An investigation into diabetes-related outcomes in a rat model, with senior author William Valdar, PhD, assistant professor of genetics at UNC, and first author Leah Solberg Woods, PhD, from the Medical College of Wisconsin, has made the editor’s pick in this month’s Physiological Genomics, a journal of the American Physiological Society.
The article is titled, “Fine-mapping diabetes-related traits, including insulin resistance, in heterogeneous stock rats.” It was published in the Nov. 1, 2012, issue of Physiological Genomics, and was selected as an Editor’s Pick in January 2013.
Abstract:
“Type 2 diabetes (T2D) is a disease of relative insulin deficiency resulting from both insulin resistance and beta cell failure. We have previously used heterogeneous stock (HS) rats to fine-map a locus for glucose tolerance. We show here that glucose intolerance in the founder strains of the HS colony is mediated by different mechanisms: insulin resistance in WKY and an insulin secretion defect in ACI, and we demonstrate a high degree of variability for measures of insulin resistance and insulin secretion in HS rats. As such, our goal was to use HS rats to fine-map several diabetes-related traits within a region on rat chromosome 1. We measured blood glucose and plasma insulin levels after a glucose tolerance test in 782 male HS rats. Using 97 SSLP markers, we genotyped a 68 Mb region on rat chromosome 1 previously implicated in glucose and insulin regulation. We used linkage disequilibrium mapping by mixed model regression with inferred descent to identify a region from 198.85 to 205.9 that contains one or more quantitative trait loci (QTL) for fasting insulin and a measure of insulin resistance, the quantitative insulin sensitivity check index. This region also encompasses loci identified for fasting glucose and Insulin_AUC (area under the curve). A separate