Effects of somatostatin on pulsatile insulin secretion: elective inhibition of insulin burst mass.
Although 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-min intervals in five dogs for 60 min before (basal) and 90 min after ingestion of 30 g glucose on two different occasions, during a saline (SAL) or a somatostatin (SMS, 175 ng/min) infusion. 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/h, SMS vs. SAL, P = 0.54) or after glucose (13.3 +/- 1.1 vs. 11.6 +/- 0.9 pulses/h, 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 states (676 +/- 143 vs. 913 +/- 183 pmol/pulse, SMS vs. SAL, P < 0.05). In the postabsorptive state, SMS decreased insulin clearance by approximately 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, because 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.
Pørksen
N
N
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
Munn
S R
SR
Steers
J L
JL
Veldhuis
J D
JD
Butler
P C
PC
D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D005215:Fasting; D005947:Glucose / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology*; D000078790:Insulin Secretion; D008297:Male; D011673:Pulsatile Flow; D012965:Sodium Chloride / Q000494:pharmacology; D012996:Solutions; D013004:Somatostatin / Q000494:pharmacology*
D007328:Insulin; D007329:Insulin Antagonists; D012996:Solutions; D012965:Sodium Chloride; D013004:Somatostatin; D005947:Glucose