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Ferber, S, Halkin, A, Cohen, H, Ber, I, Einav, Y, Goldberg, I, Barshack, I, Seijffers, R, Kopolovic, J, Kaiser, N and Karasik, A (2000) Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat. Med. 6:568-72


Insulin gene expression is restricted to islet beta 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 beta-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 content and an increase of 300% in plasma 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 beta-cell phenotype, may provide a valuable approach for generating 'self' surrogate beta cells, suitable for replacing impaired islet-cell function in diabetics.


PubMed Online version:10.1038/75050


Adenoviridae/genetics; Animals; Aspartic Acid Endopeptidases/analysis; Duodenum; Gene Therapy/methods; Genes, Homeobox; Homeodomain Proteins; Hyperglycemia/chemically induced; Hyperglycemia/therapy; Insulin/blood; Islets of Langerhans; Liver/metabolism; Mice; Mice, Inbred C57BL; Proprotein Convertases; Streptozocin/pharmacology; Trans-Activators/therapeutic use



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


GO:0010468: regulation of gene expression



Fig 1 shows that the mice with the AdCMV-PDX-1 gene (in lanes 2-8), all show insulin production, whereas the control groups do not.

CACAO 5211



GO:0010468: regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion


Seeded From UniProt


See also


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