Abstract
Immunohistochemical techniques were used to study the occurrence and distribution of insulin-like growth factor 1 (IGF-1) and IGF-2 in the pancreas of man, dog, and rat and their possible coexistence with insulin (INS), glucagon (GLUC), somatostatin (SOM) and pancreatic polypeptide (PP). All control experiments, including pre-absorption of the antisera with synthetic peptide hormones, indicated the specificity of the immunoreactions obtained. In all species investigated, IGF-2-immunoreactivity occurred exclusively in INS-immunoreactive cells as was found by the use of consecutive sections and double immunofluorescence on identical sections. In contrast, IGF-1-immunoreactivity co-existed with GLUC-immunoreactivity. In man, singular SOM-immunoreactive cells also contained IGF-1-immunoreactivity. Thus, IGF-1 and IGF-2 can be localized by means of immunohistochemistry in the mammalian pancreas, and can be shown to occur in different islet cell populations. It is presumed that IGF-1 derived from A-cells and/or D-cells acts on the B-cells in a paracrine manner. The co-existence of IGF-2-immunoreactivity and INS-immunoreactivity in the human, rat, and dog endocrine pancreas indicates that mammalian IGF-2 and INS genes are regulated simultaneously.
Similar content being viewed by others
References
Andersson I, Billig H, Fryklund L, Hansson H-A, Isaksson O, Isgaard J, Nilsson A, Rozell B, Skottner A, Stemme S (1986) Localisation of IGF-I in adult rats. Immunohistochemical studies. Acta Physiol Scand 126:311–312
Beck F, Samani NJ, Byrne S, Morgan K, Gebhard R, Brammar WJ (1988) Histochemical localization of IGF-I and IGF-II mRNA in the rat between birth and adulthood. Development 104:29–39
Bell GI, Gerhard DS, Fong MN, Sanchez-Pescador R, Rall LB (1985) Isolation of the human insulin-like growth factor genes: insulin-like growth factor II and insulin genes are contiguous. Proc Natl Acad Sci USA 82:6450–6454
Bryson JM, Tuch BE, Baxter RC (1989) Production of insulin-like growth factor-II by human fetal pancreas in culture. J Endocrinol 121:367–373
Daughaday WH, Rotwein P (1989) Insulin-like growth factor I and II. Peptide, messenger ribonucleic acid and gene structures, serum and tissue concentrations. Endocrinol Rev 10:68–90
Grube D, Jörns A (1991) The endocrine pancreas of glucagon and somatostatin-immunized rabbits. Cell Tissue Res 265:251–260
Guler HP, Schmid C, Zapf J, Froesch ER (1989) Effects of recombinant insulin-like growth factor I on insulin secretion and renal function in normal human subjects. Proc Natl Acad Sci USA 86:2868–2872
Han VKM, Hill DJ, Strain AJ, Towle AC, Lauder JM, Underwood LE, D'Ercole AJ (1987) Identification of somatomedin/insulin-like growth factor immunoreactive cells in the human fetus. Pediatr Res 22:245–249
Hansson H-A, Edwall D, Löwenadler B, Norstedt G, Paleus S, Skottner A (1988a) Insulin-like growth factor I in the pancreas of normal and diabetic adult rats. Acta Physiol Scand 132:569–576
Hansson H-A, Nilsson A, Isgaard J, Billig H, Isaksson O, Skottner A, Andersson IK, Rozell B (1988b) Immunohistochemical localization of insulin-like growth factor I in the adult rat. Histochemistry 89:403–410
Hill DJ, Hogg J (1991) Growth factor control of pancreatic B cell hyperplasia. Bailliere's Clin Endocrinol Metabol 5:689–698
Höög A, Sandberg E, Efendic S, Östensson C-G, Grimelius L, Falkmer S (1991) Porcine diazepam-binding inhibitor is immunohistochemically colocalized with somatostatin in the D cells of human and porcine gastrointestinal tract and pancreatic islets. Endocr Pathol 2:161–165
Humbel RE (1990) Insulin-like growth factors I and II. Eur J Biochem 190:445–462
Leahy JL, Vandekerkhove KM (1990) Insulin-like growth factor-I at physiological concentrations is a potent inhibitor of insulin secretion. Endocrinology 126:1593–1598
Mathews LS, Norstedt G, Palmiter RD (1986) Regulation of insulin-like growth factor I gene expression by growth hormone. Proc Natl Acad Sci USA 83:9343–9347
Reinecke M (1981) Immunohistochemical localization of polypeptide hormones in endocrine cells of the digestive tract of Branchiostoma lanceolatum. Cell Tissue Res 219:445–456
Reinecke M, Drakenberg K, Falkmer S, Sara VR (1991a) Presence of IGF-1-like peptides in the neuroendocrine system of the Atlantic hagfish, Myxine glutinosa (Cyclostomata): evidence derived by chromatography, radioimmunoassay and immunohistochemistry. Histochemistry 96:191–196
Reinecke M, Höög A, Östenson CG, Efendic S, Grimelius L, Falkmer S (1991b) Phylogenetic aspects of pancreastatin-and chromogranin-like cells in the gastro-entero-pancreatic neuroendocrine system of vertebrates. Gen Comp Endocrinol 83:167–182
Reinecke M, Drakenberg K, Falkmer S, Sara VR (1992) Peptides related to insulin-like growth factor 1 in the gastro-entero-pancreatic system of bony and cartilaginous fish. Regul Pept 37:155–165
Romanus JA, Rabinovitch A, Rechler MW (1985) Neonatal rat islet cell cultures synthesize insulin-like growth factor I. Diabetes 34:696–702
Sara VR, Hall K (1990) The insulin-like growth factors and their binding proteins. Physiol Rev 70:591–614
Van Schravendijk CFH, Foriers A, Van den Brande JL, Pipeleers DG (1987) Evidence for the presence of type 1 insulin-like growth factor receptors on rat panceatic A and B cells. Endocrinology 121:1784–1788
Van Schravendijk CFH, Heylen L, Van den Brande JL, Pipeleers DG (1990) Direct effect of insulin and insulin-like growth factor on the secretory activity of rat pancreatic beta cells. Diabetologica 33:649–653
Zapf J, Walter H, Froesch ER (1981) Radioimmunological determination of insulinlike growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. J Clin Invest 68:1321–1330
Zenobi PD, Graf S, Ursprung H, Froesch ER (1992) Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion. J Clin Invest 89:1908–1913
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Maake, C., Reinecke, M. Immunohistochemical localization of insulin-like growth factor 1 and 2 in the endocrine pancreas of rat, dog, and man, and their coexistence with classical islet hormones. Cell Tissue Res 273, 249–259 (1993). https://doi.org/10.1007/BF00312826
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00312826