Effect of Probucol on the Apoptosis of Pancreatic Islet Cells in Multiple Low Dose Streptozotocin Induced Diabetic (LDSD) Mice

Choi, Kyung Mook; Kim, Dong Rim; Kim, Nan Hee; Kim, Chul Hwan; Baik, Sei Hyun; Choi, Dong Seop

Abstract

BACKGROUND: Type 1 Diabetes Mellitus(DM) is consequence of pancreatic beta cell destruction by immune interactions of auto-reactive T cells and cytokines. In individuals with genetic predisposition, an environmental insult triggers immune reaction against beta cells to produce clinical type 1 DM. Since the capacity to form new beta cells from precursors and power of replication appear to be limited, the susceptibility of beta cell to death may be the major underlying variable influencing the occurrence of type 1 DM. However, the precise mechanism of beta cell death is not known. Apoptosis is a physiologic form of cell death and recent studies reported that it could play an important role in beta cell death in experimental diabetic animal models such as multiple low dose streptozotocin diabetic (LDSD) mice or non- obese diabetic (NOD) mice. Probucol is a hypocholesterolemic agent with antioxidant properties. Some studies reported that the probucol could reduce the blood glucose level in type 1 animal models but the mechanism was not known. Therefore, this study was performed to define whether the probucol could decrease the degree of hyperglycemia and the mechanism of its attenuation on the severity of pancreatic insulitis by reducing the degree of apoptosis in LDSD mice.
METHODS
We performed an experimental study with male Charles-River CD-1 mice. Mice were divided into the 30 streptozotocin-induced diabetics, 30 probucol- treated streptozotocin-induced diabetics. At 1, 5, 10, 15, and 20 days after streptozotocin administration, the blood glucose level was measured and mice were sacrificed to determine the grade of insulitis and apoptosis. The numbers of apoptotic cells of pancreatic islets were compared using double staining immunohistochemical method (TUNEL and insulin antibody staining).
RESULTS
The level of blood glucose and the severity of insulitis were decreased in the probucol treated LDSD mice group significantly when compared with the control LDSD mice group. The numbers of apoptotic cells of pancreatic islets were decreased in the probucol group. The appearance of apoptosis of beta cells preceded the development of insulitis in LDSD mice.
CONCLUSION
Probucol can reduce blood glucose level and the severity of insulitis by the decrease of apoptosis in LDSD mice.