Immunocytochemical localisation of caspase-3 in pancreatic islets from type 2 diabetic subjects

Caspase-3 has been recognised as a main effector caspase of the apoptotic cascade. Involvement of caspase-3 has been implicated in a beta-cell cloned cell line from type 1 diabetic subjects and in isolated islets from type 2 diabetic subjects. This study aimed to immunocytochemically identify cleaved caspase-3 positive islet cells in type 2 diabetic subjects compared with control subjects.

Using commercially available rabbit anti-cleaved caspase-3 antibody, immunocytochemical staining was performed on 16 cases of pancreatic tissues from type 2 diabetic subjects compared with age-matched controls.

Control islets revealed cleaved caspase-3 positive cells in about 4.7% in total islet cells with large and small islets positive at 4.1% and 7.0%, respectively. Islets from type 2 diabetic subjects showed higher immunostaining percentage at 8.7% in total islets with large and small islets positive for cleaved caspase-3 at 7.7% and 12%, respectively, at about twice that of the control values. Islets from type 2 diabetics were generally insulin cell-less and glucagon cell-rich, but insulin cells still remained. Type 2 diabetic islets showed various stromal amyloid deposits, displacing the residual islet cells. Cleaved caspase-3 positive cells were more in the less amyloid deposited islets than in the islet cell deficient islets containing more amyloid deposits; the latter correspond to the end-stage of type 2 diabetic islets.

The more cleaved caspase-3 immunostained islets from type 2 diabetics may implicate an accelerated apoptotic cascade in the islets, accompanied by increasing amyloid deposits, before proceeding to ultimate cell death.