What if there’s enough insulin, but the insulin doesn’t work? The key is there, but something’s gummed up the lock. This is insulin resistance. Our muscle cells become resistant to the effect of insulin. What’s gumming up the locks on our muscle cells? What’s preventing insulin from letting glucose in? Tiny droplets of fat inside our muscle cells, so-called intramyocellular lipid.
Fat in the bloodstream can build up inside the muscle cell, creating toxic fatty breakdown products and free radicals that block the insulin signaling process. No matter how much insulin we have in our blood, it’s not able to sufficiently open the glucose gates and blood sugar levels build up in the blood. And this can happen within three hours. One hit of fat can start causing insulin resistance, inhibiting blood sugar uptake after just 160 minutes.
This mechanism by which fat induces insulin resistance wasn’t known until fancy MRI techniques were developed to see what was happening inside people’s muscles as fat was infused into their bloodstream. That’s how we found that elevation of fat levels in the blood causes insulin resistance by inhibition of glucose transport into the muscles.
We can also do the opposite experiment. Lower the level of fat in people’s blood and the insulin resistance comes right down. If we clear the fat out of the blood, we also clear the sugar out. That explains the finding that on the high fat, ketogenic diet, insulin doesn’t work very well. Our bodies become insulin resistant. But as the amount of fat in our diet gets lower and lower, insulin works better and better—a clear demonstration that the sugar tolerance of even healthy individuals can be impaired by administering a low-carb, high-fat diet. We can decrease insulin resistance, however, by decreasing fat intake.