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

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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)S123-S131
JournalActa Diabetologica
Issue number1 SUPPL.
StatePublished - Dec 2012
Externally publishedYes


  • Beta-cells
  • Human islets
  • Immunosuppressive drugs
  • Mycophenolic acid

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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