, Volume 39, Issue 5, pp 564–572 | Cite as

Alterations in the ultradian oscillations of insulin secretion and plasma glucose in aging

  • A. J. Scheen
  • J. Sturis
  • K. S. Polonsky
  • E. Van Cauter


Normal insulin secretion includes oscillations with a period length of 80–150 min which are tightly coupled to glucose oscillations of similar period. To determine whether normal aging is associated with alterations in these ultradian oscillations, eight, modestly overweight, older men (65±5 years) and eight weight-matched young control subjects (25±4 years) were studied during 53 h of constant glucose infusion. Blood samples were collected every 20 min and insulin secretion rates were calculated by deconvolution. Ultradian oscillations of glucose and insulin secretion were evident in both groups. Pulse frequency was similar for glucose and insulin secretion, and was not affected by age. The absolute amplitude of the glucose oscillations was similar in both groups but their relative amplitude was slightly dampened in the older adults. Both the absolute and the relative amplitudes of insulin secretory oscillations were markedly reduced in the older subjects. The normal linear increase in the amplitude of insulin oscillations occurring with increasing amplitudes of glucose oscillations was still present in the older adults but analysis of covariance indicated that the slope was significantly lower than in the young control subjects (p<0.0005), reflecting a decreased responsiveness of the beta cell to glucose changes. The temporal concordance between insulin and glucose oscillations, as estimated by pulse concomitancy and cross-correlation, was also lower in older subjects. The similarities between the alterations in the ultradian oscillations of insulin secretion and glucose in older healthy adults and those occurring in diabetic patients suggest that an impairment of beta-cell function may play a primary role in the deterioration of glucose tolerance in aging.


Aging ultradian oscillations insulin secretion glucose tolerance pulsatility beta cell feedback loop diabetes mellitus 



