Renal function tests on diabetes-induced and non-induced APA hamsters.

Although it has been said that Syrian hamsters of the APA strain (APA hamsters) spontaneously develop glomerulosclerosis with age, more prominent and severe glomerulosclerosis with proteinuria as well as arteriosclerosis is induced in diabetic APA hamsters. In this study, in order to supply new information on APA hamsters, tests on renal function and histology were done on non-diabetic and streptozotocin (SZ)-induced diabetic APA hamsters (APA-N and APA-D, respectively), and the data were compared with those of normal Syrian (golden) hamsters (GOL). At 4, 8, 12, 20, and 32 weeks of age, the markers indicating renal function, serum urea nitrogen and creatinine levels and the urinary total protein level were measured and thereafter histological studies were done. Although there were no remarkable differences between APA-N and GOL in serum urea nitrogen and creatinine levels, APA-N excreted more urinary total protein from the early weeks of age. In APA-D, an apparent worsening in these markers indicating renal function was detected and diabetic nephropathy in this model was confirmed also in terms of renal function. In the histological studies, the major lesion observed in APA-D was diffuse glomerulosclerosis. This may mean that renal dysfunction in APA-D was mainly caused by the glomerular change and that it is similar to other experimental diabetic animals and human diabetic patients. These data show that the diabetic APA hamster is a desirable model of human diabetic nephropathy.

Expression of lipoprotein receptors in the aortic walls of diabetic APA hamsters.

Syrian hamsters of the APA strain (APA hamsters) have recently been demonstrated to develop atheromatous lesions in the aortic arches under the diabetic condition induced by a single injection of streptozotocin (SZ). Various lipoprotein receptors are reported to play important roles in atherogenesis mainly in vitro, while there are few reports on the relative expressions of these receptors in vivo. In this study, we therefore examined messenger RNA (mRNA) expressions of several lipoprotein receptors on the aortic arches of diabetic APA hamsters at 6, 14 and 26 weeks after the injection (WAI) of SZ. In semi-quantitative RT-PCR, scavenger receptor (SR)-AI, macrosialin (MS)/CD68, and receptor for advanced glycation end-products (RAGE) mRNAs showed significant increases at 6 WAI of SZ, and SR-AI and CD36 mRNA obviously increased until 26 WAI, as compared with the control. Low-density lipoprotein receptor mRNA showed a significant decrease at 14 and 26 WAI, and SR-BI mRNA significantly decreased at 6 and 14 WAI, as compared with the control. Very low-density lipoprotein receptor mRNA was at the same level as the control. By means of in situ hybridization, SR-AI, MS/CD68 and RAGE mRNA were detected in the foam cells of the fatty streaks at 6 WAI, which suggested that SR-AI, MS/CD68 and RAGE play crucial roles in the formation of the fatty streaks, the initial lesions of atherogenesis in diabetic APA hamsters. SR-AI and CD36 were also believed to be related to the progression of atherogenesis in this model.

Functional and histochemical analysis on pancreatic islets of APA hamsters with SZ-induced hyperglycemia and hyperlipidemia.

To clarify how Syrian hamsters of the APA strain (APA hamsters) keep a diabetic condition for a long period, the functional and histochemical changes in the pancreatic islets of diabetic APA hamsters were examined. By glucose tolerance test, no glucose-induced insulin secretion was seen in the diabetic APA hamsters. By immunohistochemistry, it was revealed that at 24 hr after SZ-injection, the number of islets had decreased and that remnant islets had become markedly smaller. The islets had hardly any insulin-immunoreactive cells and consisted of cells stained by anti-glucagon and somatostatin antibodies. One, three and six months after SZ-injection, a small number of cells with vacuolative changes, which were positive for PAS staining, were observed in most islets and the vacuolated cells were stained mainly by anti-insulin antibody. In addition, a number of PCNA-positive cells were observed, especially in the periphery of the vacuolated cells, while TUNEL-positive cells were not detected. This data suggests that beta-cells proliferating as a result of the replication of the resident beta-cells in islets had fallen into degeneration and necrosis by a stress, such as the glycogen deposition in hyperglycemia and hyperlipidemia. Consequently, secretion of insulin was maintained at low levels, which allowed the hamsters to live without insulin therapy in the diabetic condition for over 6 months.