ABSTRACT. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat has poor capacity for proliferation of pancreatic β-cells after partial pancreatectomy, which may be the critical pathogenetic event in NIDDM development. The poor pancreatic β-cell proliferation in this model is characterized by reduction in β-cell mass and decrease in insulin content in the remnant pancreas. Our investigation was designed to identify quantitative trait loci (QTLs) responsible for β-cell mass and plasma insulin levels after partial pancreatectomy by performing a genome-wide scan in an F 2 intercross obtained by mating the OLETF and the Fischer-344 (F344) rats. We have identified a suggestive QTL for the plasma insulin levels, near D20Mgh5 on rat chromosome 20, with a maximum lod score of 3.75 which accounts for 20% of the total variance, while no QTLs were detected for β-cell mass. This chromosome 20 QTL, whose OLETF allele is associated with low plasma insulin levels through acting in an incompletely recessive manner, may affect insulin secretion itself rather than β-cell proliferation. -KEY WORDS: NIDDM, OLETF rat, QTL.J. Vet. Med. Sci. 60(10): 1157-1160, 1998 Hirashima and Kawano, and inbred Fischer-344 (F344) rats were obtained from Charles River Japan, Inc. (Yokohama, Japan). We arranged crosses between female OLETF and male F344 rats to produce 98 male F 2 progeny. Only male rats at 6 weeks of age at the beginning of the study were subjected to 70% pancreatectomy for genetic studies. After an overnight fast, animals were anesthetized with ether and given additional ether if needed during surgery. All pancreatic tissue was removed by gentle abrasion with cotton applicators, except for an anatomically well-defined remnant bordered by the branch of the hepatic portal vein and the first portion of the duodenal loop. After surgery, the rats had food and water available ad libitum. Nonfasting plasma insulin concentrations were measured at 28 days after surgery. Blood samples were obtained by tail snipping, and non-fasting insulin concentrations in the plasma were determined by a commercially available kit (Eiken Kagaku, Tokyo, Japan) based on radioimmunoassay with rat insulin (Novo, Bagsvared, Denmark) as a standard. Pancreas was excised and cleared of extraneous lymph nodes and fat at 28 days after surgery. The pancreas was weighed and cassetted with the same anatomic orientation, placed in Bouin's fixative, and processed for paraffin embedding using a standard protocol. For the measurement of β-cell mass, two sets of three serial sections (3-5 µm thick) were obtained at intervals of ~250 mm. The sections were first deparaffined and then immunostained for insulin by using ABC kit (Amersham, UK). The primary antibody used was polyclonal guinea pig anti-porcine insulin antibody (1:400, Dako Carpinteria). Using Weibel's point-counting morphometrics [13], the relative volume of β-cells was quantitated at 200 × magnification using a 9...