Transgenic mice expressing IFN-gamma in pancreatic beta-cells are resistant to streptozotocin-induced diabetes.

In 28 adult Ins-IFN-gamma transgenic mice, injection of high doses of streptozotocin (STZ; first injection, 300 microgram/g body weight; second injection, 200 microgram/g body weight 4 h later) failed to induce severe hyperglycemia. To the contrary, 28 BALB/c mice developed diabetes mellitus after identical injections of STZ. Because the STZ-induced islet damage was partially inhibited in Ins-IFN-gamma transgenic mice, their glycemia levels became normal 4 days after STZ administration. Both transgenic and BALB/c mice lost weight after receiving STZ, but the body weights of transgenic mice then returned to pretreatment levels in a nearly parallel manner with the glycemia. Immunolabeling with insulin identified an unusual spreading pattern of insulin immunoreactivity. Ultrastructural observations confirmed that beta-cell necrosis and degranulation were more severe in STZ-treated BALB/c than in Ins-IFN-gamma transgenic mice. Moreover, regeneration of pancreatic duct cells and islet neogenesis were observed in the transgenic mice. Therefore, after STZ treatment, the Ins-IFN-gamma transgenic mice apparently were resistant to the induction of severe diabetes, whereas their BALB/c age-matched counterparts succumbed to the disease.