title: β-cell loss and β-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition.
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.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Jurgens
authors.forename: Mirna N
authors.initials: MN
authors.lastname: Toukatly
authors.forename: Corinne L
authors.initials: CL
authors.lastname: Fligner
authors.forename: Jayalakshmi
authors.initials: J
authors.lastname: Udayasankar
authors.forename: Shoba L
authors.initials: SL
authors.lastname: Subramanian
authors.forename: Sakeneh
authors.initials: S
authors.lastname: Zraika
authors.forename: Kathryn
authors.initials: K
authors.lastname: Aston-Mourney
authors.forename: Darcy B
authors.initials: DB
authors.lastname: Carr
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
authors.forename: Gunilla T
authors.initials: GT
authors.lastname: Westermark
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hull
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism*; D017209:Apoptosis; D016022:Case-Control Studies; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000682:Amyloid