Isolation and molecular characterization of porcine calcitonin gene-related peptide (CGRP) and its endocrine effects in the porcine pancreas

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T N Rasmussen, M Bersani, P Schmidt, L Thim, Hans Kofod, P N Jørgensen, S S Poulsen, J J Holst

The aim of this study was to investigate the possible role of porcine calcitonin gene-related peptide (CGRP) in the regulation of the endocrine porcine pancreas. Initially, we isolated and purified CGRP from extracts of porcine adrenal glands and pancreases. A single molecular form of the peptide was found in the two tissues. The adrenal peptide was sequenced and found to differ from human alpha-CGRP at six positions and from human beta-CGRP at three positions. By immunohistochemistry, CGRP was found in nerve fibers in the pancreatic ganglia. A synthetic replica of the porcine peptide was infused at different dose levels (10(-10), 10(-9), and 10(-8) M) into isolated perfused porcine pancreata. With 5 mmol/L glucose in the perfusate. CGRP at 10(-10) and 10(-9) M increased insulin and glucagon secretion, whereas significant decreases were observed with 10(-8) M. Somatostatin secretion was increased significantly by 10(-8) M CGRP. In immunoneutralization studies (n = 6) using a high-affinity somatostatin antibody, the inhibitory effect of CGRP at 10(-8) M was reversed to a significant stimulation of insulin and glucagon secretion. Insulin secretion in response to square-wave increases in glucose concentration to 11 mM was inhibited dose dependently by CGRP; at 10(-8) M the insulin output decreased by 72+/-9% (n = 6). The present results indicate that CGRP may be involved in the regulation of insulin and glucagon secretion from the porcine pancreas.
Original languageEnglish
Issue number2
Pages (from-to)195-204
Number of pages10
Publication statusPublished - Mar 1998

    Research areas

  • Adrenal Glands, Amino Acid Sequence, Animals, Antibodies, Calcitonin Gene-Related Peptide, Glucagon, Humans, Immunohistochemistry, Insulin, Islets of Langerhans, Molecular Sequence Data, Nerve Fibers, Pancreas, Sequence Homology, Somatostatin, Swine

ID: 204979