TY - JOUR
T1 - Intraislet Somatostatin Inhibits Insulin (Via a Subtype-2 Somatostatin Receptor) but Not Islet Amyloid Polypeptide Secretion in the Isolated Perfused Human Pancreas
AU - Atiya, Azmi W.
AU - Moldovan, Stephen
AU - Adrian, Thomas E.
AU - Coy, David
AU - Walsh, John
AU - Brunicardi, F. Charles
N1 - Funding Information:
From the Department of Surgery and CURE, VAMC-West Los Angeles, and Departments of Surgery and Medicine, UCLA School of Medicine, Los Angeles, Calif. (A.W.A., S.M., and J.W.); Department of Physiology, Creighton University, Omaha, Neb. (TEA.); Department of Medicine, Tulane University, New Orleans, La. (D.C.); and Department of Surgery, Baylor College of Medicine, Houston, ‘Ikx. (F.C.B.). Supported by National Institutes of Health grant lR29DK46441-01 and the Hart and Louise Lyon Foundation. Presented at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, Calif., May 19-22,1996. Reprint requests: E Charles Brunicardi, M.D., Department of Surgery, Baylor College ofMedicine, One Baylor Plaza, Houston, TX 77030.
PY - 1997
Y1 - 1997
N2 - It is our hypothesis that intraislet somatostatin regulates beta cell secretion in the isolated perfused human pancreas. The present study was designed to determine the relative influence of intraislet somatostatin on the regulation of islet amyloid polypeptide (IAPP) and insulin secretion, and to determine the effect of specific somatostatin receptor (SSTR) agonists on beta cell secretion during immunoneutralization of endogenous somatostatin in the isolated perfused human pancreas. Single-pass perfusion was performed in pancreata obtained from seven cadaveric organ donors using a modified Krebs medium with 3.9 mmol/L glucose. Sequential test periods were separated by basal periods and experiments were performed by infusion of any of the following: (1) somatostatin monoclonal antibody (S-Ab); (2) S-Ab + SSTR2 agonist (DC32-87); or (3) S-Ab + SSTR5 agonist (DC32-92). The changes in insulin and IAPP secretion from basal levels during each stimulation were calculated. Infusion of S-Ab resulted in a significant increase in insulin secretion (2033 ± 429 pmol/L; P <0.05) but not IAPP. In the presence of S-Ab, infusion of the SSTR2 agonist resulted in a significant inhibition of insulin secretion (-1128 ± 457 pmol/L; P <0.05) but not IAPP. In the presence of S-Ab, infusion of the SSTR5 agonist had no significant effect on insulin or IAPP secretion. We conclude that intraislet somatostatin inhibits insulin secretion via SSTR2, but not IAPP secretion, in the isolated perfused human pancreas model and that this effect occurs via SSTR2. These results also suggest that insulin and IAPP secretion are regulated by different mechanisms despite being co-localized to the beta cell.
AB - It is our hypothesis that intraislet somatostatin regulates beta cell secretion in the isolated perfused human pancreas. The present study was designed to determine the relative influence of intraislet somatostatin on the regulation of islet amyloid polypeptide (IAPP) and insulin secretion, and to determine the effect of specific somatostatin receptor (SSTR) agonists on beta cell secretion during immunoneutralization of endogenous somatostatin in the isolated perfused human pancreas. Single-pass perfusion was performed in pancreata obtained from seven cadaveric organ donors using a modified Krebs medium with 3.9 mmol/L glucose. Sequential test periods were separated by basal periods and experiments were performed by infusion of any of the following: (1) somatostatin monoclonal antibody (S-Ab); (2) S-Ab + SSTR2 agonist (DC32-87); or (3) S-Ab + SSTR5 agonist (DC32-92). The changes in insulin and IAPP secretion from basal levels during each stimulation were calculated. Infusion of S-Ab resulted in a significant increase in insulin secretion (2033 ± 429 pmol/L; P <0.05) but not IAPP. In the presence of S-Ab, infusion of the SSTR2 agonist resulted in a significant inhibition of insulin secretion (-1128 ± 457 pmol/L; P <0.05) but not IAPP. In the presence of S-Ab, infusion of the SSTR5 agonist had no significant effect on insulin or IAPP secretion. We conclude that intraislet somatostatin inhibits insulin secretion via SSTR2, but not IAPP secretion, in the isolated perfused human pancreas model and that this effect occurs via SSTR2. These results also suggest that insulin and IAPP secretion are regulated by different mechanisms despite being co-localized to the beta cell.
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U2 - 10.1016/S1091-255X(97)80117-5
DO - 10.1016/S1091-255X(97)80117-5
M3 - Article
C2 - 9834355
AN - SCOPUS:0347306075
SN - 1091-255X
VL - 1
SP - 251
EP - 256
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
IS - 3
ER -