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

ABSTRACT

Amyloid deposition and reduced ß-cell mass are pathological hallmarks of the pancreatic islet in type 2 diabetes; however, whether the extent of amyloid deposition is associated with decreased ß-cell mass is debated. We investigated the possible relationship and, for the first time, determined whether increased islet amyloid and/or decreased ß-cell area quantified on histological sections is correlated with increased ß-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 ß cells were visualized by thioflavin S and insulin immunolabeling. Apoptotic ß cells were detected by colabeling for insulin and by TUNEL. Diabetes was associated with increased amyloid deposition, decreased ß-cell area, and increased ß-cell apoptosis, as expected. There was a strong inverse correlation between ß-cell area and amyloid deposition (r = -0.42, P < 0.001). ß-Cell area was selectively reduced in individual amyloid-containing islets from diabetic subjects, compared with control subjects, but amyloid-free islets had ß-cell area equivalent to islets from control subjects. Increased amyloid deposition was associated with ß-cell apoptosis (r = 0.56, P < 0.01). Thus, islet amyloid is associated with decreased ß-cell area and increased ß-cell apoptosis, suggesting that islet amyloid deposition contributes to the decreased ß-cell mass that characterizes type 2 diabetes.