The effects of repeated exposure to sub-toxic doses of plecomacrolide antibiotics on the endocrine pancreas

Kalindi D. Hettiarachchi, Paul Z. Zimmet, Mark A. Myers

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The plecomacrolide vacuolar ATPase inhibitors bafilomycin and concanamycin contaminate tuberous vegetables and damage pancreatic islets in mice. The consequences of repeated exposure of adult mice to sub-toxic doses of bafilomycin A1 or concanamycin A was examined by injection of the plecomacrolides on each of five consecutive days. There was a significant reduction in islet size in female C57BL/6j mice (p < 0.004 and p < 0.0001 respectively). There were no significant differences in fasted insulin levels and β cell mass between treated and control groups but oral glucose tolerance worsened with increasing age in BALB/c female mice injected with concanamycin A. Streptozotocin reduced glucose tolerance and islet number but not islet size in all strains and sexes. Chronic exposure of C57BL/6j mice to concanamycin A for 16 weeks caused a significant reduction in islet size in both sexes and a significant increase in the spleen weight of female mice (p < 0.001). We conclude that repeated exposure to small quantities of vacuolar proton-translocating ATPase inhibitory plecomacrolides reduces islet size and can lead to glucose intolerance, possibly due to impaired maintenance of pancreatic islets. This may lead to earlier progression to β cell failure and insulin deficiency in those at risk of diabetes.

LanguageEnglish
Pages1966-1977
Number of pages12
JournalFood and Chemical Toxicology
Volume44
Issue number12
DOIs
Publication statusPublished - Dec 2006
Externally publishedYes

Keywords

  • Diabetes
  • Pancreatic islet
  • Plecomacrolide
  • Proton translocating ATPase
  • Toxin

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Hettiarachchi, Kalindi D. ; Zimmet, Paul Z. ; Myers, Mark A. / The effects of repeated exposure to sub-toxic doses of plecomacrolide antibiotics on the endocrine pancreas. In: Food and Chemical Toxicology. 2006 ; Vol. 44, No. 12. pp. 1966-1977.
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The effects of repeated exposure to sub-toxic doses of plecomacrolide antibiotics on the endocrine pancreas. / Hettiarachchi, Kalindi D.; Zimmet, Paul Z.; Myers, Mark A.

In: Food and Chemical Toxicology, Vol. 44, No. 12, 12.2006, p. 1966-1977.

Research output: Contribution to journalArticle

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