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Improved human islet preparations using glucocorticoid and exendin-4

  • Author(s): Miki, A
  • Ricordi, C
  • Yamamoto, T
  • Sakuma, Y
  • Misawa, R
  • Mita, A
  • Inverardi, L
  • Alejandro, R
  • Ichii, H
  • et al.
Abstract

Copyright © 2014 by Lippincott Williams & Wilkins. Objectives: The effects of glucocorticoid during culture on human islet cells have been controversial. Exendin-4 (EX) enhances the insulin secretion and significantly improves clinical outcomes in islet cell transplantation. In this study, we examined the effects of glucocorticoids and EX on human islet cells during pretransplant culture.Methods: Methylprednisolone (MP) and/or EX were added to the standard culture medium for clinical islet cell transplantation. Islets were cultured for 24 hours with 3 different conditions (control, no additives; MP alone; and MP + EX). β-Cell fractional viability, cellular composition, multiple cytokine/chemokine production, multiple phosphorylation proteins, and glucose-induced insulin secretion were evaluated.Results: Viable β-cell survival in MP and MP + EX group was significantly higher than in the control group. Exendin-4 prevented MP-induced reduction of insulin secretion. Methylprednisolone supplementation to the culture medium decreased cytokine and chemokine production. Moreover, extracellular signal-regulated kinase 1/2 phosphorylation was significantly increased by MP and MP + EX.Conclusions: Glucocorticoid supplementation into culture media significantly decreased the cytokine/chemokine production and increased the extracellular signal-regulated kinase 1/2 phosphorylation, resulting in the improvement of human β-cell survival. In addition, EX maintained the insulin secretion suppressed by MP. The supplementation of MP and EX together could be a useful strategy to create suitable human islets for transplantation.

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