One of the hottest properties in biotechnology - a potential drug to treat obesity - may have encountered a stumbling block. A protein that makes obese mice lose weight also interferes with insulin in cultured human liver cells, according to a report in the November issue 15 Science . The results suggest that diabetes may be a potential side effect of a drug based on leptin.
In December 1994, scientists at Rockefeller University announced they had discovered a human gene similar to that which, when mutated, causes severe hereditary obesity in mice. Normal genes codes for a protein called leptin, and the discovery suggests that leptin plays a crucial role in regulating weight. The prospect of a powerful weight loss drug has triggered a bidding war between biotechnology companies. The winner, biotech giant Amgen Corp. Thousand Oaks, California, paid a whopping $ 20 million for exclusive rights to the patent Rockefeller to develop products based on leptin.
But now comes what may be a reality check of a team at the Weizmann Institute in Rehovot, Israel. They found that the protein interferes with the normal function of insulin receptors in human liver cells in culture (see diagram). the function of the receptor reduced in people heralding the onset of adult diabetes.
Experts are struggling to interpret the results, however, because they conflict with previous work showing that too little leptin may trigger the same effect in liver cells. It could be that leptin levels outside a relatively narrow range - too high or too low - are harmful to the cells, says Jeffrey Flier, an endocrinologist at Beth Israel Deaconess Medical Center, Boston. Or, Flier said, it may simply be that the Weizmann study found "a biochemical artifact of some sort."
Other scientists agree that the findings of the test tube may not reflect how tissues and organs all respond to leptin. "It's a big jump to go from the cellular tissue situation to the human situation," says Simeon Taylor, a researcher Diabetes National Institutes of Health. Geneticist Weizmann Menachem Rubinstein urges researchers to pursue long-term animal studies leptin, which could signal the cumulative effects in people.
0 Komentar