Obesity linked to type 2 diabetes by an absent protein


Obese people have a higher risk for developing type 2 diabetes, a condition where the body loses its ability to control glucose. And, while the link between obesity and type 2 diabetes is statistically evident, biological explanations are less so. Now scientists have discovered that a key protein that helps the body control glucose, is missing in obese people.

The team, from the Institute of Molecular and Cell Biology, one of the research institutes of the Agency for Science, Technology and Research in Singapore, reports its findings in the journal Cell Reports.

Obesity is a common, serious condition that increases risk of stroke, heart disease, type 2 diabetes and certain types of cancer, some of the leading causes of preventable deaths.

According to the Centers for Disease Control and Prevention, obesity now affects more than a third of adults in the US, where the cost of the condition was estimated to be $147 billion in 2008.

Once considered a problem only in the more wealthy countries, overweight and obesity are now rising rapidly in low and middle-income countries, particularly in urban settings.

Type 2 diabetes develops when the body does not make enough insulin to help it control glucose or the body’s cells become resistant to insulin. The result is high levels of glucose in the blood, which if untreated, leads to more serious conditions like blindness, cardiovascular disease, loss of limbs, and kidney failure.

More than 360 million people around the world have type 2 diabetes, including about 8% of Americans. The World Health Organization projects that diabetes will be the 7th leading cause of death worldwide in 2030.

NUCKS protein regulates insulin signaling in cells

In their investigation, the IMCB team discovered that a protein called NUCKS is an important regulator of insulin signaling in cells. They showed that endocrine cells lacking the ability to make the protein had impaired insulin signaling.

Also, mice bred to lack NUCKS showed “decreased insulin signaling and increased body weight/fat mass along with impaired glucose tolerance and reduced insulin sensitivity, all of which are further exacerbated by a high-fat diet,” note the authors.

They also found that NUCKS is downregulated – that is the genes that code for the protein are more or less inactive – in obese individuals. It was also found to be downregulated in mice raised on a high fat diet, yet levels of NUCKS went up upon starvation.

The researchers suggest obese individuals who lack NUCKS develop insulin resistance and lose the ability to regulate their glucose effectively, leading them to have high levels of it in their blood, which makes them more vulnerable to type 2 diabetes.

First discovery of a direct molecular link between obesity and type 2 diabetes

They say this is the first time a direct molecular link has been discovered between obesity and type 2 diabetes, and will lead to new research projects to identify drugs and lifestyle changes that can restore NUCKS to normal levels in the body.

Study leader Dr. Vinay Tergaonkar, Principal Investigator at IMCB, says:

“Every year, billions of dollars are spent on metabolic diseases and a big part of the expenditure goes to the drugs for diabetes. The findings in our study have immense therapeutic implications as they will be applicable not only to diabetes in obesity, but also to diabetes as a whole.”

Meanwhile, Medical News Today recently reported how a team from the University of California, San Diego in the US discovered that a biological link between obesity and type 2 diabetes may also explain how obesity can lead to cancer. The researchers showed that the protein HIF-1 alpha played a key role in the development of insulin resistance and type 2 diabetes in obese mice. They also showed that the protein helps tumor cells to survive conditions of low oxygen.

Written by Catharine Paddock PhD



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