Identification of a Quantitative Trait Locus Influencing Plasma Insulin Levels after 70% Pancreatectomy Using the OLETF Rat

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 F₂ 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.