Preservation of β-cell function by targeting β-cell mass

Type 2 diabetes is characterized by progressive β-cell dysfunction and a reduction in β-cell mass. Pancreatic islets are a target for adverse effectors such as high concentrations of glucose, pro-inflammatory cytokines and increased free fatty acid concentrations – which are associated with adiposity, insulin resistance and the induction of β-cell apoptosis. If the β-cell mass is already below the threshold for maintaining normoglycemia, the expansion of β-cell mass is the only option for achieving normoglycemia without the use of additional glucose-lowering agents. Therapies based on glucagon-like peptide-1 and combinations of growth factors such as epidermal growth factor and gastrin are promising new strategies for β-cell preservation. In this review, we address the mechanisms involved in β-cell dysfunction and β-cell loss, and provide a rationale for pharmacological intervention for the preservation and/or expansion of β-cell mass in type 2 diabetes.