Given that you’ve found your way to this blog, you are probably aware of the fact that obesity is associated with a glut (pun intended) of comorbidities (other conditions), not the least serious of which is type 2 diabetes. Whereas type 1 diabetes is caused by an autoimmune response directed against the insulin-producing beta islet cells of the pancreas, type 2 diabetes is caused by exhausting those beta cells through excessive energy consumption.
Essentially, if one eats too much and has high blood glucose levels, the beta cells have to produce more and more insulin to keep up, eventually leading to accumulation of damage and death. It’s important to note that this is a gradual and distressingly feed-forward process, since as weight is gained, the body becomes less sensitive to insulin and more of it has to be produced to compensate. This state is referred to as insulin resistance, and it is considered to be a major contributor to the further development of type 2 diabetes.
A major problem encountered by scientists seeking to study obesity and diabetes is that treatments developed in mice have failed to have any impact on humans, underlying their limited utility as a model organism for the disease. Given this stumbling block, researchers have increasingly begun to study other animals, as in a recent paper that focused on grizzly bears. During the months leading up to hibernation, they are capable of doubling their levels of body fat. Such massive weight gain would result in serious health problems for humans, but bears are capable of tolerating these fluctuations, leading the authors to investigate how exactly this was possible.
So what’s their secret? As it turns out, bears are capable of uniquely regulating a protein called PTEN (phosphatase and tensin homolog), which has a role in shutting off insulin signaling (among other things). During the fall, while bears are bulking up, they turn off PTEN, which results in increased insulin sensitivity and stable blood sugar levels despite weight gain. While hibernating, PTEN is turned back on, making the bears more insulin resistant and slowing weight loss during their long winter snooze. These findings with PTEN actually mirror a previous study in humans, in which patients who only had one copy of PTEN instead of two were more resistant to complications associated with weight gain, namely diabetes and heart disease.
So all we have to do is turn off PTEN in people and their type 2 diabetes will go away, right? Unfortunately, it’s not quite that simple. Remember how PTEN does more than simply shutting down insulin signaling? Well, one of those things is kind of important: It prevents cancer. PTEN is an essential tumor suppressor that has been implicated in dozens of malignancies. Indeed, those patients who lacked one copy of PTEN were found to develop aggressive cancers at a much higher rate than normal. Though this may be potentially circumvented by targeting PTEN in fat cells only, it is still obviously a major concern for therapeutic development.
There’s an additional drawback to this sort of treatment as well. While diabetes is certainly a cause of reduced quality of life, making patients more insulin sensitive will also result in increased weight gain. It’s likely that turning off PTEN would improve the metabolic profile of a patient, but may have unintended side effects of exacerbating arthritis and joint or back pain.
Since the obesity epidemic shows no signs of slacking, addressing the associated comorbidities is a major priority for biomedical researchers. And while this research is certainly promising, there are significant barriers that need to be overcome before a drug can even begin to be conceptualized. So no, we haven’t found the cure for diabetes in bears, and if we had, it would have the pretty nasty side effect of causing cancer.