Effects of somatostatin on pulsatile insulin secretion; selective
inhibition of insulin burst mass.
Prksen, Niels, Stephen R. Munn, Jeffery L. Steers, Johannes D.
Veldhuis, Peter C. Butler.
Endocrine Research Unit, and Division of Transplant Surgery, Mayo
Clinic, Rochester, MN, 55905; Department of Medicine and NSF Center
for Biological Timing, University of Virginia Health Sciences Center,
Charlottesville, VA, 22908
APStracts 3:0025E, 1996.
While it is well known that somatostatin inhibits net insulin
secretion, it is unknown whether this is achieved by regulation of
the basal or pulsatile components of insulin secretion and, if the
latter, whether this is through modulation of pulse mass or
frequency. We addressed these questions with a canine model. Portal
vein blood was sampled at 1-minute intervals in 5 dogs for 60 minutes
before (basal) and 90 minutes following ingestion of 30 grams of
glucose (glucose) on two different occasions; during a saline (SAL)
or a somatostatin (175 ng/min) infusion (SMS). Plasma glucose
concentrations were similar during SAL and SMS. SMS had no effect on
pulse frequency before (8.4+/-0.7 vs 9.2+/-1.0 pulses/hour, SMS vs
SAL, p=0.54) or after glucose (13.3+/-1.1 vs 11.6+/-0.9 pulses/hour,
SMS vs SAL, p=0.22). In contrast, SMS decreased insulin pulse mass in
the postabsorptive (84+/-28 vs 214+/-73 pmol/pulse, SMS vs SAL,
p<0.05) and fed state (676+/-143 vs 913+/-183 pmol/pulse, SMS vs
SAL, p<0.05). In the postabsorptive state, SMS decreased insulin
clearance by 50% (0.32+/-0.04 vs 0.60+/-0.09 L/min, p<0.05) but
after glucose ingestion insulin clearance was comparable during SMS
or SAL (0.72+/-0.04 vs 0.80+/-0.08 L/min, p=0.4). SMS appeared to
alter insulin clearance through modulation of insulin pulse amplitude
since in the postabsorptive state clearance was closely correlated to
the pulse amplitude (r=+0.87, p<0.0001). In conclusion,
somatostatin regulates the rate of insulin secretion by selective
inhibition of pulsatile insulin secretion. Regulation of secretory
burst mass (and amplitude) may secondarily influence transhepatic and
thus total-body clearance of endogenously secreted insulin and
thereby serve as a novel mechanism to dictate the systemic insulin
concentration.
Received 23 October 1995; accepted in final form 12 January 1996.
APS Manuscript Number E510-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96