Progress Reported in Developing Compounds That Mimic Insulin for the Treatment of Type II Diabetes


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Diabetic patients suffer from a metabolic disorder in which the insulin hormone responsible for allowing the passage of energy rich nutrients from the bloodstream into the body's cells does not function properly or at all. Diabetes afflicts 15 million Americans, and 90 percent of these cases are classified as type II diabetes.
Type I diabetes is caused by a shortage of insulin production from cells in the pancreas. Type II diabetes is the result mainly of resistance or insensitivity of cells to insulin activity. One of the approaches to treating type II diabetes is to find a new chemical that will serve as a viable alternative to insulin and thus will not be affected by problems of insulin resistance. Weizmann Institute scientists have recently made significant progress in this area, which may one day lead to the development of a treatment that will considerably improve the quality of life of those suffering from type II diabetes.
Some two decades ago, Prof. Yoram Shechter of the Institute's Biological Chemistry Department was one of the first scientists to discover that vanadium, a metallic trace element, mimics most of the metabolic effects of insulin in tissue studies. When given to diabetic rodents, vanadium corrects many metabolic defects associated with diabetes, in which insulin is lacking or is not functioning properly.

Since that discovery, scientists at the Institute and elsewhere have conducted intensive studies aimed at utilizing vanadium in the treatment of diabetes, as an artificial substitute for insulin. Such treatment would have two major advantages. First, unlike insulin, which needs to be injected into the bloodstream, vanadium can be given in the form of pills. Second, on the molecular level, vanadium's mechanism of action is largely different from that of insulin. This makes vanadium particularly valuable in the treatment of cases in which insulin is ineffective.

The use of vanadium as a substitute for insulin, however, has been stymied until now by the fact that vanadium, like many other metal ions, is toxic in the high concentrations that must be used to make it effective. The goal of vanadium-related research in diabetes has been to develop vanadium-based compounds that are less toxic and, if possible, have greater antidiabetic potency than vanadium itself.

Now, a team of Institute scientists including Shechter, Prof. Mati Fridkin of the Organic Chemistry Department and graduate student Itzhak Goldwaser has managed to achieve just that. After checking hundreds of chemicals, they have found one family of amino acid analogues that, when forming a complex with vanadium, are three to four times more effective than vanadium alone in mimicking the effects of insulin.

In a study reported in the current issue of the Journal of Biological Chemistry, the Institute scientists showed that the new compounds - patented through Yeda Research and Development Co. Ltd., which deals with the commercialization of the Institute's research - are effective in regulating glucose levels in diabetic laboratory animals while given in small amounts. These substances are being developed for clinical use by a start-up company, LAPID Pharmaceuticals Ltd., created recently by Pamot Venture Capital Fund and Yeda. Further animal studies must be conducted to show whether the compounds are appropriate for application in humans.

Prof. Shechter holds the Charles H. Hollenberg Chair of Diabetes and Metabolic Research, and Prof. Fridkin, the Lester B. Pearson Chair of Protein Research.

The Weizmann Institute of Science, in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. Its 2,500 scientists, students, technicians, and engineers pursue basic research in the quest for knowledge and the enhancement of humanity. New ways of fighting disease and hunger, protecting the environment, and harnessing alternative sources of energy are high priorities at Weizmann.

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