Mechanisms of Pancreatic β-Cell Death in Type 1 and Type 2 Diabetes

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FIG. 4.
FIG. 4.

Morphology of an islet from a diabetic IDDM (LEW.1AR1/Ztm-iddm) rat (A–C) exhibiting hyperglycemia (21.4 mmol/l) and hypoinsulinemia (0.5 ng/ml) 1 day after diabetes manifestation and of an islet from a type 2 diabetes Psammomys obesus (sand rat) (D–F) exhibiting hyperglycemia (17.5 mmol/l) and hyperinsulinemia (1.8 ng/ml) after 3 weeks on a high-energy diet. The sections were immunostained for IL-1β (A and D), iNOS (B and E), and activated caspase-3 (C and F) and show cytoplasmic immunoreactivities only in the infiltrated islets of the type 1 diabetic animal (A–C). Infiltrating immune cells in the diabetic IDDM rat (A–C) are mostly ED1+ macrophages (arrows) and CD8+ T-cells (arrowheads). These cells express immunoreactivity for IL-1β (A) and iNOS (B) but not for activated caspase-3 (C). Pancreatic β-cells undergoing apoptosis (thick arrows), in contrast, express immunoreactivity for iNOS and activated caspase-3, but not for IL-1β. The few infiltrating immune cells in the islet of a diabetic Psammomys obesus (D–F) are exclusively ED1+ macrophages (arrows). These cells show no signs of immunoreactivity for IL-1β (D), iNOS (E), or activated caspase-3 (F). β-Cells (thick arrows) of Psammomys showed signs of necrotic destruction including intra- and intercellular vacuolization without expression of IL-1β (D), iNOS (E), or activated caspase-3 (F). These β-cells showed no signs of nuclear heterochromatin condensation. The same findings were made after 1 week of a high-energy diet. ED1+ macrophages, CD8+ T-cells, and pancreatic β-cells were identified by sequential sections immunostained with specific antibodies against the given cell type as previously described (67,86) (data not shown). Original magnification ×400.

This Article

  1. Diabetes vol. 54 no. suppl 2 S97-S107