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Molecular Link between Obesity And Diabetes Found

Last Updated: 2005-07-20 15:55:24 -0400 (Reuters Health) LONDON (Reuters)

Scientists have discovered a molecular link between obesity and type 2 diabetes that could be a potential target for new drugs to treat the disease.

They found that a protein released by fat tissue in mice causes insulin resistance, a primary risk factor for diabetes. Elevated levels of the protein had
also previously been detected in patients with diabetes.

"Being resistant to insulin is one of the major causes of diabetes," said Dr Barbara Kahn of Beth Israel Deaconess medical Center in Boston, Massachusetts,
and the lead author of the research published in the science journal Nature.

"And in the absence of diabetes, insulin resistance is a major risk factor for heart disease and early mortality."

Insulin, which is produced by the pancreas, regulates blood sugar levels. People with type 1 diabetes, which accounts for 10-25 percent of cases, do not produce any insulin,
which helps glucose, or sugar, from food get into cells.

Type 2 diabetes, the most common form of the disease, is caused by an inability to make enough, or to properly use, insulin. About 90 percent of diabetes sufferers have type 2, which is linked to being overweight or obese.

The scientists found the protein, called retinol binding protein (RBP4), by studying mice that had been genetically engineered to overproduce or underproduce another protein linked to insulin

They also discovered that increasing levels of RBP4 caused insulin resistance while decreasing levels relieved the condition.

In people who are obese or suffer from type 2 diabetes, excess amounts of RBP4 are linked to the severity of insulin resistance.

"There is a rapidly increasing epidemic of obesity and type 2 diabetes in the western world," said Khan.

"It is, therefore, clear that more effective treatment strategies are needed to prevent and treat diabetes. RBP4 could prove to be a novel target for developing anti-diabetic therapies," she added.

Gene Is Linked with Obesity And Diabetes

WASHINGTON (Reuters) - A gene that may regulate the body's response to insulin has been linked to both obesity and type-2 diabetes, researchers in Britain and France reported Monday.

The discovery helps explain how being overweight is associated with type-2 or adult-onset diabetes, the researchers report in this week's issue of the journal Nature Genetics.

It may also some day offer new ways to treat the conditions, both of which are on the rapid rise across the world.

"Although this discovery is not going to lead to a 'magic pill' for curing obesity and type-2 diabetes, it could help in identifying groups and individuals at increased risk," said Philippe Froguel, who led the team at Imperial College London, Institut Pasteur de Lille in France and other institutions.

"If we can identify those at risk at an earlier age, it may be possible to take preventive measures earlier on, and reduce the burden of ill health caused by obesity in later life," he said.

Froguel and colleagues started with 62 families prone to both obesity and diabetes. They found a gene called ENPP1 that seemed to be similar among the families.

Then they cast their net widely across northern Europe, looking at more than 4,000 people, obese and not.

They found 11 different variations of the gene, called single nucleotide polymorphisms or SNPs. Six of these forms were linked with severe obesity.

The gene helps control how cells respond to insulin, which in turns helps them use glucose efficiently.

In people with diabetes, cells do not use insulin correctly and their blood gets filled with too much glucose.

Type-2 diabetes usually does not occur suddenly, but develops over time, beginning with a condition called insulin resistance. People who are obese or overweight are much more likely to have insulin resistance, but it is not entirely clear which comes first - the obesity or the insulin resistance.

In the children in Froguel's study, more ENPP1 seemed to mimic the effects of insulin resistance in the brain, where insulin suppresses appetite.

So it may be that this particular form of the gene interferes with both appetite and the ability to use insulin correctly, Froguel's team suggested.

"The identification of ENPP1 as a molecular mechanism for obesity and diabetes means we may be able to use it as a target to develop new therapies and treatments, ultimately leading to more effective ways of treating diabetes," Froguel said.

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