In episode 23, I explained why ketogenesis isn't all about carbs and insulin. Here in episode 25, I explained why insulin resistance isn't all about carbs and insulin. If that doesn't sound crazy, let me put it this way: forget carbs; I'll even say insulin resistance isn't all about insulin. We start with a riddle: what do obesity, exercise, cigarette smoking, and diets rich in fruits and vegetables all share in common? Hint: it's a centrally important physiological response to each of them that mediates their health effects. In the course of answering this riddle, I explain the underlying physiology that I consider most important to "insulin resistance" and why I believe insulin resistance is best viewed as subset of something far more important. I conclude by outlining practical strategies to prevent and reverse it. In this episode, you will find all of the following and more: Why would an individual cell "decide" to stop responding to insulin?; the limitations of using blood insulin and glucose concentrations as a primary metric of insulin resistance are similar to the limitations of assessing your level of "boss resistance" by the number of phone calls you decline from your boss when you skip work; why your pancreas is sort of like your boss; reactive oxygen species (ROS) are central to the physiology; ROS inhibit aconitase and shunt internal energy toward fat storage; ROS inhibit further intake of energy; ROS inhibit fatty acid uptake into mitochondria; ROS inhibit glucose uptake; ROS increase the expression of the entire antioxidant system and xenobiotic defense system; Subbing players on the field in team sports provides a useful analogy to understand why ROS-mediated inhibition of cellular energy uptake is health-promoting when other cells can fill in; insulin resistance isn't all about insulin; some responses to cellular energy overload antagonize insulin; others mimic insulin; obesity vs. exercise; AMPK activation makes the net effects of ROS in exercise very different from obesity; micronutrient intake determines whether net effects of ROS support antioxidant defense; glutathione synthesis depends on both nutrients and insulin sensitivity and stimulation; insulin resistance isn't all about ROS. It's about the context in which ROS operate; the net hormetic pro-oxidant effects of fruits and vegetable polyphenol; the net toxic pro-oxidant effects of cigarette smoking; again, net effects of ROS aren't about ROS; their about the context in which ROS operate; nutrient density as a practical strategy in insulin resistance; body composition as a practical strategy in insulin resistance; low-carbohydrate diets as a useful practical strategy for body composition, with potential limitations in the long-term because of the importance of carbohydrates for antioxidant defense.