Optimized STZ treatment leads to specific cytotoxicity of insulin-producing cells. Optimized STZ treatment leads to specific cytotoxicity of insulin-producing cells. Images are representative of guinea pigs developing hyperglycemia after treatment with an optimized SC dose of anomer-equilibrated STZ at 200 mg/kg administered after an intramuscular injection of yohimbine. (A) Pancreatic islets from a nondiabetic, normal-diet control guinea pig (arrow) demonstrating histological morphology in the absence of diabetogenic treatment. (B) Morphological changes 48 h after STZ treatment in pancreas of a guinea pig with confirmed hyperglycemia that was fed a normal diet. Cell death has occurred in the majority of islet cells (arrowheads), while a minority of the cells remain viable. (C) Immunofluorescent detection of pro-insulin (green) in pancreatic islets in a normal-diet control guinea pig indicates that the majority of islet cells are insulin-producing β cells (blue, Hoechst nuclear counterstain). (D,E) Immunofluorescent detection of pro-insulin in a guinea pig 48 h after receiving an optimized dose of STZ. Disruption of cellular and nuclear morphology is uniform across all islets and is specific to insulin-expressing β cells (arrows and inset). Scale bar: 100 µm. Brendan K. Podell et al. Dis. Model. Mech. 2017;10:151-162 © 2017. Published by The Company of Biologists Ltd