The BB Rat
Diabetes-prone BioBreeding (BBDP) rats develop a spontaneous diabetic syndrome resembling human type 1 diabetes (T1D). Foremost, BBDP rats lose the majority of their beta cells during a rapid and aggressive inflammation of the islets during the last 2 weeks prior to overt hyperglycemia (1 ). Once hyperglycemia occurs, the rats become highly polyuric – they may lose well over 20 g (10–15% of body weight) overnight despite an excessive drinking behavior – and they proceed within 24–48 h to become ketotic. They die in ketoacidosis unless rescued by exogenous insulin therapy within the first 2 days of hyperglycemia (2, 3) – i.e. this clearly separates their diabetic phenotype from that of NOD mice that can easily survive for longer time after the onset of clinical diabetes. Indeed, within the first week, all insulin release and immunoreactivity in the pancreas is entirely lost – i.e. the phenotype of hypoinsulinemia is complete in BBDP rats (4–7).