Diabetes - Finding the Cause

Role of new hormone called resistin may explain the cause of type 2 diabetes.

BALTIMORE, Maryland (AP) -- Scientists have discovered a hormone that may explain the link between diabetes and obesity -- a tantalizing finding that could someday lead to new treatments for the disease.

The hormone, dubbed resistin, is produced by fat cells and prompts tissues to resist insulin, the substance the body needs to process blood sugar, researchers reported in Thursday's issue of the journal Nature.

Diabetics produce too little insulin or cannot use it efficiently.

"I don't think it's an exaggeration to say this is a blockbuster paper with potentially major clinical impact," said Dr. Allen Spiegel, director of the National Institute of Diabetes and Digestive and Kidney Diseases, a division of the National Institutes of Health, which funded the research.

Obesity is one of the biggest risk factors for Type II, or adult-onset, diabetes. The adult-onset form of the disease accounts for more than 90 percent of all cases of diabetes.

The University of Pennsylvania scientists identified resistin in mice and found genetic evidence that the same hormone exists in humans, though they have yet to isolate it.

Mice given resistin were not able to process blood sugar as well as those that were not given the hormone. And mice given a drug that lowers resistin levels were better able to process blood sugar and use insulin.

Adult-onset diabetes is blamed on obesity, aging and a sedentary lifestyle. Nearly 6 percent of Americans suffer from diabetes, a major cause of blindness, kidney disease, amputations and death.

While synthetic insulin is often used to treat diabetes, researcher Mitchell A. Lazar compared its use to talking louder to deal with a poor telephone connection rather than fixing the line.

A new class of drugs called TZDs that make the body use insulin more effectively prompted the researchers to search for the hormone. The researchers hypothesized that the drug might be targeting a hormone.

They looked at which genes were activated or deactivated by the TZD. From there, they zeroed in on the hormone.

"It was kind of like panning for gold," said Lazar, director of the university's Diabetes Center. "When you compared what was turned on and off in both of the cells you were left with those few nuggets."

Why the cells make resistin is not known, but it may be related to the helping the body deal with periods of famine, Lazar said.

Resistin "may form at least part of the missing link between obesity and diabetes," Jeffrey S. Flier of the Beth Israel Deaconess Medical Center in Boston said in an accompanying editorial.

The exact role of the hormone, however, is not known, and how differences in the ability to produce the hormone affects diabetes needs to be determined, Flier said.

Morris White, a researcher at the Joslin Diabetes Center at Harvard Medical School, cautioned that the finding is intriguing, but the connection had not been proved.

"This is sort of circumstantial evidence that, yes, this is a hormone and it has a function," White said. "There's no proof it's actually working at the liver or at the fat cell or the muscle cell to change the blood glucose. You don't really know how it works."

If resistin is a key player, it could allow for more specifically targeted drugs, said Ed Leiter, a diabetes research at Jackson Laboratories in Bar Harbor, Maine, who was not involved in the research.

"If you can find drugs that primarily block the resistin gene from turning on, or expressing, you can tailor your drug," Leiter said. TZDs have a more scattershot approach, he said.

Leiter compared the work to the 1994 discovery of leptin, a hormone also made by fat cells that helps the brain control eating. Leptin has prompted research into eating disorders, obesity and diabetes.

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