Is the cyclosporin A toxicity on rat pancreatic B-cells modulated by the MHC?
High Cyclosporin A doses (50 mg/kg b.w.) were given male Wistar rats either homozygous for RT1a or RT1u. Both rat strains are characterized by a similar diminished body weight gain. Cyclosporin A exerted in both strains an increased fed plasma glucose, decreased glucose tolerance and diminished pancreatic insulin content, however, the Wistar rat strain with the MHC RT1u was more sensitive to the effect of Cyclosporin A, indicated by a more marked alteration of pancreatic B-cells and a delayed recovery after drug withdrawal. We concluded that the MHC modulated either the Cyclosporin A metabolism (degradation) or the pancreatic B-cell sensitivity to toxic damage.
Hahn
H J
HJ
Central Institute of Diabetes G. Katsch, Karlsburg, GDR.
Laube
R
R
Klöting
I
I
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002470:Cell Survival / Q000187:drug effects; D003524:Cyclosporins / Q000633:toxicity*; D005947:Glucose / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000633:toxicity; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000032:analysis / Q000166:cytology / Q000187:drug effects*; D008285:Major Histocompatibility Complex; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D007328:Insulin; D005947:Glucose