Abstract
A hallmark of type 2 diabetes (T2DM) is the reduction in functional β-cell mass, which is considered at least in part to result from an imbalance of β-cell renewal and apoptosis, with the latter being accelerated during metabolic stress. More recent studies, however, suggest that the loss of functional β-cell mass is not as much due to β-cell death but rather to de-differentiation of β-cells when these cells are exposed to metabolic stressors, opening the possibility to re-differentiate and restore functional β-cell mass by therapeutic intervention. In parallel, clinical observations suggest that temporary intensive insulin therapy in early diagnosed humans with T2DM, so as to "rest" endogenous β-cells, allows these patients to regain adequate insulin secretion and to maintain euglycemia for prolonged periods free of continued pharmacotherapy. Whether observations made in (mostly rodent) models of diabetes mellitus and in clinical trials are revealing identical mechanisms and therapeutic opportunities remains a tantalizing possibility. Our intention is for this review to serve as an overview of the field and commentary of this particularly exciting field of research.