Possible "root cause" of Type 2 Diabetes found

In MedicalExpress News: ( http://medicalxpress.com/news/2016-02-diabetes-discovery-effective-drugs.html ):

** Diabetes discovery could lead to more effective drugs**

The formation of type 2 diabetes is directly related to how our muscles convert sugar, a landmark new study has found.
Researchers at the University of Melbourne’s Medical School at the Austin Hospital have used elegant gene splicing technology to prove this popular theory about the biological cause of Type 2 diabetes.

The work, published in Molecular Metabolism, is the first strong evidence that when muscles fail to convert glucose into a substance called glycogen, it leads to the hallmarks of type 2 diabetes.They hope the research will lead to development of a drug to that could convert glucose into glycogen when muscle metabolism fails.

Chronic high glucose levels are associated with stroke, kidney failure, blindness and leg amputations. Most patients with diabetes die from heart attack or stroke. Yet researchers still know very little about the biological processes that lead to this condition. Lead researcher on the project, University of Melbourne Associate Professor Sof Andrikopoulos, said the finding gives researchers a much better idea of where to target treatments for type 2 diabetes.

“We’ve known for decades the inability of muscle and fat to respond to insulin (known as insulin resistance) is a major mechanism that leads to high glucose levels in type 2 diabetes,” Assoc Prof Andrikopoulos
said. “If you have insulin resistance, the sugar stays in your bloodstream. So the inability of the muscle to
transport sugar into the muscle cell is what leads to higher blood sugar levels.”

The researchers tested the theory with sophisticated gene technology. They effectively deleted the enzyme that makes glycogen from glucose from the muscle and watched what occurred. "None of the drugs available at the moment treat the underlying cause of the disease. "This provides us with more information about which pathways we should target to treat diabetes. Currently, we don’t have any drugs that target this pathway.

“The study also explains why one of the reasons patients with diabetes don’t exercise properly is that they may not have glycogen – if you improve your glycogen stores, you improve the ability to exercise.” Diabetes is linked to cardiovascular disease, hypertension, stroke, mental illnesses and blindness. Currently, 1.7 million people live with
diabetes. At the Austin, about one in three patients over 55 have diabetes.

More information:
Chrysovalantou E. Xirouchaki et al. Impaired glucose metabolism and exercise capacity with
muscle-specific glycogen synthase 1 (gys1) deletion in adult mice, Molecular Metabolism (2016). DOI: 10.1016/j.molmet.2016.01.004

2 Likes

this is something, i find, to be, very interested, in,.

thanks for the link.

Thanks for sharing this, @Thas! We tend to hear so little about research into the actual causes of type 2, despite all we hear about the risk factors. It’s refreshing to get some science on the issue!

This is interesting, @Thas . I wonder if this will gain traction and credibility as peers around the world review it. Let’s hope it leads to an effective treatment that will help a whole lot of people.

Great article! Thanks, Thas!

So IOW, the mechanism that leads to the full blown expression of T2D isn’t the lack of exercise, it’s the inability to exercise?

We should always take these “press announcements” with a grain of salt. There are already more than 20 genes associated with T2. While the researchers may have found a gene that “can cause T2” it hardly explains T2 let alone suggests a cure.

Very interesting. So a person can have sufficient skeletal muscle for glucose uptake but still have type2 diabetes because the muscle can’t convert glucose to glycogen. Interesting. Makes me wonder if that is the case would insulin take up the slack?

This study was undertaken in mice. What is interesting is that this would mean is that there would need to be dysfunction in the Krebs cycle of humans. I am no biochemist but from what I understand about human physiology carbohydrates are the main fuel the body uses to create ATP. If the human body can not create, ATP then there is no muscle contraction. No heart beat, no, digestion, no nothing. DEATH.

There’s no IRB in the whole entire world that would approve this study on humans. To remove an enzyme that is part of the TCA cycle. Seems dubious. And I’ve never heard of any case of any human or animal being unable to produce ATP.

This study is started to sound like a PhD (piled high and deep).