Spontaneous Long-Term Hyperglycemic Rat With Diabetic Complications: Otsuka Long-Evans Tokushima Fatty (OLETF) Strain

A spontaneously diabetic rat with polyuria, polydipsia, and mild obesity was discovered in 1984 in an outbred colony of Long-Evans rats, which had been purchased from Charles River Canada (St. Constant, Quebec, Canada) in 1982. A strain of rats developed from this rat by selective breeding has since been maintained at the Tokushima Research Institute (Otsuka Pharmaceutical, Tokushima, Japan) and named OLETF. The characteristic features of OLETF rats are 1) late onset of hyperglycemia (after 18 wk of age); 2) a chronic course of disease; 3) mild obesity; 4) inheritance by males; 5) hyperplastic foci of pancreatic islets; and 6) renal complication (nodular lesions). Histologically, the changes of pancreatic islets can be classified into three stages: 7) an early stage (6–20 wk of age) of cellular infiltration and degeneration; 2) a hyperplastic stage (20–40 wk of age); and 3) a final stage (at >40 wk of age). These clinical and pathological features of disease in OLETF rats resemble those of human NIDDM.