Effects of cyclosporin a on the endocrine pancreas of the rat. Morphological and immunohistochemical studies

Abstract

Treatment with the immunosuppressive agent cyclosporin A frequently gives rise to functional alteration of the islets of Langerhans which may result in diabetes. Light microscopy, immunocytochemical, and electron microscopy investigations demonstrate degranulation, vacuolization, and destruction of endocrine pancreatic cells in treated animals. Similar changes, but of a milder degree, are observed in the A-cells. The morphological alterations described are likely to be the result of inhibition of synthesis and secretion in B-cells.

Alteration of Pancreatic B‐Cells in Wistar Rats Treated with Non‐Diabetogenic Doses of Cyclosporin A

“…The early recognition of toxic side effects of cyclosporin A, which is now widely used as an immunosuppressive drug in the treatment of either organ recipients or patients suffering from autoimmune diseases, has only been partially solved. Besides numerous effects on other non-lymphoid organs it is now well recognized that cyclosporin A exerts direct toxic effects on pancreatic B-cells (Merrell et al 1985;Hahn et al 1986;Yale et al 1985;Anderson et al 1984;Helmchen et al 1984;Nielsen et al 1986;Hahn et al 1986;Kojima et al 1986;Healey et al 1990;Eun et al 1987;Jablenska et al 1989;Papaccio & Esposito 1990;Bani-Sacchi et al 1990;Roth et al 1989;Hahn et al 1987;Bending et al 1987;Papaccio et al 1989;Hahn et al 1989), which can be observed in different species including human beings (Nielsen et al 1986;Roth et al 1989;Bending et al 1987). The cyclosporin A doses investigated in the experimental series described were too low to prevent allograft rejection (Hahn et al 1987(Hahn et al & 1989 or to alter kidney, liver or pancreas morphology (Laube 1989).…”

“…The latter observation could be a result of diminished pancreatic B-cell replication and/or regeneration (7-9) caused by CS-A, which inferes with the protein synthesis of pancreatic B-cells (Eun et al 1987). Cyclosporin A produced marked morphological changes in pancreatic B-cells, such as vacuolization, dilation of rough endoplasmatic reticulum cisternae and enlargment of the Golgi apparatus (Helmchen et al 1984;Healey et al 1990;Jablenska et al 1989; Bani-Sacchi et al 1990). Consequently the drug induces dosedependent impaired glucose tolerance and finally hyperglycaemia, i.e.…”