Purpose: Approximately 50% of islet grafts are destroyed within 72 hours after pancreatic islet transplantation (PITx) due to non-specific inflammatory responses. Previously, we reported that inhibition of NF-ΚB activation shortly after PITx prevents graft loss in mice. A PPAR-Γ agonist exerts anti-inflammatory effect via NF-ΚB inhibition. The effect of Proliferator-activated receptor (PPAR)-Γ agonist on islet graft loss was examined in a canine auto-PITx model.
Methods: Diabetes was induced in beagle dogs by a total pancreatectomy. Islets isolated from the extracted pancreas were auto-transplanted into the liver through the portal vein. To determine the marginal islet number, 500, 1000 or 2000 IEQ/kg islets were transplanted (n=5-7). A PPAR-Γ agonist, pioglitazone (PIO), was given p.o. 1 hour before and twice daily thereafter for 3 days (n=7). Fasting blood glucose level (FBGL) was monitored daily. An intravenous glucose tolerance test (IVGTT) was performed on day 14 after PITx.
Results: Following PITx with 500, 1000 or 2000 IEQ/kg islets, FBGL normalized in 0% (0/6), 42.9% (3/7), 80% (4/5) of islet recipients, respectively. PITx with 1000 IEQ/kg islets was defined as marginal (Control). Treatment with PIO at 5 mg/kg improved the normal glycemic rate to 71.4% (5/7, p=0.32). When PIO was given at 10 mg/kg, FBGL normalized in all PITx animals (7/7, p<0.05) (Fig.1). The calculated BGL-AUC 0-120 after IVGTT in the control, PIO 5 mg/kg and PIO 10 mg/kg groups was 34758±4315, 27778±5509 (p=0.34) and 18949±553 mg*min/dl (p<0.01), respectively.
Conclusion: A PPAR-Γ agonist, PIO prevents early islet graft loss and maintains normoglycemia in canine PITx.
To cite this abstract in AMA style:Asahi Y, Yamashita K, Watanabe M, Ogura M, Ono H, Handly E, Emoto S, Nagatsu A, Yoshida T, Koshizuka Y, Kamachi H, Taketomi A, Todo S. Prevention of Early Graft Loss by Proliferator-Activated Receptor-γ Agonist, Pioglitazonoe, in Canine Islet Autotransplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/prevention-of-early-graft-loss-by-proliferator-activated-receptor-agonist-pioglitazonoe-in-canine-islet-autotransplantation/. Accessed December 3, 2023.
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