β-cell loss and β-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition

Am J Pathol. 2011 Jun;178(6):2632-40. doi: 10.1016/j.ajpath.2011.02.036.

Abstract

Amyloid deposition and reduced β-cell mass are pathological hallmarks of the pancreatic islet in type 2 diabetes; however, whether the extent of amyloid deposition is associated with decreased β-cell mass is debated. We investigated the possible relationship and, for the first time, determined whether increased islet amyloid and/or decreased β-cell area quantified on histological sections is correlated with increased β-cell apoptosis. Formalin-fixed, paraffin-embedded human pancreas sections from subjects with (n = 29) and without (n = 39) diabetes were obtained at autopsy (64 ± 2 and 70 ± 4 islets/subject, respectively). Amyloid and β cells were visualized by thioflavin S and insulin immunolabeling. Apoptotic β cells were detected by colabeling for insulin and by TUNEL. Diabetes was associated with increased amyloid deposition, decreased β-cell area, and increased β-cell apoptosis, as expected. There was a strong inverse correlation between β-cell area and amyloid deposition (r = -0.42, P < 0.001). β-Cell area was selectively reduced in individual amyloid-containing islets from diabetic subjects, compared with control subjects, but amyloid-free islets had β-cell area equivalent to islets from control subjects. Increased amyloid deposition was associated with β-cell apoptosis (r = 0.56, P < 0.01). Thus, islet amyloid is associated with decreased β-cell area and increased β-cell apoptosis, suggesting that islet amyloid deposition contributes to the decreased β-cell mass that characterizes type 2 diabetes.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid / metabolism*
  • Apoptosis*
  • Case-Control Studies
  • Demography
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Amyloid