NEW YORK, Dec. 12 (UPI) -- A protein found in human fat cells may become key to the development of future treatments for type-2 or adult onset diabetes, researchers reported Wednesday.
"There are molecules produced by the fat cells, the adipose tissue, circulating throughout the body and affecting the functions of different organs," said Dr. Luciano Rossetti, senior author and professor of medicine at the Albert Einstein College of Medicine in New York City. "Our research identifies one very important protein, Acpr30, that is made in fat cells--- and made less abundantly in the fat cells of obese people and
animals -- that significantly affects insulin action in the liver."
Type-2 diabetes affects between 6 million and 8 million Americans and is rising in epidemic proportions as obesity rates also rise. Type-2 diabetes accounts for 90 percent to 95 percent of all diabetes cases.
"The majority of people who have type-2 diabetes are obese, about 80 to 90 percent," Rossetti said. "The idea has been developed that the adipose cell where the fat is stored is also producing very active molecules that are really functioning as hormones."
He said his research team found a very clear mechanism by which an increase or decrease in fat cell size, as happens in obese humans, might cause severe hepatic (liver) insulin resistance because less of a hormone-like protein, Acrp30, is secreted by the fat cell.
The researchers used a genetic approach in cells to generate an exact copy of the Acrp30 protein. They injected mice with Acrp30 until they doubled the protein level.
"We asked the question, 'If we simply doubled the concentration of this adipose-derived hormone and then carefully measure the hepatic glucose production -- or action of insulin on the liver-- are we generating a significant effect?' The answer we found was a clear-cut'Yes,'" Rossetti said. "What's really interesting about Acrp30 is that we know that it is missing or lower in obese people."
He said the study suggests just small increases have a major effect in decreasing glucose production in the liver and thereby improving insulin action in the liver.
"This significant research points to the liver as the key sight of action by Acpr30," said Dr. Allen Cherrington, professor of physiology at Vanderbilt University Medical School in Nashville. "It could be one key in helping us find new ways to lower glucose profiles in type-2 diabetics and slow the development of disease."
Acrp30 is a very large protein and it can only be given by injection.
"The future of this biological discovery is in identifying either the receptor for the protein, in other words how it is working in the liver, and then creating a smaller molecule that will mimic the effect of Acrp30 or perhaps finding a way to stimulate the secretion of Acrp30 within the fat cell," Rossetti said.
"Either of these strategies will be targets of companies trying to develop drugs from this kind of research."
He said in the United States there is a special need to find a biological approach to the treatment of obesity-related diabetes, since aging Americans often are unable to lose weight effectively.
"It is a matter of dissociating the insulin resistance that causes diabetes from obesity per se," he said. "The story of our research heads in that direction."
The research is published in the December issue of The Journal of Clinical Investigation.
(Reported by Bruce Sylvester in West Palm Beach, Fla.)
