β-cell regeneration to treat Type 1 diabetes mellitus

Abstract

Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of the insulin-producing pancreatic β-cells. The autoimmune response begins years before the presentation of hyperglycemic symptoms. At the time of clinical diagnosis, less than 30% of β-cell mass still remains. The conventional therapeutic option to T1DM is daily insulin injections, which is shown to promote tight glucose control and reduce the majority of chronic diabetic complications. Subgroup analysis of the Diabetes Control and Complication Trial showed another important aspect related to long-term complications of diabetes, that is, patients with initially higher serum levels of C-peptide with sustained levels over the subsequent years suffered less microvascular complications and less hypoglycemic events than those patients with low or undetected C-peptide levels. In face of this, β-cell preservation is another important target in the management of T1DM and its related complications. Along the years, many efforts toward the identification of precursors of β-cells have been made, not only with the aim of understanding the physiology of β-cell preservation, but also as a potential source of β-cell replacement. In this review, we summarize the most important studies related to probable precursor cells implied in the process of regeneration, and the results of various immunomodulatory regimens aiming at blocking autoimmunity against pancreatic β-cells and at promoting β-cell preservation. Finally, we comment on the future perspective related to stem cell therapy in T1DM.