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Am J Physiol Endocrinol Metab 278: E484-E490, 2000;
0193-1849/00 $5.00
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Vol. 278, Issue 3, E484-E490, March 2000

High-frequency oscillations in circulating amylin concentrations in healthy humans

Claus B. Juhl1, Niels Pørksen1, Jeppe Sturis2, Åge Prange Hansen3, Johannes D. Veldhuis4, Steven Pincus5, Mark Fineman6, and Ole Schmitz1

1 Department of Medicine M (Endocrinology and Diabetes), Århus Kommunehospital, University Hospital of Aarhus, 8000 Århus; 2 Novo Nordisk, 2880 Bagsvaerd; and 3 Department of Medicine, Kolding Sygehus, 6000 Kolding, Denmark; 4 Endocrinology Division, National Science Foundation Center for Biological Timing, University of Virginia, Charlottesville, Virginia 22908; 5 Guilford, Connecticut; and 6 Amylin Pharmaceuticals, San Diego, California 92121

Amylin is stored in the pancreatic beta -cell granules and cosecreted with insulin in response to nutrient stimuli. To gain further insight into control of hormonal release in beta -cell physiology, we examined whether amylin, like insulin, circulates in a high-frequency oscillatory pattern, and if it does, to compare the secretory patterns of the two hormones. Eight overnight-fasted healthy individuals were studied during intravenous glucose infusion (2.0 mg · kg-1 · min-1). Blood was collected every minute for 90 min and analyzed in triplicate for amylin, total amylin immunoreactivity (TAI), and insulin. Mean plasma concentrations of amylin (nonglycosylated), TAI (nonglycosylated plus glycosylated), insulin, and glucose were 2.77 ± 1.21 pmol/l, 7.60 ± 1.73 pmol/l, 50.4 ± 17.5 pmol/l, and 5.9 ± 0.3 mmol/l, respectively. The 90-min time series of amylin, TAI, and insulin were analyzed for periodicity (by spectral analysis, autocorrelation analysis, and deconvolution analysis) and regularity [by approximate entropy (ApEn)]. Significant spectral density peaks were demonstrated by a random shuffling technique in 7 (out of 7), 8 (out of 8), and 8 (out of 8) time series, respectively, whereas autocorrelation analysis revealed significant pulsatility in 5 (out of 7), 7 (out of 8), and 5 (out of 8), respectively. The dominant periodicity of oscillations determined by spectral analysis was 4.6 ± 0.3, 4.6 ± 0.4, and 6.5 ± 1.1 min/pulse, respectively (amylin vs. insulin, P = 0.017, TAI vs. insulin, P = 0.018). By deconvolution analysis, amylin and insulin periodicities were, respectively, 6.3 ± 1.0 and 5.5 ± 0.6 min. By application of the regularity statistic, ApEn, 6 (out of 7), 7 (out of 8), and 6 (out of 8), respectively, were found to be significantly different from random. In conclusion, like several other hormones, circulating amylin concentrations exhibit oscillations in the secretory patterns for nonglycosylated as well as glycosylated forms. Whether the high-frequency pulsatile release of amylin is disturbed in diabetes is not known.

amylin secretion; insulin secretion; amylin pulsatility


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O. Schmitz, B. Brock, and J. Rungby
Amylin Agonists: A Novel Approach in the Treatment of Diabetes
Diabetes, December 1, 2004; 53(suppl_3): S233 - S238.
[Abstract] [Full Text] [PDF]




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