Protein Could Lead to New Diabetes Drugs

[jabialaa]

THURSDAY, July 21 (HealthDay News) -- A protein that's overproduced by fat cells in obese individuals appears to promote insulin resistance -- elevating the risk for diabetes, heart disease and early death, according to researchers.
Until now the particular protein -- known as retinol binding protein 4, or RBP4 -- had been known solely for its innocuous role as a "transport vehicle," involved in the delivering of vitamin A to healthy tissue.
Identifying RBP4's less benign function as an instigator of insulin resistance may lead doctors towards new drug interventions that focus on limiting secretion of the protein among obese patients at risk for type 2 diabetes.
"We have found a molecule not previously known to have any role in insulin action and demonstrated that this protein can contribute to the development of diabetes by blocking the action of insulin," said study co-author Dr. Barbara B. Kahn, chief of the division of endocrinology, diabetes, and metabolism at Beth Israel Deaconess Medical Center in Boston.
Type 2 diabetes develops as the result of insulin resistance, a condition defined by the body's inability to properly utilize naturally produced insulin for the breakdown of sugars, starch and other glucose-rich foods into energy. The resulting dangerous buildup of glucose and insulin in the blood is also associated with a high risk for cardiovascular disease.
According to American Diabetes Association estimates, more than 18 million Americans have diabetes. Approximately 90 percent of these patients have type 2 diabetes, while the remainder are afflicted with type 1 diabetes -- a distinct version which results from the body's inability to produce insulin altogether.
Noting that insulin resistance seems to go hand-in-hand with reduced levels of the glucose transporter protein, the researchers used specially bred mice to look for a causal relationship between levels of RBP4 and other fat-cell proteins.
After eliminating a range of alternate molecular options, they observed that levels of glucose-carrying proteins fell as fat cell RBP4 production rose.
Further tests in both mice and humans confirmed that excess production of RBP4 appears to promote a drop in the glucose-carrying proteins.
Insulin resistance, they concluded, might therefore be avoided if RBP4 levels could be reduced and controlled. Kahn's team reported the findings in the July 21 issue of Nature.
"This opens up a whole new treatment possibility for preventing or treating type 2 diabetes, and for stopping the progression from obesity to diabetes," said Kahn.
Cathy Nonas, director of the obesity and diabetes program at North General Hospital in New York City and spokeswoman for the American Dietetic Association, expressed enthusiasm for any research that might lead to new drug targets. But she cautioned that the best treatment for diabetes is prevention.
"We all hope that with this research they might be able to manage diabetes better and maybe even prevent diabetes from occurring as a result of insulin resistance," said Nonas. "But I think Kahn would agree that no matter what we do, nothing will get around the need to change our environment and change our lifestyle. It is very important to understand diabetes. But we also need to keep our weight at a healthy level. That's probably the best medicine of all."
Nonas emphasized that many U.S. adults and adolescents eat, drink and sit around too much -- ignoring the need for routine exercise and healthy diets.
"Nothing can replace the need to prevent obesity in the first place," she said. "Obesity is one of the major precursors of insulin-resistance. So the need to have more physical activity and manage weight is something that doesn't go away no matter what new treatments unfold."
Kahn suggested, however, that while lifestyle is always at the heart of any battle against obesity and diabetes, it is equally important to keep up the search for new treatment targets such as RBP4.
"I agree that drugs don't take the place of diet and exercise," said Kahn. "But unfortunately there are also some genetic underlying causes related to diabetes. There are many people in the world who have type 2 diabetes who are not obese. So we will also need treatments in combination with diet and exercise to make everyone healthy."

[saricloud]

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[jabialaa]

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[Andria]

A protein that's overproduced by fat cells in obese individuals appears to promote insulin resistance -- elevating the risk for diabetes, heart disease and early death, according to researchers.

The particular protein -- known as retinol binding protein 4, or RBP4 -- had been known solely for its innocuous role as a "transport vehicle," involved in the delivering of vitamin A to healthy tissue.

Identifying RBP4's less benign function as an instigator of insulin resistance may lead doctors towards new drug interventions that focus on limiting secretion of the protein among obese patients at risk for type 2 diabetes.



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