Sunday, June 27, 2021

Insulin Resistance: Mechanism

 We all know that insulin resistance (IR) is one of the main causes of type 2 diabetes. Many people with type 2 can produce some insulin, but it's just not enough to overcome the IR.

What causes this sluggishness? No one knows for sure.

A recent paper suggests that the key is ATP, the energy-containing molecule that is produced when you eat and can then be used to drive other reactions in the cell.

I always thought ATP was good to have, and the more ATP the more energy. But this author (Jianping Ye) suggests that too much ATP can cause what he calls overheating. In the winter, it's nice to get heat from your furnace; the heat is nice, but you don't want it to get up to 100 degrees. He suggests the same is true of ATP.

Ye says that when you have too much ATP, the cells become insulin resistant to prevent overburdening the cells with too much energy. Hence, cells are insulin sensitive under conditions of energy deficiency and insulin resistant when there's an energy surplus.

So insulin sensitivity/resistance is an index of energy demand.

Interestingly the drug metformin inhibits ATP production.

He notes that as we age, energy demand decreases. If you're 95, you're not apt to go out and play three sets of tennis, so you need less food.

We all know that, but many of us eat portions determined by habit rather than by need. Restaurants don't serve meals adjusted for need. Everyone gets the same thing, although of course someone who just spent the day mountain climbing can order more than someone who spent the day reading. But how many of us act on that? In our "clean plates club" society, we often eat more than we really need. This is especially true in people who eat all their meals out.

In support of Ye's hypothesis, it has been known for about 60 years that elevated ATP is a risk factor for insulin resistance. But he says its importance hasn't been appreciated because of technical difficulties in measuring ATP in various tissues.

Interestingly the drug metformin inhibits ATP production

So is one solution to the diabetes epidemic simply to eat less? Sadly, that's often difficult to do. If  you eat out a lot, one solution is to get a tightly sealed container, carry it in a nice handbag, and use it to take at least half of the meal home without carrying around those awful plastic things restaurants usually put leftovers into.

We need food. We need energy. We need ATP. But as with many things in our lives, we just don't need too much.

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