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- Global epidemiology of prediabetes - present and future perspectives. - Abstract - Europe PMC
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.
This state is referred to as insulin resistance, and it is considered to be a major contributor can high blood sugar cause increased heart rate the further development of type 2 diabetes. A major problem encountered by scientists seeking to study obesity and diabetes is that treatments can high blood sugar cause increased heart rate 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.
As it turns out, bears are capable of uniquely regulating a protein called PTEN phosphatase and tensin homologwhich 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?
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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.
- Wake Forest Baptist Medical Center Summary: Bradycardia -- a slower than normal heartbeat -- does not increase the risk of developing cardiovascular disease, according to a study.
- Slow heart rate does not increase risk of heart disease -- ScienceDaily
Though this may be potentially circumvented by targeting PTEN in fat cells only, it is still obviously a major concern for therapeutic development. While diabetes is certainly a cause of reduced quality of life, making patients more insulin sensitive will also result in increased weight gain.
Since the obesity epidemic shows no signs of slackingaddressing 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.