Research team identifies link between inflammation and type 2 diabetes

February 5, 2015, Yale University

A Yale-led research team has identified the molecular mechanism by which insulin normally inhibits production of glucose by the liver and why this process stops working in patients with type 2 diabetes, leading to hyperglycemia.

The findings are published Feb. 5 in the journal Cell.

"In the study, we set out to examine how insulin normally works to turn off production of glucose by the and why this process goes awry in patients with type 2 diabetes," said Gerald I. Shulman, the George R. Cowgill professor of physiological chemistry, professor of medicine and cellular & molecular physiology at Yale School of Medicine, and an investigator with the Howard Hughes Medical Institute.

Experts have long debated how insulin suppresses glucose production by the liver. Many have asserted that insulin's suppression of glucose production was due to the direct action of insulin on the liver. But the Yale-led team uncovered a different process that challenges current theories and may lead to new targets for treatment.

Yale researchers hypothesized that insulin suppressed glucose production by the liver by inhibiting the breakdown of fat, which would result in a reduction in hepatic acetyl CoA, a key molecule that they showed was critical in regulating the conversion of amino acids and lactate to glucose. They also found that reversal of this process, due to inflammation in adipose (fatty) tissue, led to increased hepatic production and hyperglycemia in high-fat-fed rodents and obese, insulin-resistant adolescents. "These studies identify hepatic acetyl CoA as a key mediator of insulin action on the liver and link it to inflammation-induced hepatic insulin resistance and type 2 diabetes," Shulman explained.

This new insight into insulin resistance paves the way for exploring new treatments. "None of the drugs we currently use to treat type 2 target the root cause," said Shulman. "By understanding the molecular basis for hepatic resistance we now can design better and more effective drugs for its treatment."

Explore further: Diabetes debate: Triglycerides form in liver despite insulin resistance

More information: Cell DOI: 10.1016/j.cell.2015.01.012

Related Stories

Diabetes debate: Triglycerides form in liver despite insulin resistance

January 5, 2015
Solving one of the great mysteries of type 2 diabetes, a team of Yale researchers found that triglycerides, a type of fat in the blood and liver, are produced in the liver independent of insulin action in the liver.

Protein linked to aging identified as new target for controlling diabetes

November 5, 2014
Indiana University School of Medicine researchers have identified a small protein with a big role in lowering plasma glucose and increasing insulin sensitivity. Their research appeared online today in Diabetes, the journal ...

How does DPP-4 inhibition affect liver function?

January 27, 2015
(HealthDay)—Dipeptidyl peptidase-4 (DPP-4) inhibition may attenuate hepatic steatosis and insulin resistance induced by the Western diet (WD) through hepatic lipid remodeling and modulation of hepatic mitochondrial function, ...

How leptin, the 'satiety hormone,' reverses diabetes

June 16, 2014
(Medical Xpress)—Treatment with leptin, the hormone associated with fullness or satiety, reverses hyperglycemia in animals models of poorly controlled type 1 (T1D) and type 2 (T2D) diabetes by suppressing the neuroendocrine ...

Reversing key precursors to diabetes

November 6, 2013
Yale researchers have found a way to disrupt the biological underpinnings of disorders that predispose a person to type 2 diabetes (T2D), raising the possibility of developing therapies to reverse these conditions. The study ...

Estrogen may improve pathway-selective insulin resistance

February 14, 2013
(HealthDay)—Estrogen treatment at the time of surgical menopause may reverse aspects of pathway-selective insulin resistance in the liver associated with a high-fat diet (HFD) in mice by promoting insulin action on glucose ...

Recommended for you

Gene plays critical role in noise-induced deafness

October 19, 2018
In experiments using mice, a team of UC San Francisco researchers has discovered a gene that plays an essential role in noise-induced deafness. Remarkably, by administering an experimental chemical—identified in a separate ...

Scientists grow functioning human neural networks in 3-D from stem cells

October 18, 2018
A team of Tufts University-led researchers has developed three-dimensional (3-D) human tissue culture models for the central nervous system that mimic structural and functional features of the brain and demonstrate neural ...

Functional engineered oesophagus could pave way for clinical trials 

October 18, 2018
The world's first functional oesophagus engineered from stem cells has been grown and successfully transplanted into mice, as part of a pioneering new study led by UCL.

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

0 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.