Summary
Amyloid deposition is a common pathological feature in insulinoma and in the islets of the pancreas in type-2 diabetic patients. The present immunohisto-chemical study revealed that normal B-cells, insulinoma, and amyloid deposits in insulinoma and diabetic pancreatic islets were commonly immunoreactive with antiserum to C-terminal synthetic tetradecapeptide of human islet amyloid polypeptide (IAPP) (24–37). Amyloid fibrils in insulinoma were also positive to IAPP by immunoelectron microscopy. A high level of IAPP was detected in the plasma and tissue of a insulinoma patient by radioimmunoassay suggesting that amyloid deposition in insulinoma is due to overproduction of IAPP. Amyloid deposits immunoreactive to IAPP were also seen in all diabetic pancreatic islets, but in no non-diabetic islets. There was much amyloid deposition in the islets of severe diabetics, whose B-cells demonstrated decreased immunoreactivities for IAPP and insulin. The IAPP content of the pancreas was 649.0 and 847.7 pg/mg wet weight in each of two diabetic patients, and 1034.6 and 1447.7 pg/mg wet weight in two non-diabetic patients. The present study revealed that IAPP is a bioactive peptide secreted from islet B-cells and are amyloidogenic peptide concerned in diabetogenensis and/or the progression of type-2 diabetes mellitus.
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Asai J, Nakazato M, Miyazato M, Kangawa K, Matsuo H, Matsukura S (1990) Regional distribution and molecular forms of rat islet amyloid poplypeptide. Biochem Biophys Res Commun 169:788–795
Betsholtz C, Christmanson L, Engström U, Rorsman F, Jordan K, O'Brien TD, Murtaugh M, Johnson KH, Westermark P (1990) Structure of cat islet amyloid polypeptide and identification of amino acid residues of potential significance for islet amyloid formation. Diabetes 39:118–122
Clark A, Cooper GJS, Lewis CE, Morris JF, Willis AC, Reid KBM, Turner RC (1987) Islet amyloid formed from diabetes-associated peptide may be pathogenic in type 2 diabetes. Lancet II:231–234
Clark A, Wells CA, Buley ID, Cruickshank JK, Vanhegan RI, Matthews DR, Cooper GJS, Holman RR, Turner RC (1988) Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res 9:151–159
Clark A, Edwards CA, Ostle LR, Sutton LR, Rothbard JB, Morris JF, Turner RC (1989) Localization of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells in islets of type-2 diabetic subjects. Cell Tissue Res 257:179–185
Cooper GJS, Willis AC, Clark A, Turner RC, Sim RB, Reid KBM (1987) Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patient. Proc Natl Acad Sci USA 84:8628–8632
Cooper GJS, Leighton B, Dimitriadis GD, Parry-Billings M, Kowalchuk JM, Howland K, Rothbard JB, Willis AC, Reid KBM (1988) Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle. Proc Natl Acad Sci USA 85:7763–7766
Datta HK, Zaidi M, Wimalawansa SJ, Ghatei MA, Beecham JL, Bloom SR, MacIntyre I (1989) In vivo and in vitro effects of amylin and amylin-amide on calcium metabolim in the rat and rabbit. Biochem Biophys Res Commun 162:876–881
Johnson KH, O'Brien TD, Hayden DW, Jordan K, Gohbrial HKG, Mahoney WC, Westermark P (1988) Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. Am J Pathol 130:1–8
Johnson KH, O'Brien TD, Jordan K, Westermark P (1989) Impaired glucose tolerance is associated with increased islet amyloid polypeptide (IAPP) immunoreactivity in pancreatic beta cells. Am J Pathol 135:245–250
Kogire M, Chang JK, Thonpson JC, Greeley GH Jr (1989) Inhibitory action of diabetes-associated peptide and calcitonin gene-related peptide on insulin release. 71st Annual Meeting of the Endocrine Society (abstract) Williamus & Wilkins, Baltimore, p 55
Leighton B, Cooper GJS (1988) Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. Nature 335:632–635
Liu TH, Tseng HC, Zhu Y, Zhon SX, Chen J, Cui QC (1985) Insulinoma: an immunohistochemical and morphological analysis of 95 cases. Cancer 56:1420–1429
Lukinius A, Wilander E, Westermark GT, Engstrom 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
Maloy AL, Longnecker DS, Greenberg ER (1981) The relation of islet amyloid to the clinical type of diabetes. Hum Pathol 12:917–922
Mitsukawa M, Takemura J, Asai J, Nakazato M, Kangawa K, Matsuo H, Matsukura S (1990) Islet amyloid polypeptide response to glucose, insulin, and somatostatin analogue administration. Diabetes 39:639–642
Nakazato M, Asai J, Kangawa K, Matsukura S, Matsuo H (1989) Establishment of radioimmunoassay for human iselet amyloid polypeptide and tissue content and plasma concentration. Biochem Biophys Res Commun 162:876–881
Ohsawa H, Kanatsuka A, Yamaguchi T, Makino H, Yoshida S (1989) Islet amyloid polypeptide inhibits glucose-sitimulated insulin secretion from isolated rat pancreatic islets. Biochem Biophys Res Commun 160:961–967
Petterson 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
Sanke T, Bell GI, Sample C, Rubenstein AH, Steiner DF (1988) An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing. J Biol Chem 263:17243–17246
Sanke T, Nishi M, Bell GI, Shows TB, Steiner DF (1989) Exonintron organization of the human islet amyloid polypeptide/diabetes associated peptide/amylin gene. 71st Annual Meeting of the Endocrine Society (abstract) Williamus & Wilkins, Baltimore, p 95
Toshimori H, Toshimori K, Ohura C, Matsuo H, Matsukura S (1988) The distribution of atrial natriuretic polypeptide (ANP)-containing cells in the adult rat heart. Anat Embryol 177:477–484
Toshimori H, Narita R, Nakazato M, Asai J, Mitsukawa T, Kangawa K, Matsuo H, Matsukura S (1990) Islet amyloid polypeptide (IAPP) in the gastrointestinal tract and pancreas in man and rats. Cell Tissue Res 262:401–406
Westermark P, Wilander E (1978) The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitus. Diabetologia 15:417–421
Westermark P, Grimelius L, Porak JM, Larsson LI, Noorden SV, Wilander E, Pearse AGE (1977) Amyloid in polypeptide hormone-producing tumor. Lab Invest 37:212–215
Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien T, Johnson KH (1987 a) Amyloid fibrils in human insulinoma and islets of Langhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. Proc Natl Acad Sci USA 84:3881–3885
Westermark P, Wernstedt C, Wilander E, O'Brien T, Hayden DW, Johnson KH (1987 b) Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats contains a novel putative polypeptide hormone. Am J Pathol 127:414–417
Westermark P, Wilander E, Westermark GT, Johnson KH (1987c) Islet aymyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals. Diabetologia 30:887–892
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Toshimori, H., Narita, R., Nakazato, M. et al. Islet amyloid polypeptide in insulinoma and in the islets of the pancreas of non-diabetic and diabetic subjects. Vichows Archiv A Pathol Anat 418, 411–417 (1991). https://doi.org/10.1007/BF01605927
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DOI: https://doi.org/10.1007/BF01605927