What Causes Insulin Resistance?

What Causes Insulin Resistance?


What Causes Insulin Resistance? Studies dating back nearly a century noted
a striking finding. If you take young, healthy people, split them up into two groups, half on a fat-rich diet, and half on a carb
rich diet, within just two days, this is what happens. The glucose intolerance skyrockets in the
fat group. In response to the same sugar water challenge, the group that had been shoveling in fat ended up with twice the blood sugar. As the amount of fat in the diet goes up,
so does our blood sugar spikes. Why would eating fat lead to higher blood
sugar levels? It would take scientists nearly seven decades to unravel this mystery, but it would end up holding the key to our
current understanding of the cause of type 2 diabetes. The reason athletes carb load before a
race is to build up the fuel supply within their muscles. We break down the starch into glucose in our digestive tract; it circulates as blood glucose, also known
as blood sugar, and is taken up by our muscles to be stored and burnt for energy. Blood sugar, though, is like a vampire. It needs an invitation to come into our cells. And that invitation is insulin. Here’s a muscle cell. Here’s some blood sugar outside waiting
patiently to come in. Insulin is the key that unlocks the door to
let the sugar in our blood enter the muscle cell. When insulin attaches to the insulin receptor, it activates an enzyme, which activates another enzyme, which activates two more enzymes, which finally activates glucose transport, which acts as a gateway for glucose to enter the cell. So insulin is the key that unlocks the door
into our muscle cells. What if there was no insulin though? Well, blood sugar would be stuck out in the bloodstream banging on the door to our muscles and not able to get inside, and so with nowhere to go sugar levels would rise and rise. That’s what happens in type 1 diabetes. The cells in the pancreas that make insulin
get destroyed, and without insulin sugar in the blood can’t get out of the
blood into the muscles, and blood sugar rises. But there’s a second way we could end up
with high blood sugar. 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 called insulin resistance. Our muscle cells become resistant to the effect of insulin. What’s gumming up the door locks on our
muscle cells preventing insulin from letting sugar in? Fat. What’s called intramyocellular lipid,
fat inside our muscle cells. Fat in the bloodstream can build up inside
the muscle cell, creating toxic fatty breakdown products and free radicals that can block the insulin
signaling pathway process. So no matter how much insulin we have out in our blood, it’s not able to open the glucose gates, and blood sugar levels build up in the blood. 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 out that elevation of
fat levels in the blood causes insulin resistance by inhibition of
glucose transport into the muscles. And this can happen within three hours. One hit of fat can start causing insulin resistance, inhibiting glucose uptake after just 160 minutes. Same thing happens to teens. You infuse fat into their bloodstream. It builds up in their muscles and decreases
their insulin sensitivity, showing that increased fat in the blood is
an important contributor of insulin resistance. And then you can do the opposite experiment. Lower the level of fat in people’s blood
and the insulin resistance comes right down. Clear the fat out of the blood, and you clear the sugar out of the blood. So that explains this finding. 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. This is a clear demonstration that the sugar tolerance of even healthy individuals can be impaired by administering a low-carb high-fat diet. But we can decrease insulin resistance by
decreasing fat intake.