In humans at least seventy-five percent of insulin secretion arises
from punctuated insulin secretory bursts.
P[stod]orksen, Niels, Birgit Nyholm, Johannes D. Veldhuis, Peter C.
Butler, Ole Schmitz.
Department of Endocrinology and Metabolism M, Aarhus University
Hospital, Aarhus, Denmark, Department of Medicine, University of
Virginia, and NSF Center for Biological Timing, Charlottesville, VA,
22908, and Department of Medicine, The University of Edinburgh,
Edinburgh, Scotland
APStracts 4:0161E, 1997.
Detection of insulin secretory bursts in peripheral blood is hampered
by hepatic insulin extraction, dilution in systemic insulin pool and
time-delayed damping of secretory burst amplitude. Previous studies
in dogs in vivo and other experiments in vitro have shown that
approximately 70 % of all insulin is released within distinct insulin
secretory bursts. To establish a method for detection and
quantification of pulsatile insulin release in humans based on
peripheral insulin concentration measurements, we used a high
-sensitivity, specificity and precision insulin ELISA, and optimized
an established deconvolution methodology to quantify the frequency,
mass and amplitude of insulin secretory bursts, as well as estimate
the relative contribution of pulsatile insulin release to overall
insulin secretion. Using minutely sampled serum insulin
concentrations measured by a highly sensitive insulin ELISA, and
insulin kinetics of 2.8 minutes (first half life), 5.0 minutes
(second half life) and a fractional slow component of 0.28, the
deconvolved insulin secretion rates in 20 healthy subjects during
glucose infusion (4.5 mg/kg/min) could be resolved into a series (4.7
+/-0.1 minute/pulse) of approximately symmetric insulin secretory
bursts with a mean mass of 87 +/-12 pmol/L/pulse and a mean amplitude
(maximal release rate) of 35 +/-4.7 pmol/L/minute. The relative
contribution of pulsatile to overall insulin secretion was 75 +/-1.6
% (range 59 to 85 %). We conclude that in vivo insulin secretion in
the human during nominal glucose stimulation consists of a series of
punctuated insulin secretory bursts accounting for at least 75 % of
total insulin secretion.
Received 27 February 1997; accepted in final form 21 July 1997.
APS Manuscript Number E92-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997