Enhancing islet engraftment with rosiglitazone.
To study the role of a peroxisome proliferator-activated receptor agonist, rosiglitazone, on islet engraftment, streptozotocin-induced diabetic C57BL/6 mice were fed daily rosiglitazone (2.4 mg/kg) for 9 and 31 days starting 2 days before transplantation with 75 and 150 syngeneic islets, respectively. After receiving 75 islets and 9 days of rosiglitazone, half of the treated diabetic mice became normoglycemic at 4 weeks, while none were normoglycemic among those mice that did not receive treatment. After transplanting 150 islets and receiving 31 days of rosiglitazone, 80% of the treated diabetic mice became normoglycemic while the incidence was only 25% for the controls. The insulin content of the islet grafts in the rosiglitazone groups was 0.8 times (75-islet group) and 1.3 times (150-islet group) higher than that of control mice. The insulin content of pancreatic remnants did not differ significantly among all groups. An in vitro study revealed that the glucose-stimulated insulin secretion and insulin content of cultured islets was not different in the presence versus absence of 4.5 or 22.5 micromol/L rosiglitazone. In vitro study revealed that rosiglitazone inhibited the lipopolysaccharide-induced secretion of interleukin-1 beta and interferon-gamma from peritoneal exudate cells. In conclusion, our data suggest that short-term administration of rosiglitazone enhances islet engraftment.
Hsu
B R-S
BR
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang-Gung Memorial Hospital, Taoyuan Hsien, Taiwan, Taiwan. bh0658@adm.cgmh.org.tw
Fu
S-H
SH
Ku
K-W
KW
Yang
T-Y
TY
Juang
J-H
JH
Chen
S-T
ST
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012016:Reference Values; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014185:Transplantation, Isogeneic
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone