Scholar
  • 27 Brundin T. Whole body and splanchnic metabolic, circulatory, and thermal effects of oral vs. intravenous fat administration.  Am J Physiol. 1998;  274 E684-E691
    PubMedGoogle Scholar
  • 28 Lukaski H C. Body composition assessment using impedance methods. In: Björntorp P, Brodoff BN (eds). Obesity.  Philadelphia:; J. B. Lippincott Company, 1992: 67-79
    Google Scholar
  • 29 Bergman R N, Beard J C, Chen M. The minimal modeling method. Assessment of insulin sensitivity and beta-cell function in vivo. In: Clarke WL, Larner J, Pohl SL (eds). Methods in diabetes research.  New York:; John Wiley & Sons, 1986: 15-34
    Google Scholar
  • 30 Yang Y J, Hope I D, Ader M, Bergman R N. Insulin transport across capillaries is rate limiting for insulin action in dogs.  J Clin Invest. 1989;  84 1620-1628
    CrossrefPubMedGoogle Scholar
  • 31 Frayn K N, Shadid S, Hamlani R, et al. Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition.  Am J Physiol. 1994;  266 E308-E317
    PubMedGoogle Scholar
  • 32 Linn T, Ebener K, Laube H, Federlin K. Simultaneous assessment of A- and B-cell function in newly diagnosed insulin-dependent diabetes mellitus.  Endocrinol Metab. 1996;  3 117-123
    PubMedGoogle Scholar
  • 33 Seyffert W A, Madison L L. Physiologic effects of metabolic fuels on carbohydrate metabolism.  Diabetes. 1967;  16 765-776
    PubMedGoogle Scholar
  • 34 Dobbins R L, Chester M W, Daniels M B, Stein D T, McGarry J D. A fatty-acid dependend step is critically important for both glucose and non-glucose stimulated insulin secretion.  J Clin Invest. 1998;  101 2370-2376
    CrossrefPubMedGoogle Scholar
  • 35 Zhou Y P, Grill V. Long term exposure to fatty acids and ketones inhibits B-cell functions in human pancreatic islets of Langerhans.  J Clin Endocrinol Metab. 1995;  80 1584-1590
    CrossrefPubMedGoogle Scholar
  • 36 McGarry J D, Dobbins R L. Fatty acids, lipotoxicity and insulin secretion.  Diabetologia. 1999;  42 128-138
    CrossrefPubMedGoogle Scholar
  • 37 Hennes M M, Dua A, Kissebah A H. Effects of free fatty acids and glucose on splanchnic insulin dynamics.  Diabetes. 1997;  46 57-62
    PubMedGoogle Scholar
  • 38 Carroll K F, Nestel P J. Effect of long-chain triglyceride on human insulin secretion.  Diabetes. 1972;  21 923-929
    PubMedGoogle Scholar
  • 39 Kraegen E W, Chisholm D J, Young J D, Lazarus L. The gastrointestinal stimulus to insulin release.  J Clin Invest. 1970;  49 524-529
    CrossrefPubMedGoogle Scholar
  • 40 Ebert R, Frerichs H, Creutzfeldt W. Impaired feedback control of fat induced gastric inhibitory polypeptide (GIP) secretion by insulin in obesity and glucose intolerance.  Eur J Clin Invest. 1979;  9 129-135
    PubMedGoogle Scholar
  • 41 Thorell J, Persson B, Sterkey G. Effect of fat infusion on plasma glucose, FFA, glycerol and insulin levels during i. v. and oral glucose tolerance tests.  Diabetologia. 1966;  2 232
    PubMedGoogle Scholar
  • 42 Persson E, Nordenstrom J, Nilsson-Ehle P, Hagenfeldt L, Wahren J. Plasma lipolytic activity and substrate oxidation after intravenous administration of heparin and a low molecular weight heparin fragment.  Clin Physiol. 1990;  10 573-583
    PubMedGoogle Scholar
  • 43 Koyama K, Chen G, Lee Y, Unger R H. Tissue triglycerides, insulin resistance, and insulin production: implications for hyperinsulinemia of obesity.  Am J Physiol. 1997;  273 E708-E713
    PubMedGoogle Scholar
  • 44 Fernandez J, Valdeolmillos M. Increased levels of free fatty acids in fasted mice stimulate in vivo β-cell electrical activity.  Diabetes. 1998;  47 1707-1712
    PubMedGoogle Scholar

T. Linn,M.D. 

Clinical Research Unit
Medical Clinic III and Policlinic
University of Gießen

Rodthohl 6
35392 Gießen, Germany


Phone: + 49 (641) 99 42841

Fax: + 49 (641) 99 42879

Email: thomas.linn@innere.med.uni-giessen.de