NEWS & VIEWS glucose transporter, Glut2, and of a hexokinase, glucokinase. The only two tissues with such a sensor are pancreatic β cells and liver hepatocytes4. However, the liver is devoid of the specific prohormone convertases (PC1 and PC3) needed to process the weakly active proinsulin into the mature hormone, and also lacks the regulated secretory mechanisms. Several groups have reported the transfection of hepatocytes with a transgene that is directed by a glucose-sensitive promoter and encodes a mutated ‘pre-pro-insulin’cleavable by the ubiquitous convertase furin5, 6. Unfortunately, secretion of insulin by such engineered hepatocytes has so far remained qualitatively and quantitatively very different from that by normal β cells. It is difficult to envisage that hepatocyte-mediated insulin secretion could be further improved by transferring the entire set of genes encoding secretory machinery of the endocrine cell type. Therefore, other approaches that rely on the differentiation plasticity of endogenous cells must be considered.

Ramiya et al. have reported that large numbers of islet cells could be derived from pancreatic ductal epithelial cells removed from prediabetic non-obese diabetic mice and expanded in culture7. After being transplanted into diabetic mice, these cells led to a considerable reduction in blood glucose7. However, the availability of such cells in adult diabetic