Relationship between beta-cell mass and diabetes onset.
Regulation of blood glucose concentrations requires an adequate number of beta-cells that respond appropriately to blood glucose levels. beta-Cell mass cannot yet be measured in humans in vivo, necessitating autopsy studies, although both pre- and postmorbid changes may confound this approach. Autopsy studies report deficits in beta-cell mass ranging from 0 to 65% in type 2 diabetes (T2DM), and approximately 70-100% in type 1 diabetes (T1DM), and, when evaluated, increased beta-cell apoptosis in both T1DM and T2DM. A deficit of beta-cell mass of approximately 50% in animal studies leads to impaired insulin secretion (when evaluated directly in the portal vein) and induction of insulin resistance. We postulate three phases for diabetes progression. Phase 1: selective beta-cell cytotoxicity (autoimmune in T1DM, unknown in T2DM) leading to impaired beta-cell function and gradual loss of beta-cell mass through apoptosis. Phase 2: decompensation of glucose control when the pattern of portal vein insulin secretion is sufficiently impaired to cause hepatic insulin resistance. Phase 3: adverse consequences of glucose toxicity accelerate beta-cell dysfunction and insulin resistance. The relative contribution of beta-cell loss versus beta-cell dysfunction to diabetes onset remains an area of controversy. However, because cytotoxicity sufficient to induce beta-cell apoptosis predictably disturbs beta-cell function, it is naive to attempt to distinguish the relative contributions of these linked processes to diabetes onset.
Matveyenko
A V
AV
Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-7073, USA. amatveyenko@mednet.ucla.edu
Butler
P C
PC
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001344:Autopsy; D053264:B-Cell Activating Factor / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D011972:Receptor, Insulin / Q000502:physiology
D053264:B-Cell Activating Factor; D001786:Blood Glucose; D011972:Receptor, Insulin