In vivo and in vitro effects of cyclosporin A on glucose transport by soleus muscles of mice.
The effect of cyclosporin A (CyA) on 2-deoxyglucose (2DG) uptake by soleus muscles of ICR mice was studied in vivo and in vitro. The basal and insulin-stimulated uptakes of 2DG by the muscles as well as the plasma insulin level were significantly decreased by the in vivo treatment of mice with 20 mg/kg/day of CyA for 6 weeks (P less than 0.01 and P less than 0.05), whereas the insulin binding was increased inversely in the muscles from 20 mg/kg/day CyA-treated mice. The insulin-stimulated uptake of 2DG by the muscles was significantly decreased by the in vitro treatment of the muscles with 1, 10 and 100 micrograms/mL of CyA (P less than 0.05 and P less than 0.01, respectively), while the basal uptake of 2DG was not changed by the in vitro treatment of the muscles with CyA. The insulin binding to the muscles was not altered by the in vitro treatment of the muscles with CyA. These findings suggest that CyA affects not only the insulin secretion from the pancreatic islets but also the postbinding mechanisms of insulin action on the glucose transport by the muscles, which may account for a part of the diabetogenic effect of CyA.
Ikeuchi
M
M
Department of Pediatrics, Ehime University School of Medicine, Japan.
Kida
K
K
Goto
Y
Y
Kaino
Y
Y
Matsuda
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism
D007328:Insulin; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D005947:Glucose