Relationship between β-cell mass and diabetes onset

Aleksey V. Matveyenko, P. C. Butler

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Regulation of blood glucose concentrations requires an adequate number of β-cells that respond appropriately to blood glucose levels. β-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 β-cell mass ranging from 0 to 65% in type 2 diabetes (T2DM), and ∼70-100% in type 1 diabetes (T1DM), and, when evaluated, increased β-cell apoptosis in both T1DM and T2DM. A deficit of β-cell mass of ∼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 β-cell cytotoxicity (autoimmune in T1DM, unknown in T2DM) leading to impaired β-cell function and gradual loss of β-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 β-cell dysfunction and insulin resistance. The relative contribution of β-cell loss versus β-cell dysfunction to diabetes onset remains an area of controversy. However, because cytotoxicity sufficient to induce β-cell apoptosis predictably disturbs β-cell function, it is naïve to attempt to distinguish the relative contributions of these linked processes to diabetes onset.

Original languageEnglish (US)
Pages (from-to)23-31
Number of pages9
JournalDiabetes, Obesity and Metabolism
Volume10
Issue numberSUPPL. 4
DOIs
StatePublished - Jan 1 2008

Keywords

  • Pulsatile insulin secretion
  • Type 1 diabetes
  • Type 2 diabetes
  • β-cell apoptosis
  • β-cell mass

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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