Salk Institute for Biological Studies

The Role of Insulin Resistance in Protection Against Gastrointestinal Infection

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Insulin resistance precedes type 2 diabetes and metabolic syndrome. However, it has been proposed that short-lived insulin resistance may be advantageous during times of stress, likely by diverting limited nutrients for tissue repair and survival. The goal of our research is to investigate the physiological role of insulin resistance during bacterial infection. Data from our lab show that insulin resistance improves infectious disease outcomes. We observe that diet-induced and pharmacologically-induced insulin resistance protects mice from killing by the gastrointestinal pathogen Citrobacterrodentium. Surprisingly insulin resistance drives attenuation of C. rodentiumin vivo, allowing mice to persistently carry this pathogen with no indication of disease. We hypothesize that insulin resistance is a physiological adaptation which allows the body to tolerate pathogens and prevent infection-related damage to the body. Given the increasing prevalence of community-and hospital-infections by antibiotic-resistant pathogens, this research may lead to new therapeutic strategies that leverage transient insulin resistance and host metabolism mechanisms to control infections.