ABSTRACT
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 colony by selective breeding has since been maintained at the Tokushima Research Institute Otsuka Pharmaceutical (Tokushima, Japan), and is now referred to as the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The characteristic features of OLETF rats include: 1) late onset hyperglycemia (after 18 weeks of age), 2) a chronic disease state, 3) Increased urinary protein excretion at about 30 weeks of age. 4) higher glomerular filtration rate (GFR) compared with that of LETO rat, a strain derived from the same colony of Long-Evans rats that does not exhibit the diabetic syndrome; 4) Increased kidney weight and glomerular hypertrophy; 5) Decreased number of polyethyleneimine (PEI) in the glomerular basement membrane (GBM) in OLETF rats compared with LETO rats. Foot processes are irregularly arranged and retraction. Furthermore, the GBM showed marked thickening and rupture. 6) histological change of the kidney was focal mesangial lesion with proliferation of mesangial cells at 23 weeks of age. Glomerular damage progresses chronically and exudative lesions appear at 29 weeks of age. Most of glomeruli become obsolescent with severe atrophy of tubules after 90 weeks of age, resembling the advanced stage of human diabetic nephropathy. The glomerular lesions found in OLETF rats are similar to human diabetic nephropathy, and are characterized by fibrin cap, capsular drop and aneurysmal dilatations of intraglomerular vessels. Thus, the clinical and pathological features of the disease state in OLETF rats resemble those of human renal complications in type 2 diabetes.
