Insulinoma-associated protein 2-deficient mice develop severe forms of diabetes induced by multiple low doses of streptozotocin
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- Published online on: July 1, 2009 https://doi.org/10.3892/ijmm_00000201
- Pages: 23-27
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Abstract
Insulinoma-associated protein 2 (IA-2) is the major autoantigen that contributes to the pathogenesis of type 1 diabetes (T1D). IA-2-deficient (IA-2−/−) mice showed impaired insulin secretion after intraperitoneal injection of glucose as well as elevated glucose level in a glucose tolerance test. Despite the fact that 70% of newly diagnosed T1D patients have an antibody against IA-2, the role of IA-2 in the pathogenesis of T1D is largely unknown. In this study, the sensitivity to diabetes induced by streptozotocin (STZ) of IA-2−/− mice was compared with that of wild-type (WT) mice. STZ injection to IA-2−/− mice caused significant elevation of blood glucose and depressed insulin concentration in the pancreas. Furthermore, abnormal ultrastructure in the β cells of the IA-2−/− mice was revealed by electron microscopy, showing a decreased number of insulin containing vesicles and dilation of the ER-Golgi complex. These results demonstrated that IA-2−/− mice had higher sensitivity to STZ, suggesting a role of IA-2 not only in the secretion but also in the production of insulin.