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Am J Physiol Endocrinol Metab 276: E19-E24, 1999;
0193-1849/99 $5.00
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Vol. 276, Issue 1, E19-E24, January 1999

Islet amyloid polypeptide tonally inhibits beta -, alpha -, and delta -cell secretion in isolated rat pancreatic islets

Feng Wang1, Thomas E. Adrian3, Gunilla T. Westermark2, Xianzhong Ding3, Thomas Gasslander2, and Johan Permert1

1 Department of Surgery, Karolinska Institute at Huddinge University Hospital, Huddinge 14186; 2 Department of Biomedicine and Surgery, Linköping University Hospital, Linköping 58185, Sweden; and 3 Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178

Islet amyloid polypeptide (IAPP, or amylin) is produced in pancreatic beta -cells. The intraislet significance of IAPP is still uncertain. In the present study, paracrine effects of endogenous IAPP and somatostatin were investigated in isolated rat pancreatic islets. The intraislet IAPP activity was inhibited with an IAPP antiserum or a specific antagonist [IAPP-(8---37)]. Somatostatin activity was inhibited by immunoneutralization. Basal insulin and glucagon secretion were not affected by the somatostatin and/or IAPP blockade. Arginine-stimulated insulin and glucagon secretion were dose dependently increased by IAPP antiserum, IAPP-(8---37), and somatostatin antiserum, respectively. Arginine-stimulated somatostatin secretion was dose dependently potentiated by IAPP antiserum. Insulin secretion induced by 16.7 mM glucose was enhanced by IAPP antiserum and IAPP-(8---37), respectively. A combination of somatostatin antiserum with IAPP antiserum or IAPP-(8---37) further enhanced the arginine-stimulated insulin and glucagon secretion compared with effects when the blocking reagents were used individually. These results indicate that endogenously produced IAPP tonally inhibits stimulated insulin, glucagon, and somatostatin secretion. Furthermore, the paracrine effects of IAPP and somatostatin are additive.

amylin; somatostatin; insulin; glucagon


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