Summary
It was previously demonstrated that the two chemically related peptides calcitonin gene-related peptide (CGRP) and islet amyloid polypeptide (IAPP) both occur in the pancreas. We have now examined the cellular localization of CGRP and IAPP in the rat and the mouse pancreas. We found, in both the rat and the mouse pancreas, CGRP-immunoreactive nerve fibers throughout the parenchyma, including the islets, with particular association with blood vessels. CGRP-immunoreactive nerve fibers were regularly seen within the islets. In contrast, no IAPP-immunoreactive nerve fibers were demonstrated in this location. Furthermore, in rat islets, CGRP immunoreactivity was demonstrated in peripherally located cells, constituting a major subpopulation of the somatostatin cells. Such cells were lacking in the mouse islets. IAPP-like immunoreactivity was demonstrated in rat and mouse islet insulin cells, and, in the rat, also in a few non-insulin cells in the islet periphery. These cells seemed to be identical with somatostatin/CGRP-immunoreactive elements. In summary, the study shows (1) that CGRP, but not IAPP, is a pancreati neuropeptide both in the mouse and the rat; (2) that a subpopulation of rat somatostatin cells contain CGRP; (3) that mouse islet endocrine cells do not contain CGRP; (4) that insulin cells in both the rat and the mouse contain IAPP; and (5) that in the rat, a non-insulin cell population apparently composed of somatostatin cells stores immunoreactive IAPP. We conclude that CGRP is a pancreatic neuropeptide and IAPP is an islet endocrine peptide in both the rat and the mouse, whereas CGRP is an islet endocrine peptide in the rat.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahrén B, Pettersson M (1990) Calcitonin gene-related peptide (CGRP) and amylin and the endocrine pancreas. Int J Pancreatol 6:1–15
Ahrén B, Mårtensson H, Nobin A (1987) Effects of calcitonin gene-related peptide (CGRP) on islet hormone secretion in the pig. Diabetologia 30:354–359
Ahrén B, Lindskog S, Tatemoto K, Efendic S (1988) Pancreastatin inhibits insulin secretion and stimulates glucagon secretion in mice. Diabetes 37:281–285
Ahrén B, Mårtensson H, Ekman R (1989) Pancreatic nerve stimulation releases neuropeptide Y- but not galanin- or calcitonin gene-related peptide-like immunoreactivity from the pig pancreas. J Autonom Nerv Syst 27:11–16
Ahrén B, Östenson CG, Efendic S (1991a) Other islet peptides. In: Samols E (ed) The endocrine pancreas. Raven Press, New York, pp 153–173
Ahrén B, Berggren PO, Rorsman P, Östenson CG, Efendic S (1991b) Neuropeptides in the regulation of islet hormone secretion-localization, effects and mode of action. In: Vranic M, Efendic S, Hollenberg CM (eds) Fuel homeostasis and the nervous system. Plenum Press, New York, pp 129–142
Ar'Rajab A, Ahrén B (1991) Effects of amidated rat islet amyloid polypeptide on glucose-stimulated insulin secretion in vivo and in vitro in rats. Eur J Pharmacol 192:443–445
Börglum Jensen T, Fahrenkrug J, Sundler F (1991) Immunocytochemical localization of pancreastatin and chromogranin A in porcine neuroendocrine tissues. Regul Pept 36:283–297
Bretherton-Watt D, Ghatei MA, Bloom SR, Jamal H, Ferrier GJM, Girgis SI, Legon S (1989) Altered islet amyloid polypeptide (amylin) gene expression in rat models of diabetes. Diabetologia 32:881–883
Bretherton-Watt D, Gilbey SG, Ghatei MA, Beacham J, Bloom SR (1990) Failure to establish islet amyloid polypeptide (amylin) as a circulating beta cell inhibiting hormone in man. Diabetologia 33:115–117
Clark A, Edwards CA, Ostle LR, Sutton R, Rothbard JB, Morris JF, Turner RC (1989) Localization of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells and in islets of type-2 diabetic subjects. Cell Tissue Res 257:179–185
Coons AH, Leduc EM, Conolly JM (1955) Studies on antibody production. I. A method for the histochemical demonstration of specific antibodies and its application to a study of the hyperimmune rabbit. J Exp Med 102:49–60
Fujimura M, Greeley GH Jr, Hancock MB, Alwmark A, Santos A, Cooper CW, Reumont KJ, Ishizuka J, Thompson JC (1988) Colocalization of calcitonin gene-related peptide and somatostatin in pancreatic islet cells and inhibition of insulin secretion by calcitionin gene-related peptide in the rat. Pancreas 3:49–52
Hermansen K, Ahrén B (1990) Dual effects of calcitonin gene-related peptide on insulin secretion in the perfused dog pancreas. Regul Pept 27:149–157
Johnson KH, O'Brien TD, Westermark P (1991) Newly identified pancreatic protein islet amyloid polypeptide. What is its relationship to diabetes? Diabetes 40:310–314
Kahn SE, D'Alessio DA, Schwartz MW, Fujimoto WY, Ensinck JW, Taborsky GJ Jr, Porte D Jr (1990) Evidence of cosecretion of islet amyloid polypeptide and insulin by β-cells. Diabetes 39:634–638
Karlsson S, Sundler F, Ahrén B (1992) Neonatal capsaicin-treatment in mice: effects on pancreatic peptidergic nerves and 2-deoxy-D-glucose-induced insulin and glucagon secretion. J Autonom Nerv Syst (in press)
Ludvik B, Lell B, Hartter E, Schnack C, Prager R (1991) Decrease of stimulated amylin release precedes impairment of insulin secretion in type II diabetes. Diabetes 40:1615–1619
Lukinius A, Wilander E, Westermark GT, Engström U, Westermark P (1989) Co-localization of islet amyloid polypeptide and insulin in the B cell secretory granules of the human pancreatic islets. Diabetologia 32:240–244
Nagamatsu S, Carroll RJ, Grodsky GM, Steiner DF (1990) Lack of islet amyloid polypeptide regulation of insulin biosynthesis or secretion in normal rat islets. Diabetes 39:871–874
O'Brien TD, Westermark P, Johnson KH (1990) Islet amyloid polypeptide (IAPP) does not inhibit glucose-stimulated insulin secretion from isolated perfused rat pancreas. Biochem Biophys Res Commun 170:1223–1228
O'Brien TD, Westermark P, Johnson KH (1991) Islet amyloid polypeptide and insulin secretion from isolated perfused pancreas of fed, fasted, glucose-treated, and dexamethasone-treated rats. Diabetes 40:1701–1706
Ogawa A, Harris V, McCorkle SK, Unger RH, Luskey KL (1990) Amylin secretion from the rat pancreas and its selective loss after streptozotocin treatment. J Clin Invest 85:973–976
Ohsawa H, Kanatsuka A, Yamaguchi T, Makino H, Yoshida S (1989) Islet amyloid polypeptide inhibits glucose-stimulated insulin secretion from isolated rat pancreas islets. Biochem Biophys Res Commun 160:961–967
Pettersson M, Ahrén B (1988) Insulin and glucagon secretion in rats: effects of calcitonin gene-related peptide. Regul Pept 23:37–50
Pettersson M, Ahrén B (1990) Failure of islet amyloid polypeptide to inhibit basal and glucose-stimulated insulin secretion in model experiments in mice and rats. Acta Physiol Scand 138:389–394
Pettersson M, Ahrén B, Böttcher G, Sundler F (1986) Calcitonin gene-related peptide: occurrence in pancreatic islets in the mouse and the rat and inhibition of insulin secretion in the mouse. Endocrinology 119:865–869
Pettersson M, Lundquist I, Ahrén B (1987) Neuropeptide Y and calcitonin gene-related peptide: effects on glucagon and insulin secretion in the mouse. Endocr Res 13:407–417
Ravazzola M, Efendic S, Östenson CG, Tatemoto K, Hutton JC, Orci L (1988) Localization of pancreastatin immunoreactivity in porcine endocrine cells. Endocrinology 123:227–229
Rosenfeld MG, Mermod JJ, Amara SG, Swanson LWQ, Sawchenko PE, Rivier J, Vale WW, Evans RM (1983) Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 304:865–869
Steiner DF, Ohagi S, Nagamatsu S, Bell GI, Nishi M (1991) Is islet amyloid polypeptide a significant factor in pathogenesis or pathophysiology of diabetes? Diabetes 40:305–309
Sternini C, Brecha N (1986) Immunocytochemical identification of islet cells and nerve fibers containing calcitonin gene-related peptide-like immunoreactivity in the rat pancreas. Gastroenterology 90:1155–1163
Sternini C, Card JP (1991) Ultrastructural characterization of calcitonin gene-related peptide-containing fibers and islet cells in the rat pancreas. Pancreas 6:375–384
Su HC, Bishop AE, Power RF, Hamada Y, Polak JM (1987) Dual intrinsic and extrinsic origins of CGRP- and NPY-immunoreactive nerves of rat gut and pancreas. J Neurosci 7:2674–2687
Sundler F, Böttcher G (1991) Islet innervation with special reference to neuropeptides. In: Samols E (ed) The endocrine pancreas. Raven Press, New York, pp 29–52
Toshimori H, Narita R, Nakazoto M, Asai J, Mistukawa T, Kangawa K, Matsuo H, Matsukura S (1990) Islet amyloid polypeptide (IAPP) in the gastrointestinal tract and pancreas of man and rat. Cell Tissue Res 262:401–406
Tramu G, Pillez A, Leonardelli J (1978) An efficient method of antibody elution for the successive or simultaneous location of two antigens by immunocytochemistry. J Histochem Cytochem 26:322–324
Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien TD, Johnson K (1987) Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a novel neuropeptide-like protein also present in normal islet cells. Proc Natl Acad Sci USA 84:3881–3885
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ahrén, B., Sundler, F. Localization of calcitonin gene-related peptide and islet amyloid polypeptide in the rat and mouse pancreas. Cell Tissue Res 269, 315–322 (1992). https://doi.org/10.1007/BF00319623
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00319623