Skip to main content
SpringerLink
Log in

Islet amyloid polypeptide gene expression in the endocrine pancreas of the rat: a combined in situ hybridization and immunocytochemical study

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The expression of the islet amyloid polypeptide (IAPP) gene within the endocrine pancreas and its correlation with insular neuroendocrine peptide localization were investigated in the rat. In situ hybridization with a 35S-labelled IAPP-mRNA specific oligonucleotide probe was combined with immunocytochemistry. In situ hybridization alone showed strong autoradiographic labelling of the pancreatic islets. In situ hybridization combined with immunocytochemistry for IAPP, revealed labelling of the IAPP-immunoreactive cells. However, when in situ hybridization was combined with immunocytochemistry for proinsulin, we noted a lack of proinsulin immunoreactivity in some peripherally located autoradiographically labelled islet cells. Furthermore, combination of in situ hybridization and immunocytochemistry for somatostatin showed autoradiographic labelling of somatostatin cells to a varying degree. This was further confirmed by showing cellular co-localization of IAPP and somatostatin by immunocytochemical double staining. We conclude that IAPP is mainly synthesized in insulin cells. Additionally, a subpopulation of the somatostatin cells is capable of IAPP synthesis. This may account for the relatively small reduction in the content of IAPP-mRNA in islets compared to the marked reduction of insulin mRNA after streptozotocin-induced diabetes in rats as previously reported.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahrén B, Sundler F (1992) Localization of calcitonin gene-related peptide and islet amyloid polypeptide in the rat and mouse pancreas. Cell Tissue Res 269:315–322

    Google Scholar 

  • Amara SG, Evans RM, Rosenfeld MG (1984) Calcitonin/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites. Mol Cell Biol 4:2151–2160

    Google Scholar 

  • Asai J, Nakazato M, Miyazato M, Kangawa K, Matsuo H, Matsukura S (1990) Regional distribution and molecular forms of rat islet amyloid polypeptide. Biochem Biophys Res Commun 169:788–795

    Google Scholar 

  • Bhogal R, Smith DM, Bloom SR (1992) Investigation and characterization of binding sites for islet amyloid polypeptide in rat membranes. Endocrinology 130:906–913

    Google Scholar 

  • 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

    Google Scholar 

  • Bretherton-Watt D, Gilbey SG, Ghatei MA, Beacham J, Macrae AD, Bloom SR (1992) Very high concentrations of islet amyloid polypeptide are necessary to alter the insulin respone to intravenous glucose in man. J Clin Endocrinol Metab 74:1032–1035

    Google Scholar 

  • Broderick CL, Brooke GS, DiMarchi RD, Gold G (1991) Human and rat amylin have no effects on insulin secretion in isolated rat pancreatic islets. Biochem Biophys Res Commun 177:932–938

    Google Scholar 

  • Chance WT, Balasubramaniam A, Zhang FS, Wimalawansa SJ, Fischer JE (1991) Anorexia following the intrahypothalamic administration of amylin. Brain Res 539:352–354

    Google Scholar 

  • Chuang L-M, Wu H-P, Jou T-S, Tai T-Y, Lin BJ (1992) Inhibitory effect of islet amyloid polypeptide of glucose-induced proinsulin biosynthesis in rat insuloma cells. Pancreas 7:472–476

    Google Scholar 

  • 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 patients. Proc Natl Acad Sci USA 84:8628–8632

    Google Scholar 

  • Denijn M, De Weger RA, Van Mansfeld ADM, Unnik JAM van, Lips CJM (1992) Islet amyloid polypeptide (IAPP) is synthesized in the islets of Langerhans. Histochemistry 97:33–37

    Google Scholar 

  • de Vroede M, Foriers A, Van De Winkel M, Madsen O, Pipeleers D (1992) Presence of islet amyloid polypeptide in rat islet B and D cells determines parallelism and dissociation between rat pancreatic islet amyloid polypeptide and insulin content. Biochem Biophys Res Commun 182:886–893

    Google Scholar 

  • Frontoni S, Choi SB, Banduch D, Rossetti L (1991) In vivo insulin resistance induced by amylin primarily through inhibition of insulin-stimulated glycogen synthesis in skeletal muscle. Diabetes 40:568–573

    Google Scholar 

  • Gedulin B, Cooper GJS, Young AA (1991) Amylin secretion from the perfused pancreas: dissociation from insulin and abnormal elevation in insulin-resistant diabetic rats. Biochem Biophys Res Commun 180:782–789

