Genetic Variations in <i>GCKR</i> and <i>PNPLA3</i> Regulate Metabolic Balance Across the Liver

We examined genetic variation in GCKR and PNPLA3 for association with type 2 diabetes-related traits in Mexican Americans without diabetes. We addressed three questions: Are these loci associated with type 2 diabetes-related traits? Is there interaction between these loci? Is there interaction with dietary sugars? These loci individually, and in an interaction, are associated with type 2 diabetes-related traits; these loci also interact with dietary fructose to alter hepatic glucose uptake. Our findings support the hypothesis that these loci, coupled with dietary fructose and total sugars, alter hepatic metabolic balance and may contribute to hepatic fat and insulin resistance.