Tatsuo Tomita1. 1. Department of Pathology, and Oregon National Primate Center, Oregon Health and Science University, Portland, OR 97006, USA. tomitat@ohsu.edu
Abstract
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Anita V Neutzsky-Wulff; Kim V Andreassen; Sara T Hjuler; Michael Feigh; Anne-Christine Bay-Jensen; Qinlong Zheng; Kim Henriksen; Morten A Karsdal Journal: J Transl Med Date: 2012-10-30 Impact factor: 5.531