Surrogate β-cells

New work indicates that the liver can be induced to serve as a surrogate for the pancreas, with a little help from the PDX-1 gene. By injecting mice with an adenoviral vector containing the gene encoding PDX-1, a homeodomain protein involved in the development and differentiation of pancreatic cells, a group of researchers from Israel has succeeded in converting a subpopulation of liver cells to a pancreatic β-cell phenotype. Following adenoviral treatment, about 60% of the mice liver cells started synthesizing PDX-1, with a 25-fold increase in insulin expression, 59% of which was fully processed functional protein. In an experimental model of diabetes in which hyperglycemia was induced by the chemical streptozotocin, the researchers found that only those mice treated with the PDX-1 gene were able to survive and ameliorate glucose dysregulation. It is not yet clear whether the surrogate β-cells can respond normally to fluctuations in glucose or whether, like β-cells, they themselves will become targeted by autoimmune processes. But according to Axel Kahn, a diabetes researcher at INSERM (Paris), the results “could constitute a breakthrough in the prospects of therapy for type I diabetes,” which currently affects up to 14 million people worldwide. The findings are reported in Nat. Med. (6, 568–572, 2000).

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Marshall, A. Surrogate β-cells. Nat Biotechnol 18, 585 (2000).

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