Spontaneously diabetic rat “OLETF” as a model for NIDDM in humans

Abstract

A spontaneous polyuria, polydipsia, and mild obesity was discovered in 1984 in an outbred colony of Long Evans (LE) rats, that had been purchased from Charles River Canada (St. Constant, Quebec, Canada) in 1982. A strain of rats was developed by selective breeding from this rat and designated OLETF (Otsuka Long-Evans Tokushima Fatty). The OLETF line has been maintained since then by brother-sister mating at the Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd.1.2 From the same LE colony stock, a line developing insulin-dependent diabetes mellitus (IDDM) has been isolated (LETL)3-4 and a control line, LETO, has also been established. General and basic kinetic studies on OLETF rats have been described in the previous report 2 and are summarized as follows: 1) After 24 wk of age, elevation of plasma glucose and immunoreactive insulin, and the oral glucose tolerance test (OGTT), became marked, indicating diabetes mellitus. These increases were more prominent at 55 wk. At 65 wk of age, plasma glucose levels rose to >22.4 mmol/l and the insulin values became <40 pmol/l. 2) The cumulative incidences of diabetes and impaired glucose tolerance (IGT) were 87.8% (341 of 388) and 7.2% (28 of 388), respectively, in male OLETF rats after the 20th generation. Female OLETF rats displayed diabetes in very few individuals at 30 wk of age, though approximately 33.3% (5 of 15) of females showed diabetes when 60 wk old. On the contrary, no diabetic rat was found among LETO rats. 3) Male OLETF rats began to gain weight faster than LETO rats beginning at 5 wk, and the difference gradually increased with age, being about 200 g at 40 wk of age.