The present invention relates to a method for reprogramming a somatic cell (e.g. a pancreatic ductal cell, a skin fibroblast or a keratinocyte) to a pancreatic β-cell. This method involves decreasing expression or activity of Fbw7 and/or decreasing phosphorylation-mediated degradation of NGN3 in the somatic cell. The method may be carried out ex vivo or in vivo. The invention also relates to a method of treating a subject with a metabolic disorder (e.g. diabetes) or a subject at risk of a metabolic disorder by administering somatic cells that have been re-programmed to pancreatic β-cells using methods described herein to the subject. In addition, the invention relates to screening methods for identifying a candidate agent for reprogramming a somatic cell to a pancreatic β-cell.
