@article{4ddfe04d2723458e8789a7b9f4bebe0b,
title = "Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia",
abstract = "Insulin genese expression is restricted to islet β cells of the mammalian pancreas through specific control mechanisms mediated in part by specific transcription factors. The protein encoded by the pancreatic and duodenal homeobox gene 1 (PDX-1) is central in regulating pancreatic development and islet cell function. PDX-1 regulates insulin gene expression and is involved in islet cell-specific expression of various genes. Involvement of PDX-1 in islet-cell differentiation and function has been demonstrated mainly by 'loss-of-function' studies. We used a 'gain-of- function' approach to test whether PDX-1 could endow a non-islet tissue with pancreatic β-cell characteristics in vivo. Recombinant-adenovirus-mediated gene transfer of PDX-1 to the livers of BALB/C and C57BL/6 mice activated expression of the endogenous, otherwise silent, genes for mouse insulin 1 and 2 and prohormone convertase 1/3 (PC 1/3). Expression of PDX-1 resulted in a substantial increase in hepatic immunoreactive insulin levels, compared with that in mice treated with control adenovirus. Hepatic immunoreactive insulin induced by PDX-1 was processed to mature mouse insulin 1 and 2 and was biologically active; it ameliorated hyperglycemia in diabetic mice treated with streptozotocin. These data indicate the capacity of PDX-1 to reprogram extrapancreatic tissue towards a β-cell phenotype, may provide a valuable approach for generating 'self' surrogate β cells, suitable for replacing impaired islet-cell function in diabetics.",
author = "Sarah Ferber and Amir Halkin and Hofit Cohen and Idit Ber and Yulia Einav and Iris Goldberg and Iris Barshack and Rhona Seijffers and Juri Kopolovic and Nurit Kaiser and Avraham Karasik",
note = "Funding Information: Acknowledgments We thank C. Gal, Y. Cohen, Y. Ariav, P. Keren, A. Shaish, M. Tal and D. Castel for technical support; M.D. Walker and C.B. Newgard for critically reviewing the manuscript; R. Skutelsky and H. Halkin for editing the manuscript; and B. Goldman for support. The study was partially supported by a grant from Israel Ministry of Health-Mendel Chodowski-Fund.",
year = "2000",
month = may,
doi = "10.1038/75050",
language = "אנגלית",
volume = "6",
pages = "568--572",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Research",
number = "5",
}