Protein may play role in obesity, diabetes, aging

By Michael C. Purdy

(Medical Xpress) -- Researchers at Washington University School of Medicine in St. Louis have identified a potent regulator of sensitivity to insulin, the hormone that controls blood sugar levels. The new findings may help scientists find better treatments for type 2 diabetes, obesity and other health problems caused by the body’s inability to properly regulate blood sugar.
 
The research is published online Feb. 13 in PLoS ONE.

Fat and muscle in patients with become resistant to insulin, which normally causes them to take in glucose from the blood. The protein studied by the researchers, known as TBC1D3, keeps the insulin pathway open, so the cells can continue to take up glucose. TBC1D3 is found only in humans and certain other primates.

“When cells made more of the TBC1D3 protein, they had a much bigger response to insulin,” says senior author Philip Stahl, PhD, professor of cell biology and physiology. “We found that TBC1D3 significantly slows the deactivation of a molecule that relays signals from the insulin receptor. This enhances the cells’ response to insulin.”

Stahl studies G proteins, which help convert signals from hormones like insulin into specific actions within cells. He became interested in TBC1D3 because part of it binds to some G proteins.

In the new study, Stahl and his colleagues showed that higher levels of TBC1D3 impede a feedback loop that normally deactivates the insulin signal into the cell from receptors on the cell membrane.

“There are quite a few regulatory pathways like this in biology,” Stahl says. “To make sure the signal doesn’t stay on indefinitely, there are factors built into the signaling pathway that reach back to the origin of the signal and attempt to shut it off.”

More active TBC1D3 impedes that feedback process, keeping the insulin signaling pathway turned on longer, Stahl explains.

Stahl and his colleagues tracked the effects of TBC1D3 to a cluster of proteins that control some of the cell’s most important functions, including nutrient uptake, cell growth and proliferation, and aging.

“We found that TBC1D3 activates a protein called PP2A,” Stahl says. “Flies had shorter lifespans when the PP2A gene was knocked out. This suggests that TBC1D3 also may influence the aging process.”

The researchers are now investigating the factors that regulate the activity of TBC1D3. One such influence may be the number of copies of the TBC1D3 gene in a person’s DNA.

TBC1D3 is one of the most duplicated genes in humans, appearing anywhere from five to more than 50 times in an individual’s DNA. The scientists plan to compare cells with many copies of the gene to others with fewer copies to see whether the number of copies is linked to changes in the cells’ response to .

More information: Wainszelbaum MJ, Liu J, Kong C, Srikanth P, Samovski D, Su X, Stahl PD. TBC1D3, a hominoid-specific gene, delays IRS-1 degradation and promotes insulin signaling by modulating p70 S6 kinase activity. PLoS ONE, online Feb. 13, 2012.

Related Stories

It takes a sugar to catch a sugar

date Dec 02, 2011

After every meal, the hormone insulin is released into the bloodstream, issuing instructions to target cells to begin taking up excess sugar. In some situations, however, cells stop responding to these signals; ...

Pig to primate transplants show promise for diabetes

date Nov 09, 2011

(Medical Xpress) -- Scientists exploring a potential cure for diabetes have shown that transplanting insulin-producing cells from embryonic pigs into diabetic monkeys can dramatically lower blood sugar levels, ...

Unearthing a path leading to diabetes

date Jan 06, 2012

A molecular mechanism that links diet, obesity and diabetes involves depletion of specialized ‘transporter proteins’, a Japanese–American team has found. Transporter proteins deliver glucose ...

Recommended for you

Faster heart rate linked to diabetes risk

date 7 hours ago

An association between resting heart rate and diabetes suggests that heart rate measures could identify individuals with a higher future risk of diabetes, according to an international team of researchers.

EBV co-infection may boost malaria mortality in childhood

date 22 hours ago

Many people who live in sub-Saharan Africa develop a natural immunity to malaria, through repeated exposure to Plasmodium parasites. Even so, the disease kills close to half a million children per year, according ...

Three important things you didn't know about diabetes

date May 21, 2015

When we think of diabetes, we tend to think of rich people with poor lifestyles. A chronic disease linked with obesity, heart disease and worse outcomes for some infectious diseases, diabetes tends to be ...

Changes observed in HbA1c during ramadan

date May 20, 2015

(HealthDay)—For patients with type 2 diabetes, during Ramadan, the greatest change among metabolic parameters is seen for glycemia, according to a study published online May 13 in the Journal of Diabetes In ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.