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Diabetologia

, Volume 38, Issue 4, pp 395–402 | Cite as

Non-parallelism of islet amyloid polypeptide (amylin) and insulin gene expression in rat islets following dexamethasone treatment

  • H. Mulder
  • B. Ahrén
  • M. Stridsberg
  • F. Sundler
Originals

Summary

Islet amyloid polypeptide (IAPP), a novel islet hormone candidate, has been reported to be over-expressed relative to insulin in rats following dexamethasone treatment. In order to investigate the expression of IAPP and insulin following dexamethasone treatment of rats for 12 days, we applied in situ hybridization and immunocytochemistry, allowing us to evaluate islet changes in gene expression and morphology. Tissue concentrations of IAPP and insulin were measured by radioimmunoassay. A low dose of dexamethasone (0.2 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 249±13% and 150±24% of controls, respectively (p<0.001 and p<0.01). A high dose of dexamethasone (2.0 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 490±13% and 203±9% of controls, respectively (p<0.001 and p<0.001). The pancreatic concentration of IAPP increased more than that of insulin (p<0.05). Morphometric analysis revealed that dexamethasone treatment induced both hyperplasia and hypertrophy of insulin cells. Changes in the cellular localization of IAPP and insulin mRNA were not observed. Thus, we conclude that the increased level of IAPP mRNA is due to both an increase at the cellular level as well as hyperplasia/hypertrophy of insulin cells. In contrast, the increased level of insulin mRNA appears to be due to hyperplasia/hypertrophy of insulin cells, since insulin gene expression decreased at the cellular level (p<0.001 vs controls). These observations provide further evidence that IAPP and insulin gene expression are regulated in a non-parallel fashion, which may be relevant to the pathogenesis of non-insulin-dependent diabetes mellitus

Key words

Islet amyloid polypeptide amylin insulin dexamethasone rat pancreatic islets in situ hybridization gene expression mRNA 

Abbreviations

IAPP

islet amyloid polypeptide

NIDDM

non-insulin-dependent diabetes mellitus

ISH

in situ hybridization

SSC

saline sodium citrate

CGRP

calcitonin gene related peptide

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • H. Mulder
    • 1
  • B. Ahrén
    • 2
  • M. Stridsberg
    • 3
  • F. Sundler
    • 1
  1. 1.Department of Medical Cell ResearchUniversity of LundLundSweden
  2. 2.Department of Medicine, Malmö General HospitalUniversity of LundSweden
  3. 3.Department of Clinical ChemistryUniversity HospitalUppsalaSweden

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