Impaired insulin release from islets isolated from manganese deficient rats

Carl L Keen, P. L. Baly, J. L. Ensunsa, M. H. Watson

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Manganese (Mn) deficiency can result in a diabetic-like glucose intolerance in rats, which is due in part to a reduction in insulin synthesis and release. In the present study, we investigated whether isolated islets could be used to investigate the mechanisms underlying Mn deficiency-induced alterations in insulin production. Sprague-Dawley rats were fed a diet containing either 0.5 u.g Mn/g (Mn-) or 45 Hg Mn/g (Mn+) for 3 to 6 months. In order to confirm an impaired glucose metabolism, rats were fasted overnight and then given a glucose challenge (300 mg/kg BW). Mn- rats had fasting blood glucose concentrations that were significantly higher than Mn+ rats; in addition, the Mn- rats displayed abnormal glucose tolerance curves. Whole pancreatic analysis revealed that insulin tissue concentrations and insulin mRNA levels were 90% and 50% lower, respectively, in Mn- rats than in Mn+ rats. Islets were isolated from Mn- and Mn+ rats and cultured in media with several secretagogues (glucose, arachidonic acid or tolbutamide), which affect insulin release at various points in the cascade. Insulin production was assessed by media insulin concentration after 5 and 45 min; the first time period reflecting release of preformed insulin and the second reflecting release of preformed and newly synthesized insulin. In all cases, insulin secretion was significantly lower from islets of Mn- rats than from Mn+ rats. Incubation of islets with 1 μM Mn did not restore normal insulin secretion to islets of Mn- rats in the time period studied. These data confirm previous reports of a regulatory role of Mn in insulin synthesis and release, and show that isolated islets can be used to study the mechanisms underlying the effect of Mn.

Original languageEnglish (US)
JournalFASEB Journal
Issue number3
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology


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