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Title 

Activin A, exendin-4, and glucose stimulate differentiation of human pancreatic ductal cells

Authors 

H S KimSeung Hyun HongS H OhJ H KimM S LeeM K Lee

Publisher 

BioScientifica

Issue Date 

2013

Citation 

Journal of Endocrinology, vol. 217, no. 3, pp. 241-252

Keywords 

Activin ADifferentiationExendin-4GlucoseHuman pancreatic ductal cells

Abstract 

Islet transplantation is one treatment option for diabetes mellitus. However, novel sources of pancreatic islets or insulin-producing cells are required because the amount of donor tissue available is severely limited. Pancreatic ductal cells are an alternative source of b-cells because they have the potential to differentiate into insulin-producing cells. We investigated whether treatment of human pancreatic ductal cells with activin A (ActA) and exendin-4 (EX-4) stimulated transdifferentiation of the cells, both in vitro and in vivo. We treated human pancreatic ductal cells with ActA and EX-4 in high-glucose media to induce differentiation into insulin-producing cells and transplanted the cells into streptozotocin-induced diabetic nude mice. Co-treatment of mice with ActA and EX-4 promoted cell proliferation, induced expression of pancreatic b-cell-specific markers, and caused glucose-induced insulin secretion compared with the ActA or EX-4 mono-treatment groups respectively. When pancreatic ductal cells treated with ActA and EX-4 in high-glucose media were transplanted into diabetic nude mice, their blood glucose levels normalized and insulin was detected in the graft. These findings suggest that pancreatic ductal cells have a potential to replace pancreatic islets for the treatment of diabetes mellitus when the ductal cells are co-treated with ActA, EX-4, and glucose to promote their differentiation into functional insulin-producing cells.

ISSN 

0022-0795

Link 

http://dx.doi.org/10.1530/JOE-12-0474

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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