Islet β cell mass in diabetes and how it relates to function, birth, and death

In type 1 diabetes (T1D) beta cell mass is markedly reduced by autoimmunity. Type 2 diabetes (T2D) results from inadequate beta cell mass and function that can no longer compensate for insulin resistance. The reduction of beta cell mass in T2D may result from increased cell death and/or inadequate birth through replication and neogenesis. Reduction in mass allows glucose levels to rise, which places beta cells in an unfamiliar hyperglycemic environment, leading to marked changes in their phenotype and a dramatic loss of glucose-stimulated insulin secretion (GSIS), which worsens as glucose levels climb. Toxic effects of glucose on beta cells (glucotoxicity) appear to be the culprit. This dysfunctional insulin secretion can be reversed when glucose levels are lowered by treatment, a finding with therapeutic significance. Restoration of beta cell mass in both types of diabetes could be accomplished by either beta cell regeneration or transplantation. Learning more about the relationships between beta cell mass, turnover, and function and finding ways to restore beta cell mass are among the most urgent priorities for diabetes research.