Paul Saladino· MD
so I think that this seems to start in the fat and then it kind of depends on I think the person but like some people will argue that it starts in the muscle if you're super sedentary yeah that might be the case but what it's essentially the cell saying I do not have the ability or the desire to process the nutrients that you're sending me that's what instant resistance it it's like a suitcase that's full yeah you can't pack anymore t-shirts in there yeah and that's either because the capacity is decreased right because say because there's injury to your mitochondria or and you know that directly feeds back to the instance receptor or your a fat cell and you're just like stuffed full of fat and you just can't take anymore and then you start saying oh no mass no more so with regard to fat I want people to understand the fat cells are cells they have a nucleus they have mitochondria they have a big vacuole in which you put fat yeah but they have a cell they have into plasmic reticulum they make proteins they are a living cell it's not just a bag of fat it's an organ yeah it's a hormonal ly active organ they secrete adipic Ines and they have unique nutrients and that's again when I talked about with my HS talk but like Tommy is saying perhaps insulin resistance starts in the fat but many cell types many organs can become insulin resistant deliver the muscle to fat and they sort of refuse the actions of insulin they say no no no I'm not gonna respond to you insulin is a peptide hormone that circulates and generally binds to its receptor which i gf1 can also bind to in signals hey take up glucose through the glute for transporter yeah and when it's resistant it's just like a irascible child says and I ain't cleaning my room I'm not taking that up anymore and it's a protective effect yeah it's a protective effect because the mitochondria are damaged or that the there is just overload of cellular energy and all these things and so I think I need to do a whole Cass on insulin resistance the mechanisms are fascinating I talked a little bit about it in the recent podcast with Dave and Siobhan but the way that I think about insulin resistance is a couple of things can cause it one of them is oxidative stress related to perhaps too much energy and glucose in the podcast I did with Dom D'Agostino he talked about glucose metabolism in some people predisposing to higher levels of oxidative stress through superoxide dismutase in the mitochondrial electron transport chain and higher production of hydrogen peroxide that isn't actually able to be transformed into or higher production of excuse me the peroxide radical or the hydroxyl radical that can't be transformed into the other intermediates and so it is also clear that inflammation in the body whether it's responding to an infection or an oxidative stress can trigger insulin resistance as I talked about with Dave and Siobhan that's probably an evolutionary mechanism by which we shown tree sources yeah and we trigger the immune system to be more active and I think it's getting activated you know inappropriately today because we're exposed to more oxidative stress it's not an inflammatory issue per se in the sense that it's not an infectious issue yeah but the body has a system in place whereby it responds to infectious issues with inflammation and insulin resistance yeah okay that is awesome I think hopefully that'll be a good discussion I don't think we can ever talk about insulin resistance too much so and but one thing that that really bothers me and in the insulin resistance space is that so like Tim Noakes has recently gone a lot of like good publicity because he's been he's been writing blogs for the CrossFit website talking about like why a cardiovascular diseases the insulin resistance and like yes that's true but what is it that causes in services like you don't just get you know aegis it's not contagious you don't just get it spontaneously so yes insulin resistance may be the causative or like the the thing that that binds all these problems together but what is it that causes insulin resistance and it's that this eeveelution mismatch the the lack of these factors that you know in terms of good nutrition sleep movement maybe even social connection which act you know if you're socially isolated that inadvertently or inappropriately activates the immune system so all of this stuff is why against the resistance so when people talk about while I'm instant resistant therefore I reduce my carbohydrate intake yes you can't do that but it doesn't really make any sense to me because I'm fixed what caused the insulin resistance in the first place it wasn't just eating too many carbohydrates like because there are plenty of there are plenty of populations around the world who do all the things that