FAT-FIGHTING PROTEIN TIED TO DIABETES IN ISRAELI TESTS.

Byline: Associated Press 

A natural protein that some hoped would be a ``magic bullet'' for weight control may have a dark and dangerous side. New research links the compound with diabetes.

The protein, called leptin, received a flurry of publicity last year when studies showed that it caused extremely obese mice to lose up to 30 percent of their weight. The mice also exercised more and ate less. Some researchers raced to develop leptin or related proteins for use in humans.

But now a lab in Israel has found that leptin may play a role in development of Type II diabetes, a serious disorder that frequently strikes obese adults.

Menachem Rubinstein, a biochemist at the Weizmann Institute of Science in Rehovot, Israel, said that when leptin is put on human liver cells in the laboratory, it disrupts a normal action of insulin, the hormone essential for control of sugar in the blood.

``We know that obese individuals have a high level of leptin and we know that obese individuals have a tendency to develop diabetes,'' Rubinstein said in an interview. ``There might be a linkage. It might be that leptin is one of the agents that induces Type II diabetes.''

He said clinical studies with leptin should be approached with caution.

``One should look very carefully into using leptin as a weight-reducing agent,'' Rubinstein said. ``It should be ruled out that a long-term treatment with leptin doesn't induce Type II diabetes.''

Amgen Inc. of Thousand Oaks, a biotechnology firm, started human clinical trials with leptin in May to determine if the protein causes any toxic side effects. The firm plans clinical studies next year to determine if leptin actually will control weight.

David Kaye, a spokesman for Amgen, said that so far researchers for the company have detected no harmful side effects from leptin.

Rubinstein said his laboratory experiments showed that leptin will link up with liver cells and interrupt a series of chemical reactions that normally are directed by insulin.

Insulin is produced by the pancreas and has two basic functions. It works in the blood to break down glucose, a type of sugar, into glycogen and fat. It also works in the liver to control the conversion of stored fat back into glucose, a process called gluconeogenesis.

Leptin, Rubinstein said, interrupts the gluconeogenesis function of insulin. This could cause blood sugar levels to rise inappropriately, he said.

Rubinstein emphasized that his experiment involved only cell cultures and that leptin could react differently in the body.

``The experiment would have to be repeated in whole animals, because there are many systems that can counteract or compensate events that occur in individual cells,'' he said.