Non-insulin dependent diabetes mellitus


rapid-eye movement


insulin secretion rate


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Broughton DL, Taylor R (1991) Deterioration of glucose tolerance with age: the role of insulin resistance. Age Ageing 20: 221–225Google Scholar
  2. 2.
    Blackman MR, Elahi D, Harman SH (1994) Endocrinology and aging. In: DeGroot LJ (ed) Endocrinology. Saunders, Philadelphia, pp 2702–2730Google Scholar
  3. 3.
    Paolisso G, Scheen A, Lefèbvre P (1995) Glucose handling, diabetes and ageing. Horm Res 43: 52–57Google Scholar
  4. 4.
    Shimokata H, Muller DC, Fleg JL, Sorkin J, Ziemba AW, Andres R (1991) Age as independent determinant of glucose tolerance. Diabetes 40: 44–51Google Scholar
  5. 5.
    Fink RI, Kolterman OG, Griffin J, Olefsky JM (1983) Mechanisms of insulin resistance in aging. J Clin Invest 71: 1523–1535Google Scholar
  6. 6.
    Rowe JW, Minaker KL, Pallotta JA, Flier JS (1983) Characterization of the insulin resistance of aging. J Clin Invest 71: 1581–1587Google Scholar
  7. 7.
    Chen M, Bergman RN, Pacini G, Porte D (1985) Pathogenesis of age related glucose intolerance in man: insulin resistance and decreased beta cell function. J Clin Endocrinol Metab 60: 13–20Google Scholar
  8. 8.
    Gumbiner B, Polonsky KS, Beltz WF, Wallace P, Brechtel G, Fink RI (1989) Effects of aging on insulin secretion. Diabetes 38: 1549–1556Google Scholar
  9. 9.
    Lang DA, Matthews DR, Peto J, Turner RC (1979) Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. N Engl J Med 301: 1023–1027Google Scholar
  10. 10.
    Hansen BC, Schielke G, Jen K-L, Wolfe R, Movahed H, Pek S (1982) Rapid fluctuations in plasma catecholamines in monkeys under undisturbed conditions. Am J Physiol 242:E40-E46Google Scholar
  11. 11.
    Shapiro ET, Tillil H, Polonsky KS, Fang VS, Rubenstein AH, Van Cauter E (1988) Oscillations in insulin secretion during constant glucose infusion in normal man: relationship to changes in plasma glucose. J Clin Endocrinol Metab 67: 307–314Google Scholar
  12. 12.
    Simon C, Brandenberger G, Follenius M (1987) Ultradian oscillations of plasma glucose, insulin, and C-peptide in man during continuous enterai nutrition. J Clin Endocrinol Metab 64: 669–674Google Scholar
  13. 13.
    Sturis J, O'Meara NM, Shapiro ET et al. (1993) Differential effects of glucose stimulation upon rapid pulses and ultradian oscillations of insulin secretion. J Clin Endocrinol Metab 76: 895–901Google Scholar
  14. 14.
    Sturis J, Polonsky KS, Shapiro ET, Blackman JD, O'Meara NM, Van Cauter E (1992) Abnormalities in the ultradian oscillations of insulin secretion and glucose levels in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 35: 681–689Google Scholar
  15. 15.
    Lefèbvre PJ, Paolisso G, Scheen AJ, Henquin JC (1987) Pulsatility of insulin and glucagon release physiological significance and pharmacological implications. Diabetologia 30: 443–452Google Scholar
  16. 16.
    Sturis J, Scheen AJ, Leproult R, Polonsky KS, Van Cauter E (1995) 24-hour glucose profiles during continuous or oscillatory insulin infusion: demonstration of the functional significance of ultradian insulin oscillations. J Clin Invest 95: 1464–1471Google Scholar
  17. 17.
    Matthews DR, Frank M, Jackson R, Toescu V, Alam S (1988) Normal regular insulin oscillations are absent in gross obesity, old age and mild and severe type 2 (non-insulin-dependent) diabetes. Diabetologia 31: 519A (Abstract)Google Scholar
  18. 18.
    Paolisso G, Salvatore T, Sgambato S, Torella R, Varricchio M, D'Onofrio F (1990) Metabolie effects of pulsatile insulin infusion in the elderly. Acta Endocrinol 123: 19–23Google Scholar
  19. 19.
    Polonsky KS, Given BD, Hirsch LJ et al. (1988) Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med 318: 1231–1239Google Scholar
  20. 20.
    Simon C, Brandenberger G, Follenius M, Schlienger JL (1991) Alteration in the temporal organisation of insulin secretion in type 2 (non-insulin-dependent) diabetic patients under continuous enteral nutrition. Diabetologia 34: 435–440Google Scholar
  21. 21.
    Sturis J, Van Cauter E, Blackman JD, Polonsky KS (1991) Entrainment of pulsatile insulin secretion by oscillatory glucose infusion. J Clin Invest 87: 439–445Google Scholar
  22. 22.
    O'Meara NM, Sturis J, Van Cauter E, Polonsky KS (1993) Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin-dependent diabetes mellitus. J Clin Invest 92: 262–271Google Scholar
  23. 23.
    Frank SA, Roland DC, Sturis J et al. (1995) Effects of aging on glucose tolerance during wakefulness and during sleep. Am J Physiol (Endocrinology and Metabolism) 269:E1006-E1016Google Scholar
  24. 24.
    Rechtschaffen A, Kales A (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Government Printing Office, Washington, DCGoogle Scholar
  25. 25.
    Van Cauter E, Blackman JD, Roland D, Spire JP, Refetoff S, Polonsky KS (1991) Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep. J Clin Invest 88: 934–942Google Scholar
  26. 26.
    Morgan CR, Lazarow A (1963) Immunoassay of insulin: two antibody system: plasma insulin levels of normal, subdiabetic and diabetic rats. Diabetes 12: 115–126Google Scholar
  27. 27.
    Faber OK, Binder C, Markussen J et al. (1978) Characterization of seven C-peptide antisera. Diabetes 27 [Suppl 1]: 170–177Google Scholar
  28. 28.
    Polonsky KS, Licinio-Paixao J, Given BD et al. (1986) Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest 77: 98–105Google Scholar
  29. 29.
    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: 368–377Google Scholar
  30. 30.
    Van Cauter E, Polonsky KS, Blackman JD et al. (1994) Abnormal temporal patterns of glucose tolerance in obesity: relationship to sleep-related growth hormone and circadian cortisol rhythmicity. J Clin Endocrinol Metab 79: 1797–1805Google Scholar
  31. 31.
    Cleveland WS (1979) Robust locally weighted regression and smoothing scatterplots. J Am Stat Assoc 74: 829–836Google Scholar
  32. 32.
    Jenkins GM, Watts DG (1968) Spectral analysis and its application. Holden Day, San FranciscoGoogle Scholar
  33. 33.
    Van Cauter E (1988) Estimating false-positive and false-negative errors in analyses of hormonal pulsatility. Am J Physiol 254:E786-E794Google Scholar
  34. 34.
    Polonsky KS, Given BD, Van Cauter E (1988) Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 81: 442–448Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • A. J. Scheen
    • 1
  • J. Sturis
    • 2
  • K. S. Polonsky
    • 2
  • E. Van Cauter
    • 2
  1. 1.Division of Diabetes, Nutrition and Metabolic Diseases, Department of MedicineUniversity of LiègeLiègeBelgium
  2. 2.Section of Endocrinology, Department of MedicineUniversity of ChicagoUSA

Personalised recommendations