Regulatory role of intraislet somatostatin on insulin secretion in the isolated perfused human pancreas.
This study was undertaken to determine whether intraislet somatostatin inhibits insulin secretion in the human islet. A high-affinity monoclonal somatostatin antibody was used to immunoneutralize somatostatin in the isolated, perfused human pancreas. Single pass perfusion was performed in pancreata obtained from cadaveric organ donors using a modified Krebs medium with either 3.9 or 12.9 mM glucose. Sequential test periods separated by basal periods were performed with either somatostatin-14 (SS-14), somatostatin monoclonal antibody (CURE.S6), or a combined infusion. Infusion of SS-14 resulted in inhibition of insulin secretion under both low glucose (delta X = -712 +/- 212 pM) (p < 0.05) and high glucose (delta X = -21,913 +/- 10,003 pM) (p = 0.06) conditions. Immunoneutralization of intraislet somatostatin with CURE.S6 resulted in a significant increase in insulin secretion under both low glucose (454 +/- 162 pM) (p < 0.05) and high glucose (2,177 +/- 829 pM) (p < 0.05) conditions. Combined infusion of SS-14 and CURE.S6 resulted in a reversal of the inhibitory effect of exogenous SS-14. The data suggest that intraislet somatostatin has an inhibitory role in the regulation of insulin secretion in the human islet.
Kleinman
R
R
Department of Surgery, VAMC-West Los Angeles.
Ohning
G
G
Wong
H
H
Watt
P
P
Walsh
J
J
Brunicardi
F C
FC
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D002648:Child; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007263:Infusions, Parenteral; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D013004:Somatostatin / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007328:Insulin; D013004:Somatostatin; D005947:Glucose