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Acta Diabetologica

Erschienen in:

01.12.2012 | Original Article

In vitro effects of mycophenolic acid on survival, function, and gene expression of pancreatic beta-cells

verfasst von: R. Gallo, M. Natale, F. Vendrame, U. Boggi, F. Filipponi, P. Marchetti, F. Laghi Pasini, F. Dotta

Erschienen in: Acta Diabetologica | Sonderheft 1/2012

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Abstract

Post-transplant diabetes mellitus represents an important complication of prolonged immunosuppressive treatment after solid organ transplantation. The immunosuppressive toxicity, responsible for a persistent impairment of glucose metabolism in pancreatic islet-transplanted patients, is mainly attributed to calcineurin inhibitors and steroids, while other immunosuppressive molecules (azathioprine and mycophenolic acid, MPA) are considered not to have a toxic effect. In the present study, in vitro effects of MPA have been investigated in mouse beta-cell lines (βTC-1 and βTC-6) and in purified human pancreatic islets. βTC-1, βTC-6, and human pancreatic islets were exposed to various concentrations of MPA for different times. Consequently, we evaluated the viability, the induction of apoptosis, the glucose-stimulated insulin secretion, and the expression of β-cell function genes (Isl1, Pax6, Glut-2, glucokinase) and apoptosis-related genes (Bax and Bcl2). βTC-1, βTC-6, and human islets treated, respectively, for 48 and 72 h with 15–30 nM MPA showed altered islet architecture, as compared with control cells. We observed for βTC-1 and βTC-6 almost 70% reduction in cell viability; three to sixfold induction of TUNEL/apoptotic-positive cells quantified by FACS analysis. A twofold increase in apoptotic cells was observed in human islets after MPA exposure associated with strong inhibition of glucose-stimulated insulin secretion. Furthermore, we showed significant down-regulation of gene expression of molecules involved in β-cell function and increase rate between Bax/Bcl2. Our data demonstrate that MPA has an in vitro diabetogenic effect interfering at multiple levels with survival and function of murine and human pancreatic β-cells.

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Titel: In vitro effects of mycophenolic acid on survival, function, and gene expression of pancreatic beta-cells
verfasst von: R. Gallo
M. Natale
F. Vendrame
U. Boggi
F. Filipponi
P. Marchetti
F. Laghi Pasini
F. Dotta
Publikationsdatum: 01.12.2012
Verlag: Springer Milan
Erschienen in: Acta Diabetologica / Ausgabe Sonderheft 1/2012
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-011-0368-8

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