Generation of insulin-secreting cells from adult rat pancreatic ductal epithelial cells induced by hepatocyte growth factor and betacellulin-delta4.
The present study was conducted to identify effective factors that could induce differentiation of pancreatic ductal epithelial cells (PDECs) into insulin-producing cells. We examined the effect of hepatocyte growth factor (HGF) and betacellulin-delta4 (BTC-delta4) on PDECs. We isolated PDECs from adult rats and stimulated them with HGF and BTC-delta4 for 28days. We observed several characteristics of PDECs after induction, including functional changes in PDECs, differentiation rate, and expression levels of critical transcription factors. We observed that insulin content and glucose-induced insulin secretion were significantly higher in induced PDECs compared to control PDECs. The expression of markers specific to mature beta-cells, i.e., insulin and glucose transporter-2 (GLUT2) was also observed. An analysis of the expression of different transcription factors (PDX-1, Ngn3, NeuroD, and Pax4) revealed that cell-specific gene expression patterns varied from 7 to 28days after treatment. Hence, we conclude that treatment with a combination of HGF and BTC-delta4 is effective in inducing the differentiation of PDECs into insulin-secreting cells.
Zhan
Xiao-Rong
XR
Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province, PR China. xiaorongzhan@sina.com
Li
Xin-Yu
XY
Liu
Xiao-Min
XM
Zhou
Jian-Hua
JH
Yang
Yu-Ling
YL
Yi
Ran
R
Zhang
Jing
J
Yang
Bao-Feng
BF
D000818:Animals; D066259:Betacellulin; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000096:biosynthesis
D066259:Betacellulin; C587853:Btc protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor