Summary
Peptide antibodies raised in rabbits are widely used in biology and medicine. During immunization of the animals, the respective antibodies may affect the endocrine cells physiologically responsible for the synthesis of peptides used as antigens. Since corresponding morphological data are still sparse, the rabbit endocrine pancreas was systematically investigated by light microscopy and immunocytochemistry after long-term immunization against glucagon and somatostatin. Both immunizations led to an increase in the number of islets (nesidioblastosis), to the development of giant islets (macronesia), and to changes in the relative proportions of the major types of endocrine cells or their hormonal content. The latter changes differed after either immunization: glucagon immunization resulted in hypertrophy and hyperplasia of glucagon cells and a decrease in their hormonal content; somatostatin immunization led to an increased proportion of somatostatin cells and a lowered hormonal content of insulin cells. The various alterations were expressed differently according to islet type; islets of the rabbit pancreas differ in size or angioarchitecture, and in the proportion and distribution of endocrine cells. The present findings point to autocrine or paracrine effects of the respective peptides. These effects, however, are obviously of differing significance in morphologically heterogeneous islets.
Similar content being viewed by others
References
Bani Sacchi T, Bani D, Biliotti G (1985) Nesidioblastosis and islet cell changes related to endogenous hypergastrinemia. Virchows Arch [B] 48:261–276
Beischer W, Keller L, Maas M, Schiefer E, Pfeiffer EF (1976) Human C-peptide. Part I. Radioimmunoassay. Klin Wochenschr 54:709–715
Creutzfeldt W (1985) Endocrine tumors of the pancreas. In: Volk BW, Arquilla EW (eds) The diabetic pancreas, Plenum, New York London, pp 543–586
Cruickshank AH (1986) Pathology of the pancreas. Springer, Berlin Heidelberg
Ehrhart M, Jörns A, Grube D, Gratzl M (1988) Cellular distribution and amount of chromogranin A in bovine endocrine pancreas. J Histochem Cytochem 36:467–472
Epple A, Brinn JE (1987) The comparative physiology of the pancreatic islets. Springer, Berlin Heidelberg New York
Etzrodt H, Rosenthal J, Schröder KE, Pfeiffer EF (1983) Radioimmunoassay of somatostatin in human plasma. Clin Chim Acta 133:241–251
Ferner H (1952) Das Inselsystem des Pankreas. Thieme, Stuttgart
Feyrter F (1953) Über die peripheren endokrinen (parakrinen) Drüsen des Menschen. Maudrich, Wien Düsseldorf
Flatt PR, Swanston-Flatt SK (1979) Rapid production of potent glucagon antisera in the guinea pig. Horm Metab Res 11:581–582
Freytag G (1981) Morphologic changes in pancreas islets after active or passive immunization against insulin. In: Keck K, Erb P (eds) Basic and clinical aspects of immunity to insulin. de Gruyter, Berlin New York, pp 285–302
Fuchs U, Hahn von Dorsche H, Ziegler M (1984) Glucagon antibodies alter Langerhans' islets. Biomed Biochim Acta 43:691–693
Fujita T (1983) Messenger substances of neurons and paraneurons: their chemical nature and the routes and ranges of their transport to targets. Biomed Res 4:239–256
Fujita T, Kanno T, Kobayashi S (1988) The paraneuron. Springer, Tokyo Berlin Heidelberg
Grey N, McGuigan JE, Kipnis DM (1979) Neutralization of endogenous glucagon by high titer glucagon antiserum. Endocrinology 86:1383–1388
Grube D (1986) The endocrine cells of the digestive system: amines, peptides, and modes of action. Anat Embryol 175:151–162
Grube D, Kusumoto Y (1986) Serial semithin sections in immunohistochemistry: techniques and applications. Arch Histol Jpn 49:391–410
Haas A (1984) Das endokrine Pankreas von Kaninchen nach Langzeitimmunisierung mit Glukagon. Med Thesis, Universität Ulm, FRG
Hahn von Dorsche H, Ziegler M (1981) A-cell-hyperplasia of islets of Langerhans of rabbits after immunisation with glucagon. Acta Histochem (Jena) 68:290–293
Holst JJ, Galbo H, Richter EA (1978) Neutralization of glucagon by anti-serum as a tool in glucagon physiology. Lack of depression of basal glucose after antiserum treatment in rats. J Clin Invest 62:182–190
Honey RN, Arimura A, Weir GC (1981) Somatostatin neutralization stimulates glucagon and insulin secretion from avian pancreas. Endocrinology 109:1971–1974
In't Veld PA (1988) Insulin release and islet cell junctions In: Lefébvre PJ, Pipeleers DG (eds) The pathology of the endocrine pancreas in diabetes. Springer, Berlin Heidelberg New York, pp 233–248
Jörns A, Grube D (1991) The endocrine pancreas of glucagon-and somatostatin-immunized rabbits. II. Electron microscopy. Cell Tissue Res 265:261–273
Jörns A, Deterding E, Grube D (1986) Effects of glucagon immunization on the rabbit endocrine pancreas. Acta Endocrinol [Suppl 274] (Copenh):128–129
