In a healthy human, an injection of insulin will cause a drop in blood sugar as the hormone facilitates the transport of sugars from the blood into cells, where it is either used to produce energy or stored as fuel. In a diabetic subject, the cells fail to respond to the insulin and their blood sugar stays high — with long-term effects like obesity, hypertension and cardiovascular disease.
But bears are able to modulate their insulin responsiveness, so that when they are most obese, in the fall, they are most insulin sensitive. In other words, even as they pile on the pounds, their cells retain the capacity to take instructions from insulin.
Just weeks later, the bears render themselves completely insulin resistant while in hibernation; they become, in essence, diabetic. But hibernating bears differ from diabetic humans in that they maintain normal blood sugar levels while in this insulin-resistant state. Once they wake, in the spring, the grizzlies restore their insulin responsiveness. So bears modulate insulin sensitivity not to maintain normal blood sugar levels but to control when fat is stored and when it is broken down. Put another way, bears naturally and reversibly succumb to diabetes. Since we know when they make this switch, we hope to pinpoint how they do this.
Grizzlies also handle obesity in a much different manner than humans — without tissue inflammation or storing fat where it does harm. Bears store their winter fuel only in fat tissue, not in the liver or in muscle, as occurs in humans with pathological obesity. These findings suggest that bears have mastered a kind of “healthy” maintenance obesity — despite huge fat accumulation, weight gain and perpetually high cholesterol.
This phenomenon of healthy obesity may also occur in a small number of humans with specific mutations in a gene known as PTEN, such that, while obese, they remain exquisitely sensitive to insulin. Thus humans with this mutation are quite grizzly-like in their metabolism.
Interestingly, we have found that bears control the activity of PTEN, the protein encoded by the PTEN gene, in a manner similar to a dimmer switch, cranking the activity up and down at specific times of the year to control how responsive to insulin they are. As we know exactly when bears modulate PTEN activity and where (in fat cells), we expect to discover the mechanism.
Millions of years of evolutionary experimentation have produced genetic adaptations that enabled bears to cope with obesity, converting it to a benign state in which weight gain has much-reduced health threats. If nature has figured this stuff out for grizzlies, maybe we can for humans.