• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Sep 1991; 88(3): 934–942.
PMCID: PMC295490

Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.

Abstract

To define the roles of circadian rhythmicity (intrinsic effects of time of day independent of the sleep or wake condition) and sleep (intrinsic effects of the sleep condition, irrespective of the time of day) on the 24-h variation in glucose tolerance, eight normal men were studied during constant glucose infusion for a total of 53 h. The period of study included 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples for the measurement of glucose, insulin, C-peptide, cortisol, and growth hormone were collected at 20-min intervals throughout the entire study. Insulin secretion rates were derived from C-peptide levels by deconvolution. Sleep was polygraphically monitored. During nocturnal sleep, levels of glucose and insulin secretion increased by 31 +/- 5% and 60 +/- 11%, respectively, and returned to baseline in the morning. During sleep deprivation, glucose levels and insulin secretion rose again to reach a maximum at a time corresponding to the beginning of the habitual sleep period. The magnitude of the rise above morning levels averaged 17 +/- 5% for glucose and 49 +/- 8% for calculated insulin secretion. Serum insulin levels did not parallel the circadian variation in insulin secretion, indicating the existence of an approximate 40% increase in insulin clearance during the night. Daytime sleep was associated with a 16 +/- 3% rise in glucose levels, a 55 +/- 7% rise in insulin secretion, and a 39 +/- 5% rise in serum insulin. The diurnal variation in insulin secretion was inversely related to the cortisol rhythm, with a significant correlation of the magnitudes of their morning to evening excursions. Sleep-associated rises in glucose correlated with the amount of concomitant growth hormone secreted. These studies demonstrate previously underappreciated effects of circadian rhythmicity and sleep on glucose levels, insulin secretion, and insulin clearance, and suggest that these effects could be partially mediated by cortisol and growth hormone.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Carroll KF, Nestel PJ. Diurnal variation in glucose tolerance and in insulin secretion in man. Diabetes. 1973 May;22(5):333–348. [PubMed]
  • Service FJ, Hall LD, Westland RE, O'Brien PC, Go VL, Haymond MW, Rizza RA. Effects of size, time of day and sequence of meal ingestion on carbohydrate tolerance in normal subjects. Diabetologia. 1983 Oct;25(4):316–321. [PubMed]
  • Verrillo A, De Teresa A, Martino C, Di Chiara G, Pinto M, Verrillo L, Torello F, Gattoni A. Differential roles of splanchnic and peripheral tissues in determining diurnal fluctuation of glucose tolerance. Am J Physiol. 1989 Oct;257(4 Pt 1):E459–E465. [PubMed]
  • Shapiro ET, Tillil H, Polonsky KS, Fang VS, Rubenstein AH, Van Cauter E. Oscillations in insulin secretion during constant glucose infusion in normal man: relationship to changes in plasma glucose. J Clin Endocrinol Metab. 1988 Aug;67(2):307–314. [PubMed]
  • Van Cauter E, Désir D, Decoster C, Féry F, Balasse EO. Nocturnal decrease in glucose tolerance during constant glucose infusion. J Clin Endocrinol Metab. 1989 Sep;69(3):604–611. [PubMed]
  • Faber OK, Binder C, Markussen J, Heding LG, Naithani VK, Kuzuya H, Blix P, Horwitz DL, Rubenstein AH. Characterization of seven C-peptide antisera. Diabetes. 1978;27 (Suppl 1):170–177. [PubMed]
  • Virasoro E, Copinschi G, Bruno OD, Leclerq R. Radioimmunoassay of human growth hormone using a charcoal-dextran separation procedure. Clin Chim Acta. 1971 Jan;31(1):294–297. [PubMed]
  • Polonsky KS, Licinio-Paixao J, Given BD, Pugh W, Rue P, Galloway J, Karrison T, Frank B. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest. 1986 Jan;77(1):98–105. [PMC free article] [PubMed]
  • Shapiro ET, Tillil H, Miller MA, Frank BH, Galloway JA, Rubenstein AH, Polonsky KS. Insulin secretion and clearance. Comparison after oral and intravenous glucose. Diabetes. 1987 Dec;36(12):1365–1371. [PubMed]
  • Simon C, Brandenberger G, Follenius M. Ultradian oscillations of plasma glucose, insulin, and C-peptide in man during continuous enteral nutrition. J Clin Endocrinol Metab. 1987 Apr;64(4):669–674. [PubMed]
  • Van Cauter E. Method for characterization of 24-h temporal variation of blood components. Am J Physiol. 1979 Sep;237(3):E255–E264. [PubMed]
  • Van Cauter E. Estimating false-positive and false-negative errors in analyses of hormonal pulsatility. Am J Physiol. 1988 Jun;254(6 Pt 1):E786–E794. [PubMed]
  • Golstein J, Van Cauter E, Désir D, Noël P, Spire JP, Refetoff S, Copinschi G. Effects of "jet lag" on hormonal patterns. IV. Time shifts increase growth hormone release. J Clin Endocrinol Metab. 1983 Mar;56(3):433–440. [PubMed]
  • Refetoff S, Sönksen PH. Disappearance rate of endogenous and exogenous human growth hormone in man. J Clin Endocrinol Metab. 1970 Mar;30(3):386–392. [PubMed]
  • Turek FW. Circadian neural rhythms in mammals. Annu Rev Physiol. 1985;47:49–64. [PubMed]
  • Ho KY, Veldhuis JD, Johnson ML, Furlanetto R, Evans WS, Alberti KG, Thorner MO. Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. J Clin Invest. 1988 Apr;81(4):968–975. [PMC free article] [PubMed]
  • Vance ML, Thorner MO. Fasting alters pulsatile and rhythmic cortisol release in normal man. J Clin Endocrinol Metab. 1989 Jun;68(6):1013–1018. [PubMed]
  • Linsell CR, Lightman SL, Mullen PE, Brown MJ, Causon RC. Circadian rhythms of epinephrine and norepinephrine in man. J Clin Endocrinol Metab. 1985 Jun;60(6):1210–1215. [PubMed]
  • Weitzman ED, Zimmerman JC, Czeisler CA, Ronda J. Cortisol secretion is inhibited during sleep in normal man. J Clin Endocrinol Metab. 1983 Feb;56(2):352–358. [PubMed]
  • Reaven GM, Hollenbeck C, Jeng CY, Wu MS, Chen YD. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes. 1988 Aug;37(8):1020–1024. [PubMed]
  • Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest. 1988 Feb;81(2):442–448. [PMC free article] [PubMed]
  • Clore JN, Nestler JE, Blackard WG. Sleep-associated fall in glucose disposal and hepatic glucose output in normal humans. Putative signaling mechanism linking peripheral and hepatic events. Diabetes. 1989 Mar;38(3):285–290. [PubMed]
  • Orskov L, Schmitz O, Jørgensen JO, Arnfred J, Abildgaard N, Christiansen JS, Alberti KG, Orskov H. Influence of growth hormone on glucose-induced glucose uptake in normal men as assessed by the hyperglycemic clamp technique. J Clin Endocrinol Metab. 1989 Feb;68(2):276–282. [PubMed]
  • Møller N, Butler PC, Antsiferov MA, Alberti KG. Effects of growth hormone on insulin sensitivity and forearm metabolism in normal man. Diabetologia. 1989 Feb;32(2):105–110. [PubMed]
  • Vaitkus P, Sirek A, Norwich KH, Sirek OV, Unger RH, Harris V. Rapid changes in hepatic glucose output after a pulse of growth hormone in dogs. Am J Physiol. 1984 Jan;246(1 Pt 1):E14–E20. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...