Islet β cell mass in diabetes and how it relates to function, birth, and death.
In type 1 diabetes (T1D) β cell mass is markedly reduced by autoimmunity. Type 2 diabetes (T2D) results from inadequate β cell mass and function that can no longer compensate for insulin resistance. The reduction of β 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 β 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 β 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 β cell mass in both types of diabetes could be accomplished by either β cell regeneration or transplantation. Learning more about the relationships between β cell mass, turnover, and function and finding ways to restore β cell mass are among the most urgent priorities for diabetes research.
Section on Islet Cell Biology and Regenerative Medicine, Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA. gordon.weir@joslin.harvard.edu
Gordon C
GC
Weir
Susan
S
Bonner-Weir
D000818:Animals; D016923:Cell Death / Q000502:physiology; D048429:Cell Size; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology* / Q000502:physiology