Endocrine Abstracts (2009) 20 P336

Comparative molecular analysis of TRAIL ligand and receptor expression profiles in cyclophosphamide versus streptozotocin-induced diabetes in non-obese diabetic (NOD) mice

Sevim Kahraman1, Ercument Dirice1, Ozlem Elpek1, Mustafa Kemal Balci1, Abdulkadir Omer2, Salih Sanlioglu1 & Ahter Sanlioglu1


1Akdeniz University, Antalya, Turkey; 2Harvard Medical School, Boston, Massachusetts, USA.


Background: NOD mice are the most frequently preferred animal models in type 1 diabetes (T1D) research. They develop spontaneous disease in 24 to 30 months. T1D can also chemically be induced in NOD mice for a faster disease progression. Two commonly used diabetes-inducing agents are Streptozotocin (STZ), which destructs pancreatic beta cells mainly through DNA fragmentation, and Cyclophosphamide (CY), which acts on suppressor T cells. TNF-Related Apoptosis-Inducing Ligand (TRAIL) has recently been implicated in T1D development. Although its exact role is unknown, blockage of TRAIL sensitized animals to T1D development. Here, we aimed to examine the effects and diabetes-inducing profiles of Streptozotocin and Cyclophosphamide in NOD mice, while comparatively analysing alterations in TRAIL ligand and receptor expression profiles.

Materials and methods: Diabetes development was accelerated in mice by IP injection of 200 mg/kg CY or 150 mg/kg STZ. Blood sugar measurements were used to monitor development of diabetes. Pancreatic tissues were collected at days 0, 1, 2, 4, 7, 14, 21, and 28. Alterations in TRAIL ligand and receptor expression profiles were detected by immunohistochemistry.

Results: STZ produced a faster T1D profile, as reflected by blood sugar levels of 250 mg/dl and over at day 4, accompanied by a 10% weight loss. Nearly 90% of mice were diabetic at day seven. CY-induced NOD mice, on the other hand, did not develop any signs of diabetes until after day 10. Both agents were generally well-tolerated in mice at the mentioned doses. STZ- or CY- induced pre-diabetic to severly diabetic mice revealed significant alterations in TRAIL ligand and receptor expression patterns.

Conclusion: Both agents induced prominent manifestation of T1D, although at different time intervals. Comparative analysis of alterations in TRAIL ligand and receptor expression patterns revealed an important insight into the molecular pathogenesis of T1D.

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