Jörns A, Barklage E, Grube D (1988) Heterogeneities of the islets in the rabbit pancreas and the problem of “paracrine” regulation of islet cells. Anat Embryol 178:297–307
Jonas L, Putzke HP, Hahn von Dorsche H (1983) Islands of Langerhans of rats (Rattus norvegicus forma alba) after high prednisolon-dosage. A semiquantitative light and electron microscopic study. Anat Anz 154:273–282
Klöppel G (1977) Die funktionelle Pathomorphologie der B-Zellen des Inselsystems. Prog Pathol 108:1–106
Klöppel G, Heitz PhU (eds) (1984) Pancreatic pathology. Churchill Livingstone, Edinburgh London Melbourne
Klöppel G, Altenähr E, Freytag G (1972) Studies on ultrastructure and immunology of the insulitis in rabbits immunized with insulin. Virchows Arch [A] 356:1–15
Lasaga M, Debeljuk L, Afione S, Aleman IT, Duvilanski B (1989) Effects of a passive immunization against vasoactive intestinal peptide on serum prolactin and LH levels. Neuroendocrinology 49:574–579
Lecompte PM, Steinke J, Soeldner JS, Renold AE (1966) Changes in the islets of Langerhans in cows injected with heterologous and homologous insulin. Diabetes 15:586–596
Logothetopoulos J, Bell EG (1966) Histogical and autoradiographic studies of the islets of mice injected with insulin antibody. Diabetes 15:205–211
Nieschlag E, Herrmann J, Usadel KH, Schwedes U, Schöffling K, Krüskemper HL (1973a) Thyroid hypertrophy and hyperfunction caused by active immunization with thyroid hormones. J Endocrinol 57:555–556
Nieschlag E, Usadel KH, Schwedes U, Kley HK, Schöffling K, Krüskemper HL (1973b) Alterations in testicular morphology and function in rabbits following active immunization with testosteron. Endocrinology 92:1142–1147
Nishino T, Shima K, Shimura Y, Tanaka R, Kodaira T, Imagawa K, Kumahara Y (1980) A study of the physiological role of glucagon. Passive immunization with antiserum specific for pancreactic glucagon in rats. Endocrinol Jpn 1:109–113
Östenson CG, Swenn I, Flatt PR, Berggren PO (1982) Insulin antibody production in guinea pigs is accompanied by disturbances in pancreatic islets morphology and glucagon secretion. Diabete Metab 8:241–247
Orci L (1984) Patterns of cellular and subcellular organization in the endocrine pancreas. The Sir Henry Dale lecture for 1983. J Endocrinol 102:3–11
Orci L, Unger RH (1975) Functional subdivision of islets of Langerhans and possible role of D-cells. Lancet II:1243–1244
Patel YC, Pierzchala I, Amherdt M, Orci L (1985) Effects of cysteamine and antibody to somatostatin on islet cell function in vitro. Evidence that intracellular somatostatin deficiency augments insulin and glucagon secretion. J Clin Invest 75:1249–1255
Pipeleers D (1987) The biosociology of pancreatic B cells. Diabetologia 30:277–291
Pipeleers D, In't Veld P, Maes E, Van de Winkel M (1982) Glucose-induced insulin release depends on functional cooperation between islet cells. Proc Natl Acad Sci USA 79:7322–7325
Samols E, Bonner-Weir S, Weir GC (1986) Intra-islet insulin-glucagon-somatostatin relationships. Clin Endocrinol Metab 125:33–58
Sofroniew MV, Madler M, Müller OA, Scriba PC (1978) A method for the consistent production of high quality antisera to small peptide hormones. Fresenius Zschr Anal Chem 290:163
Stefan Y, Meda P, Neufeld M, Orci L (1987) Stimulation of insulin secretion reveals heterogeneity of pancreatic B cells in vivo. J Clin Invest 80:175–183
Sternberger LA (1986) Immunocytochemistry, 3rd edn. Wiley, New York
Tan K, Tsiolakis D, Marks V (1985a) Effect of glucagon antibodies on plasma glucose, insulin and somatostatin in the fasting and fed rat. Diabetologia 28:435–440
Tan K, Atabani G, Marks V (1985b) Divergent effect of glucagon antibodies on arginine and glucose-stimulated insulin secretion in the rat. Diabetologia 28:441–444
Taugner R, Hackenthal E, Inagami T, Nobiling R, Poulsen K (1982) Vascular and tubular renin in the kidneys of mice. Histochemistry 75:473–484
Tröger M, Jörns A, Grube D (1989) Morpho-functional heterogeneity of mammalian insulin cells. Acta Endocrinol [Suppl 1] (Copenh):18–19
Usadel KH, Rausch B, Schwedes U, Beyer J, Happ J (1975) Active immunization with glucagon, effect on the endocrine pancreas. Acta Endocrinol [Suppl 193] (Copenh):40
Weir GC, Bonner-Weir S (1990) Islets of Langerhans: the puzzle of intra-islet interactions and their relevance to diabetes. J Clin Invest 85:983–987
Author information
Authors and Affiliations
Additional information
Dedicated to Professor Dr. Tsuneo Fujita, Niigata University, Japan
Rights and permissions
About this article
Cite this article
Grube, D., Jörns, A. The endocrine pancreas of glucagon-and somatostatin-immunized rabbits. Cell Tissue Res. 265, 251–260 (1991). https://doi.org/10.1007/BF00398073
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00398073