    Google Scholar 

  • Inoue K, Hisatomi A, Umeda F, Nawata H (1992) Relative hypersecretion of amylin to insulin from rat pancreas after neonatal STZ treatment. Diabetes 41:723–727

    Google Scholar 

  • In't Veld PA, Zhang F, Madsen OD, Klöppel G (1992) Islet amyloid polypeptide immunoreactivity in the human fetal pancreas. Diabetologia 35:272–276

    Google Scholar 

  • Johnson KH, O'Brien TD, Hayden DW, Jordan K, Ghobrial 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

    Google Scholar 

  • Kanatsuka A, Makino H, Ohsawa H, Tokuyama Y, Yamaguchi T, Yoshida S, Adachi M (1989) Secretion of islet amyloid polypeptide in response to glucose. FEBS Lett 259:199–201

    Google Scholar 

  • Kogire M, Ishizuka J, Thompson JC, Greeley GH Jr (1991) Inhibitory action of islet amyloid polypeptide and calcitonin generelated peptide on release of insulin from the isolated perfused rat pancreas. Pancreas 6:459–463

    Google Scholar 

  • Leffert JD, Newgard CB, Okamoto H, Milburn JL, Luskey KL (1989) Rat amylin: cloning and tissue-specific expression in pancreatic islets. Proc Natl Acad Sci USA 86:3127–3130

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Luskey KL (1992) Possible links between amylin and diabetes. Diabetes Care 41:297–299

    Google Scholar 

  • Madsen OD, Nielsen JH, Michelsen B, Westermark P, Betsholtz C, Nishi M, Steiner D (1991) Islet amyloid polypeptide and insulin expression are controlled differently in primary and transformed islet cells. Mol Cell Endocrinol 5:143–148

    Google Scholar 

  • Miyazato M, Nakazato M, Shiomi K, Aburaya J, Toshimori H, Kangawa K, Matsuo H, Matsukura S (1991) Identification and characterization of islet amyloid polypeptide in mammalian gastrointestinal tract. Biochem Biophys Res Commun 181:293–300

    Google Scholar 

  • Mosselman S, Höppener JWM, Zandberg J, Mansfeld ADM van, Geurts van Kessel AHM, Lips CJM, Jansz HS (1988) Islet amyloid polypeptide: identification and chromosomal localization of the human gene. FEBS Lett 239:227–232

    Google Scholar 

  • 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

    Google Scholar 

  • Nakazato M, Asai J, Kangawa K, Matsukura S, Matsuo H (1989) Establishment of radioimmunoassay for human islet amyloid polypeptide and its tissue content and plasma concentration. Biochem Biophys Res Commun 164:394–399

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Sternini C, De Giorgio R, Anderson K, Watt PC, Brunicardi FC, Widdison AL, Wong H, Reber HA, Walsh JH, Go VLW (1992) Species differences in the immunoreactive patterns of calcitonin gene-related peptide in the pancreas. Cell Tissue Res 269:447–458

    Google Scholar 

  • Suzuki S, Murakami M, Abe S, Satoh Y, Shintani S, Ishizuka J, Suzuki K-i, Thompson JC, Toyota T (1992) The effects of amylin on insulin secretion from Rin m5F cells and glycogen synthesis and lipogenesis in rat primary cultured hepatocytes. Diabetes Res Clin Pract 15:77–84

    Google Scholar 

  • Tabata H, Hirayama J, Sowa R, Furuta H, Negoro T, Sanke T, Nanjo K (1992) Islet amyloid polypeptide (IAPP/amylin) causes insulin resistance in perfused rat hindlimb muscle. Diabetes Res Clin Pract 15:57–62

    Google Scholar 

  • Westermark P, Wernstedt C, Wilander E, Sletten K (1986) A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas. Biochem Biophys Res Commun 140:827–831

    Google Scholar 

  • Westermark P, Wilander E, Westermark GT, Johnson KH (1987) Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals. Diabetologia 30:887–892

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Cell Research, University of Lund, Biskopsgaten 5, S-22362, Lund, Sweden

    Hindrik Mulder, Ann-Christin Lindh & Frank Sundler

Authors
  1. Hindrik Mulder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ann-Christin Lindh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frank Sundler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mulder, H., Lindh, AC. & Sundler, F. Islet amyloid polypeptide gene expression in the endocrine pancreas of the rat: a combined in situ hybridization and immunocytochemical study. Cell Tissue Res 274, 467–474 (1993). https://doi.org/10.1007/BF00314543

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00314543

Key words

Search

Navigation