Effect of cyclosporin treatment on metabolic and hormonal responses to mixed meal plus oral glucose in dogs with intrasplenic pancreatic islet autograft.
We evaluated the effect of immunosuppressive concentrations of cyclosporin A (CsA), given intramuscularly, on the levels of glucose, insulin, C-peptide, glucagon, pancreatic polypeptide (PP), lactate, alanine and beta-hydroxy-butyrate in a group of pancreatectomized mongrel dogs with intrasplenic islet autografts, given mixed meal and oral glucose, while on or off CsA therapy. In whole blood, HPLC-measured drug levels ranged from 412 to 803 ng/ml. Basal glucose and insulin concentrations did not differ significantly between non-pancreatectomized, control dogs and transplanted animals, whether on or off CsA. After the meal challenge, glucose levels were significantly higher in transplanted animals than in normal dogs, and no additional deleterious effect of CsA was observed. Similar insulin and C-peptide responses were found in animals either on or off CsA treatment. Fasting and post-meal concentrations of glucagon, PP and intermediate metabolites were not affected by the drug. These results suggest that intramuscular CsA, given at doses known to sustain islet allograft function, has no detrimental effect on the hormonal and metabolic responses to mixed meal and oral glucose in dogs with intrasplenic islet autografts.
Marchetti
P
P
Department of Surgery, Washington University School of Medicine, St. Louis, MO.
Kneteman
N M
NM
Swanson
C J
CJ
Olack
B J
BJ
Scharp
D W
DW
D020155:3-Hydroxybutyric Acid; D000409:Alanine / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D005947:Glucose / Q000008:administration & dosage*; D006885:Hydroxybutyrates / Q000097:blood; D007273:Injections, Intramuscular; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010187:Pancreatic Hormones / Q000097:blood*
D001786:Blood Glucose; D006885:Hydroxybutyrates; D010187:Pancreatic Hormones; D016572:Cyclosporine; D005947:Glucose; D000409:Alanine; D020155:3-Hydroxybutyric Acid