Prolonged effect of troglitazone (CS-045) on xenograft survival of hybrid artificial pancreas.
Troglitazone (CS-045), a thiazolidinedione derivative, is a new oral antidiabetic agent that enhances insulin sensitivity and improves insulin responsiveness. In this study we examined the effects of CS-045 on the survival of xenografted bioartificial pancreas. Isolated rat islets were microencapsulated with three-layer agarose microcapsules (polybrene, carboxymethyl cellulose, and an agarose-polystyrene sulfonic acid mixture). Diabetes was induced by intraperitoneal injection of streptozotocin 220 mg/kg. Recipient diabetic mice were separated into two groups. In the CS-045 treated group, the recipient mice were given feed mixed with CS-045 (0.2% w/w) starting from 1 wk before transplantation up to graft failure. The mice in the control group had feed without CS-045. Three hundred microencapsulated rat islets were xenotransplanted into the intraperitoneal cavity of each recipient mouse in both groups. One month after xenotransplantation, IVGTT was performed for all recipients. Xenotransplantation of 300 rat islets in microcapsules decreased the nonfasting blood glucose levels of both groups within 2 days. In the CS-045-treated group (n = 3), the normoglycemic period lasted for more than 1 mo without administration of immunosuppressive drugs (45 +/- 4.3 days). However, in the control group (n = 4), the blood glucose levels of all recipients were already elevated on day 4. In the IVGTT study, the glucose assimilation was markedly and significantly better in the CS-045-treated group than in the control group (K = 1.7 +/- 0.1 vs. 0.7 +/- 0.28 respectively, p < 0.01). This study demonstrates that a newly developed oral antidiabetic agent, CS-045 could favorably ameliorate the diabetic state of the recipients xenotransplanted with the bioartificial pancreas, leading to an improved glucose tolerance and longer xenograft survival.
Kawakami
Y
Y
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Inoue
K
K
Tun
T
T
Hayashi
H
H
Setoyama
H
H
Gu
Y J
YJ
Cui
W X
WX
Imamura
M
M
Iwata
H
H
Ikada
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D002839:Chromans / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced; D005951:Glucose Tolerance Test; D006085:Graft Survival / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019397:Pancreas, Artificial; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014183:Transplantation, Heterologous; D000077288:Troglitazone
D001786:Blood Glucose; D002214:Capsules; D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone