Reversal of streptozotocin-induced hyperglycemia by transplantation of pseudoislets consisting of beta cells derived from ductal cells.
The present study was conducted in an attempt to treat streptozotocin (STZ)-induced hyperglycemia by transplanting beta cells derived from pancreatic ductal cells. Ductal cells obtained from neonatal rats were cultured in vitro. Approximately 70% of the cells were converted to insulin-secreting cells by incubating with betacellulin and activin A. Differentiated cells responded to a depolarizing concentration of potassium, tolbutamide and a high concentration of glucose, and insulin secretion increased by 2.5-, 2.3- and 1.6-fold, respectively. We then prepared pseudoislets using the differentiated cells, which exhibited greatly improved glucose-responsiveness, with a high concentration of glucose inducing a 3-fold increase in insulin secretion. We transplanted these pseudoislets into the portal vein of STZ-treated nude mice. Before transplantation, the plasma glucose concentration was above 400 mg/dl, and after transplantation it was markedly reduced, the effect of which persisted for two weeks. These results indicate that STZ-induced hyperglycemia can be treated by transplanting pseudoislets consisting of beta cells derived from ductal cells.
Ogata
Takeki
T
Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
Park
Kee Young
KY
Seno
Masaharu
M
Kojima
Itaru
I
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006943:Hyperglycemia / Q000139:chemically induced / Q000601:surgery*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010183:Pancreatic Ducts / Q000166:cytology* / Q000637:transplantation*; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin