Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes.
We recently found that pancreatic acinar cells isolated from normal adult mouse can transdifferentiate into insulin-secreting cells in vitro. Using two different animal models of type 1 diabetes, we show here that insulin-secreting cells can also be generated from pancreatic acinar cells of rodents in the diabetic state with absolute insulin deficiency. When pancreatic acinar cells of streptozotocin-treated mice were cultured in suspension in the presence of epidermal growth factor and nicotinamide under low-serum condition, expressions of insulin genes gradually increased. In addition, expressions of other pancreatic hormones, including glucagon, somatostatin, and pancreatic polypeptide, were also induced. Analysis by the Cre/loxP-based direct cell lineage tracing system revealed that these newly made cells originated from amylase-expressing pancreatic acinar cells. Insulin secretion from the newly made cells was significantly stimulated by high glucose and other secretagogues. In addition, insulin-secreting cells were generated from pancreatic acinar cells of Komeda diabetes-prone rats, another animal model of type 1 diabetes. The present study demonstrates that insulin-secreting cells can be generated by transdifferentiation from pancreatic acinar cells of rodents in the diabetic state and further suggests that pancreatic acinar cells represent a potential source of autologous transplantable insulin-secreting cells for treatment of type 1 diabetes.
Okuno
Masaaki
M
Division of Cellular and Molecular Medicine, Kobe Univ. Graduate School of Medicine, Kobe 650-0017, Japan. seino@med.kobe-u.ac.jp
Minami
Kohtaro
K
Okumachi
Akinori
A
Miyawaki
Kazumasa
K
Yokoi
Norihide
N
Toyokuni
Shinya
S
Seino
Susumu
S
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000150:complications; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010179:Pancreas / Q000254:growth & development; D046790:Pancreas, Exocrine / Q000166:cytology*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
D007328:Insulin; D013311:Streptozocin