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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Aug;90(2):545–553. doi: 10.1172/JCI115893

Low- and high-frequency insulin secretion pulses in normal subjects and pancreas transplant recipients: role of extrinsic innervation.

G E Sonnenberg 1, R G Hoffmann 1, C P Johnson 1, A H Kissebah 1
PMCID: PMC443133  PMID: 1644923

Abstract

Low-frequency ultradian and high-frequency insulin secretion pulses were studied in normal subjects and in metabolically stable pancreas transplant recipients. Insulin secretion pulsatility was evaluated after deconvoluting the pulsatile plasma C peptide concentrations with its kinetic coefficients. In normal subjects, ultradian insulin secretion pulses with periodicities of 75-115 min were consistently observed during the 24-h secretory cycle. Pulse period and relative amplitude during the overnight rest (95 +/- 4 min and 27.6 +/- 2.4%) were similar to those during the steady state of continuous enteral feeding (93 +/- 5 min and 32.6 +/- 3.3%). Sampling at 2-min intervals revealed the presence of high-frequency insulin secretion pulses with periodicities of 14-20 min and an average amplitude of 46.6 +/- 5.4%. Pancreas transplant recipients had normal fasting and fed insulin secretion rates. Both low- and high-frequency insulin secretion pulses were present. The high-frequency pulse characteristics were identical to normal. Low-frequency ultradian pulse periodicity was normal but pulse amplitude was increased. Thus, ultradian insulin secretory pulsatility is a consistent feature in normal subjects. The low- and high-frequency secretion pulsatilities are generated independent of extrinsic innervation. Autonomic innervation might modulate low-frequency ultradian pulse amplitude exerting a dampening effect.

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Selected References

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  1. Albertsson-Wikland K., Rosberg S., Libre E., Lundberg L. O., Groth T. Growth hormone secretory rates in children as estimated by deconvolution analysis of 24-h plasma concentration profiles. Am J Physiol. 1989 Dec;257(6 Pt 1):E809–E814. doi: 10.1152/ajpendo.1989.257.6.E809. [DOI] [PubMed] [Google Scholar]
  2. Bratusch-Marrain P. R., Komjati M., Waldhäusl W. K. Efficacy of pulsatile versus continuous insulin administration on hepatic glucose production and glucose utilization in type I diabetic humans. Diabetes. 1986 Aug;35(8):922–926. doi: 10.2337/diab.35.8.922. [DOI] [PubMed] [Google Scholar]
  3. Eaton R. P., Allen R. C., Schade D. S., Erickson K. M., Standefer J. Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior. J Clin Endocrinol Metab. 1980 Sep;51(3):520–528. doi: 10.1210/jcem-51-3-520. [DOI] [PubMed] [Google Scholar]
  4. Field J. B. Extraction of insulin by liver. Annu Rev Med. 1973;24:309–314. doi: 10.1146/annurev.me.24.020173.001521. [DOI] [PubMed] [Google Scholar]
  5. Goodner C. J., Hom F. G., Koerker D. J. Hepatic glucose production oscillates in synchrony with the islet secretory cycle in fasting rhesus monkeys. Science. 1982 Mar 5;215(4537):1257–1260. doi: 10.1126/science.7036347. [DOI] [PubMed] [Google Scholar]
  6. Goodner C. J., Sweet I. R., Harrison H. C., Jr Rapid reduction and return of surface insulin receptors after exposure to brief pulses of insulin in perifused rat hepatocytes. Diabetes. 1988 Oct;37(10):1316–1323. doi: 10.2337/diab.37.10.1316. [DOI] [PubMed] [Google Scholar]
  7. Goodner C. J., Walike B. C., Koerker D. J., Ensinck J. W., Brown A. C., Chideckel E. W., Palmer J., Kalnasy L. Insulin, glucagon, and glucose exhibit synchronous, sustained oscillations in fasting monkeys. Science. 1977 Jan 14;195(4274):177–179. doi: 10.1126/science.401543. [DOI] [PubMed] [Google Scholar]
  8. Guardabasso V., De Nicolao G., Rocchetti M., Rodbard D. Evaluation of pulse-detection algorithms by computer simulation of hormone secretion. Am J Physiol. 1988 Dec;255(6 Pt 1):E775–E784. doi: 10.1152/ajpendo.1988.255.6.E775. [DOI] [PubMed] [Google Scholar]
  9. Hansen B. C., Jen K. C., Belbez Pek S., Wolfe R. A. Rapid oscillations in plasma insulin, glucagon, and glucose in obese and normal weight humans. J Clin Endocrinol Metab. 1982 Apr;54(4):785–792. doi: 10.1210/jcem-54-4-785. [DOI] [PubMed] [Google Scholar]
  10. Hansen B. C., Jen K. L., Pek S. B., Wolfe R. A. Fluctuations in basal plasma levels of pancreatic polypeptide in monkeys and humans. Am J Physiol. 1985 Jun;248(6 Pt 2):R739–R747. doi: 10.1152/ajpregu.1985.248.6.R739. [DOI] [PubMed] [Google Scholar]
  11. Hindmarsh P. C., Matthews D. R., Brain C., Pringle P. J., Brook C. G. The application of deconvolution analysis to elucidate the pulsatile nature of growth hormone secretion using a variable half-life of growth hormone. Clin Endocrinol (Oxf) 1990 Jun;32(6):739–747. doi: 10.1111/j.1365-2265.1990.tb00920.x. [DOI] [PubMed] [Google Scholar]
  12. Jaspan J. B., Lever E., Polonsky K. S., Van Cauter E. In vivo pulsatility of pancreatic islet peptides. Am J Physiol. 1986 Aug;251(2 Pt 1):E215–E226. doi: 10.1152/ajpendo.1986.251.2.E215. [DOI] [PubMed] [Google Scholar]
  13. Katz H., Homan M., Velosa J., Robertson P., Rizza R. Effects of pancreas transplantation on postprandial glucose metabolism. N Engl J Med. 1991 Oct 31;325(18):1278–1283. doi: 10.1056/NEJM199110313251804. [DOI] [PubMed] [Google Scholar]
  14. Lang D. A., Matthews D. R., Burnett M., Ward G. M., Turner R. C. Pulsatile, synchronous basal insulin and glucagon secretion in man. Diabetes. 1982 Jan;31(1):22–26. doi: 10.2337/diab.31.1.22. [DOI] [PubMed] [Google Scholar]
  15. Lang D. A., Matthews D. R., Peto J., Turner R. C. Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. N Engl J Med. 1979 Nov 8;301(19):1023–1027. doi: 10.1056/NEJM197911083011903. [DOI] [PubMed] [Google Scholar]
  16. Longo E. A., Tornheim K., Deeney J. T., Varnum B. A., Tillotson D., Prentki M., Corkey B. E. Oscillations in cytosolic free Ca2+, oxygen consumption, and insulin secretion in glucose-stimulated rat pancreatic islets. J Biol Chem. 1991 May 15;266(14):9314–9319. [PubMed] [Google Scholar]
  17. Marshall J. C., Kelch R. P. Gonadotropin-releasing hormone: role of pulsatile secretion in the regulation of reproduction. N Engl J Med. 1986 Dec 4;315(23):1459–1468. doi: 10.1056/NEJM198612043152306. [DOI] [PubMed] [Google Scholar]
  18. Matthews D. R., Naylor B. A., Jones R. G., Ward G. M., Turner R. C. Pulsatile insulin has greater hypoglycemic effect than continuous delivery. Diabetes. 1983 Jul;32(7):617–621. doi: 10.2337/diab.32.7.617. [DOI] [PubMed] [Google Scholar]
  19. Nghiem D. D., Corry R. J. Technique of simultaneous renal pancreatoduodenal transplantation with urinary drainage of pancreatic secretion. Am J Surg. 1987 Apr;153(4):405–406. doi: 10.1016/0002-9610(87)90588-5. [DOI] [PubMed] [Google Scholar]
  20. Oerter K. E., Guardabasso V., Rodbard D. Detection and characterization of peaks and estimation of instantaneous secretory rate for episodic pulsatile hormone secretion. Comput Biomed Res. 1986 Apr;19(2):170–191. doi: 10.1016/0010-4809(86)90014-5. [DOI] [PubMed] [Google Scholar]
  21. Peiris A. N., Mueller R. A., Smith G. A., Struve M. F., Kissebah A. H. Splanchnic insulin metabolism in obesity. Influence of body fat distribution. J Clin Invest. 1986 Dec;78(6):1648–1657. doi: 10.1172/JCI112758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Polonsky K. S., Given B. D., 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. doi: 10.1172/JCI113339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Polonsky K. S., Licinio-Paixao J., Given B. D., 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. doi: 10.1172/JCI112308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rodbard D. Statistical quality control and routine data processing for radioimmunoassays and immunoradiometric assays. Clin Chem. 1974 Oct;20(10):1255–1270. [PubMed] [Google Scholar]
  25. Santen R. J., Bardin C. W. Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms. J Clin Invest. 1973 Oct;52(10):2617–2628. doi: 10.1172/JCI107454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shapiro E. T., Tillil H., Polonsky K. S., Fang V. S., Rubenstein A. H., 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. doi: 10.1210/jcem-67-2-307. [DOI] [PubMed] [Google Scholar]
  27. 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. doi: 10.1210/jcem-64-4-669. [DOI] [PubMed] [Google Scholar]
  28. Stagner J. I., Samols E. Perturbation of insulin oscillations by nerve blockade in the in vitro canine pancreas. Am J Physiol. 1985 May;248(5 Pt 1):E516–E521. doi: 10.1152/ajpendo.1985.248.5.E516. [DOI] [PubMed] [Google Scholar]
  29. Stagner J. I., Samols E. Role of intrapancreatic ganglia in regulation of periodic insular secretions. Am J Physiol. 1985 May;248(5 Pt 1):E522–E530. doi: 10.1152/ajpendo.1985.248.5.E522. [DOI] [PubMed] [Google Scholar]
  30. Stagner J. I., Samols E., Weir G. C. Sustained oscillations of insulin, glucagon, and somatostatin from the isolated canine pancreas during exposure to a constant glucose concentration. J Clin Invest. 1980 Apr;65(4):939–942. doi: 10.1172/JCI109750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Veldhuis J. D., Evans W. S., Rogol A. D., Drake C. R., Thorner M. O., Merriam G. R., Johnson M. L. Intensified rates of venous sampling unmask the presence of spontaneous, high-frequency pulsations of luteinizing hormone in man. J Clin Endocrinol Metab. 1984 Jul;59(1):96–102. doi: 10.1210/jcem-59-1-96. [DOI] [PubMed] [Google Scholar]
  32. Veldhuis J. D., Johnson M. L. Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol. 1986 Apr;250(4 Pt 1):E486–E493. doi: 10.1152/ajpendo.1986.250.4.E486. [DOI] [PubMed] [Google Scholar]
  33. Veldhuis J. D., Urban R. J., Beitins I. Z., Blizzard R. M., Johnson M. L., Dufau M. L. Pathophysiological features of the pulsatile secretion of biologically active luteinizing hormone in man. J Steroid Biochem. 1989 Oct;33(4B):739–749. doi: 10.1016/0022-4731(89)90486-x. [DOI] [PubMed] [Google Scholar]
  34. Weigle D. S. Pulsatile secretion of fuel-regulatory hormones. Diabetes. 1987 Jun;36(6):764–775. doi: 10.2337/diab.36.6.764. [DOI] [PubMed] [Google Scholar]

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