Effects of artemether on pancreatic islet morphology, islet cell turnover and alpha-cell transdifferentiation in insulin-deficient Glu(CreERT2);ROSA26-eYFP diabetic mice

Dipak Sarnobat, Ryan A Lafferty, R Charlotte Moffett, Andrei I Tarasov, Peter R Flatt, Nigel Irwin

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Abstract

The antimalarial drug artemether is suggested to effect pancreatic islet cell transdifferentiation, presumably through activation γ-aminobutyric acid receptors, but this biological action is contested. We have investigated changes in α-cell lineage in response to 10-days treatment with artemether (100 mg/kg oral, once daily) on a background of β-cell stress induced by multiple low-dose streptozotocin (STZ) injection in GluCreERT2; ROSA26-eYFP transgenic mice. Artemether intervention did not affect the actions of STZ on body weight, food and fluid intake or blood glucose. Circulating insulin and glucagon were reduced by STZ treatment, with a corresponding decline in pancreatic insulin content, which were not altered by artemether. The detrimental changes to pancreatic islet morphology induced by STZ were also evident in artemether-treated mice. Tracing of α-cell lineage, through co-staining for glucagon and yellow fluorescent protein (YFP), revealed a significant decrease of the proportion of glucagon+YFP- cells in STZ-diabetic mice, which was reversed by artemether. However, artemether had no effect on transdifferentiation of α-cells into β-cells and failed to augment the number of bi-hormonal, insulin+glucagon+, islet cells. Our observations confirm that artemisinin derivatives do not impart meaningful benefits on islet cell lineage transition events or pancreatic islet morphology. [Abstract copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.]
Original languageEnglish
Pages (from-to)rgac075
JournalJOURNAL OF PHARMACY AND PHARMACOLOGY
Early online date7 Oct 2022
DOIs
Publication statusPublished (in print/issue) - 7 Oct 2022

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.

Keywords

  • artemether
  • GABA
  • transdiferentiation
  • STZ-induced diabetes
  • lineage tracing

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