Dissociation of amylin from insulin secretion in β-cells is mediated by changes in expression

M. W. Cluck, L. O. Murphy, J. A. Knezttic, T. E. Adrian

Research output: Contribution to journalArticlepeer-review


Amylin is a 37 amino acid hormone normally co-secreted with insulin. It is the major component of pancreatic amyloid which appears responsible for islet destruction in type H diabetics. Since amylin also inhibits insulin secretion in vivo and in vitro, it may contribute directly and indirectly to the development of diabetes. Overproduction of amylin is likely to result from a dissociation between amylin and insulin regulation. While several studies have suggested that amylin and insulin (hormone and mRNA) are regulated in parallel, we have evidence of divergence. INSI is a rat β-cell line derived from an insulinoma which retains physiological glucose responsiveness. INS-1 cells treated with isobutylmethylxanthine (IBMX, 100 μM), which increases intracellular cAMP levels, induced a 10-fold rise in amylin secretion, nearly double that of insulin. Quantitative multiplex RT-PCR was developed to simultaneously measure both amylin and insulin mRNA using known concentrations of competitive, synthetic cRNA. IBMX (100 μM) increased amylin mRNA by 118% while insulin mRNA increased only 34% at 24 hours (P<0.05, N=5). Gel shift experiments, using probes homologous to the amylin promoter, show that IBMX induces protein-DNA binding to a CAAT domain. Since amylin secretion and mRNA levels increase in conjunction with increased promoter binding and the insulin promoter lacks a functional CAAT box, distinct elements may regulate amylin and insulin transcription independently. Differential regulation between amylin and insulin may explain pancreatic amyloid formation and the pathophysiology of type If diabetes.

Original languageEnglish
Pages (from-to)A1386
JournalFASEB Journal
Issue number8
Publication statusPublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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