Isolation and molecular characterization of porcine calcitonin gene-related peptide (CGRP) and its endocrine effects in the porcine pancreas
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Isolation and molecular characterization of porcine calcitonin gene-related peptide (CGRP) and its endocrine effects in the porcine pancreas. / Rasmussen, T N; Bersani, M; Schmidt, P; Thim, L; Kofod, Hans; Jørgensen, P N; Poulsen, S S; Holst, J J.
In: Pancreas, Vol. 16, No. 2, 03.1998, p. 195-204.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Isolation and molecular characterization of porcine calcitonin gene-related peptide (CGRP) and its endocrine effects in the porcine pancreas
AU - Rasmussen, T N
AU - Bersani, M
AU - Schmidt, P
AU - Thim, L
AU - Kofod, Hans
AU - Jørgensen, P N
AU - Poulsen, S S
AU - Holst, J J
PY - 1998/3
Y1 - 1998/3
N2 - 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.
AB - 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.
KW - Adrenal Glands
KW - Amino Acid Sequence
KW - Animals
KW - Antibodies
KW - Calcitonin Gene-Related Peptide
KW - Glucagon
KW - Humans
KW - Immunohistochemistry
KW - Insulin
KW - Islets of Langerhans
KW - Molecular Sequence Data
KW - Nerve Fibers
KW - Pancreas
KW - Sequence Homology
KW - Somatostatin
KW - Swine
M3 - Journal article
C2 - 9510144
VL - 16
SP - 195
EP - 204
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 2
ER -
ID: 204979