Relationship Between Beta-Cell Mass and Diabetes Onset

Diabetes Obes Metab. 2008 Nov;10 Suppl 4(0 4):23-31. doi: 10.1111/j.1463-1326.2008.00939.x.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Autopsy
  • B-Cell Activating Factor / metabolism*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Disease Models, Animal
  • Humans
  • Insulin Resistance / physiology*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / physiology*
  • Liver / metabolism*
  • Liver / physiopathology
  • Receptor, Insulin / physiology

Substances

  • B-Cell Activating Factor
  • Blood Glucose
  • Receptor, Insulin