Improved human islet preparations using glucocorticoid and exendin-4

Atsushi Miki, Camillo Ricordi, Toshiyuki Yamamoto, Yasunaru Sakuma, Ryosuke Misawa, Atsuyoshi Mita, Luca A Inverardi, Rodolfo Alejandro, Hirohito Ichii

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1317-1322
Number of pages6
JournalPancreas
Volume43
Issue number8
StatePublished - Jan 1 2014

Fingerprint

Methylprednisolone
Glucocorticoids
Islets of Langerhans
Islets of Langerhans Transplantation
Chemokines
Insulin
Culture Media
Cell Survival
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Cell Transplantation
Phosphorylation
Cytokines
exenatide
Glucose
Control Groups

Keywords

  • Culture
  • Cytokine
  • Glucagon-like peptide-1
  • Insulin secretion
  • Islet function
  • β-cell viability

ASJC Scopus subject areas

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Miki, A., Ricordi, C., Yamamoto, T., Sakuma, Y., Misawa, R., Mita, A., ... Ichii, H. (2014). Improved human islet preparations using glucocorticoid and exendin-4. Pancreas, 43(8), 1317-1322.

Improved human islet preparations using glucocorticoid and exendin-4. / Miki, Atsushi; Ricordi, Camillo; Yamamoto, Toshiyuki; Sakuma, Yasunaru; Misawa, Ryosuke; Mita, Atsuyoshi; Inverardi, Luca A; Alejandro, Rodolfo; Ichii, Hirohito.

In: Pancreas, Vol. 43, No. 8, 01.01.2014, p. 1317-1322.

Research output: Contribution to journalArticle

Miki, A, Ricordi, C, Yamamoto, T, Sakuma, Y, Misawa, R, Mita, A, Inverardi, LA, Alejandro, R & Ichii, H 2014, 'Improved human islet preparations using glucocorticoid and exendin-4', Pancreas, vol. 43, no. 8, pp. 1317-1322.
Miki A, Ricordi C, Yamamoto T, Sakuma Y, Misawa R, Mita A et al. Improved human islet preparations using glucocorticoid and exendin-4. Pancreas. 2014 Jan 1;43(8):1317-1322.
Miki, Atsushi ; Ricordi, Camillo ; Yamamoto, Toshiyuki ; Sakuma, Yasunaru ; Misawa, Ryosuke ; Mita, Atsuyoshi ; Inverardi, Luca A ; Alejandro, Rodolfo ; Ichii, Hirohito. / Improved human islet preparations using glucocorticoid and exendin-4. In: Pancreas. 2014 ; Vol. 43, No. 8. pp. 1317-1322.
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abstract = "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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AU - Misawa, Ryosuke

AU - Mita, Atsuyoshi

AU - Inverardi, Luca A

AU - Alejandro, Rodolfo

AU - Ichii, Hirohito

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N2 - 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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