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.
Gu
D
D
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Arnush
M
M
Sawyer
S P
SP
Sarvetnick
N
N
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance; D007371:Interferon-gamma / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D010179:Pancreas / Q000473:pathology; D012038:Regeneration / Q000187:drug effects; D013311:Streptozocin / Q000494:pharmacology
D001786:Blood Glucose; D013311:Streptozocin; D007371:Interferon-gamma; D001973:Bromodeoxyuridine