In vivo effect of FK506 on human pancreatic islets.
The purpose of this study was to evaluate the in vivo effect of FK506 on human pancreatic islets. Twenty-five nude mice were made diabetic by one intravenous injection of streptozotocin. Approximately 600 islets were administered in the renal subcapsular space 3-5 days following streptozotocin administration. One week after transplantation, the mice were divided in four groups. In group 1, the animals received 1 injection of 0.5 ml of diluent i.p. daily for one week. In groups 2, 3, and 4 the treatments were daily i.p. injection of 0.3, 1, and 3 mg/kg FK506, respectively. After treatment, the functional integrity of the transplanted human islets was tested by measuring the plasma glucose and human C-peptide response to intraperitoneal glucose injection in groups 1 and 4. IPGTT alone was assessed in groups 2 and 3. The results indicate that i.p. administration of FK506 for one week at a dose 0.3 mg/kg/day did not result in any significant alteration of glucose disappearance and C-peptide response to IPGTT. Higher doses of FK506 produced a significant delay in glucose disappearance in groups 3 and 4, and a significant inhibition of glucose-mediated C-peptide response in group 4.
Ricordi
C
C
Department of Surgery, University of Pittsburgh, Pennsylvania 15213.
Zeng
Y J
YJ
Alejandro
R
R
Tzakis
A
A
Venkataramanan
R
R
Fung
J
J
Bereiter
D
D
Mintz
D H
DH
Starzl
T E
TE
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D013045:Species Specificity; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D002096:C-Peptide; D007166:Immunosuppressive Agents; D007328:Insulin; D016559:Tacrolimus