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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
-cell granules and
cosecreted with insulin in response to nutrient stimuli. To gain
further insight into control of hormonal release in
-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
This article has been cited by other articles:
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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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