Insulin Resistance and Bears
If you read popular science magazines, you’ve probably seen the recent research about hibernating grizzly bears and insulin resistance. You can see a few articles here, here, here, and here. This story clearly appeals to science magazines and gives them a good chance to publish cute photos of fat bears dozing.
The abstract of the original article has some useful diagrams and the lead author of the study, Kevin Corbit, kindly sent me the full article.
Bears put on a lot of weight in the fall, and then they doze all winter and live off their fat. They can even give birth and nurse their young without eating.
Corbit and his colleagues showed that while the grizzly bears are rapidly gaining weight in the fall, they are very insulin sensitive. Insulin tells fat cells to turn glucose into fat and keeps fat cells from breaking down fat.
Then when they’re hibernating, the bears become very insulin resistant. This allows their fat cells to break down the stored fat and use it for energy.
The researchers found that this difference in insulin sensitivity between early fall and winter is controlled by a molecule called PTEN. When PTEN is turned down, they become insulin sensitive and put on weight. When PTEN is turned up, they become insulin resistant and lose weight. And this variation in PTEN is found only in the fat cells.
Interestingly, some humans who have a genetic defect in PTEN are very insulin sensitive and put on weight very easily.
So what is fascinating about this research is the idea that insulin resistance is not always bad and insulin sensitivity is not always good, as was previously thought. Insulin resistance in the fat cells keeps you from gaining fat and helps you to burn the fat you already have.
On the other hand, insulin resistance in all your cells keeps you from taking glucose out of the bloodstream and hence makes your blood glucose levels go up. So we don’t want that either. In the hibernating bears, glucose levels remained normal despite the high insulin resistance in the fat cells.
Some of the popular articles equated the insulin resistance in the bears to diabetes. Insulin resistance is associated with type 2 diabetes in humans, but if you or the bears have normal blood glucose levels despite insulin resistance, you don’t have diabetes.
It’s important to note that we are not bears. I suppose that’s obvious, but the physiology of bears is not always the same as our own. For example, bears store fat only in their fat cells, whereas humans may also get fatty livers and muscles. Furthermore, insulin resistance patterns in some other hibernators, such as marmots, are different from those of the bears. The bear system is not universal.
We’re not mice either, and many of the supposed diabetes cures in mice turn out not to apply to humans, which is one reason Corbit and colleagues wanted to study obesity/diabetes physiology in larger mammals.
Some analysts have hinted that if we could only figure out how to control PTEN in humans, we could control insulin resistance and type 2 diabetes. But in the bears and the people with genetic lack of PTEN, the lack of insulin resistance leads to obesity, which is just trading one health problem for another.
Perhaps genetically increased insulin sensitivity could make people put on weight easily. Then once they were fat, the body might increase insulin resistance in an effort to control the weight. If you’re hunting and gathering, obesity would be a liability. But researchers tend not to measure insulin resistance before people get fat. And they don’t usually try to measure insulin resistance in different tissues.
So we don’t know yet how much of this interesting research will turn out to be applicable to human obesity and diabetes. However, it does open up new avenues of research.
And it’s yet-another suggestion of how insulin can control obesity. We don’t yet have a way to alter PTEN levels in our fat cells. But high insulin levels in a person with insulin resistance would have the same effect on fat burning as lower insulin levels in a person who was very insulin sensitive. Eating fewer carbohydrates reduces our insulin levels and this should allow our fat cells to burn fat, preferably our own fat, as the fat cells do in the hibernating bears.
Because carbohydrate makes insulin levels increase the most, it’s another reason a low-carbohydrate diet is helpful to people who have weight problems.
Remember I pointed out that we are not bears. I’m assuming none of the readers of this blog are bears. But, to paraphrase a famous cartoon, “On the Internet, no one knows you’re a bear.”