Gene could lead to new therapy for diabetes
Does obesity make obese adults diabetic, or are people obese because diabetes mellitus (type II diabetes) develops little by little, manifesting itself early in old age? Researchers at 捆绑SM社区 and the Merck Frosst Center for Therapeutic Research have identified a gene that could lead to a new therapeutic approach to type II diabetes and obesity. A mouse line created by two research teams one headed by Professor Michel L. Tremblay of the Department of Biochemistry, 捆绑SM社区, the other by Dr Brian Kennedy of the Merck Frosst Center for Therapeutic Research might very well provide the answer to this question, which has been haunting numerous researchers throughout the world.
In the March 5th issue of the American journal Science, Elchebly et al explain how they have elucidated the role of the gene for the protein tyrosine phosphatase -1B (PTP-1B) in resistance to diabetes. In their article, entitled "Increased Insulin Sensitivity and Obesity Resistance in Mice Lacking the Protein Tyrosine Phosphatase-1B Gene," the researchers show that PTP-1B plays a major role in the modulation of cell sensitivity to insulin. In simple terms, this means that we have managed to target a cellular mechanism that may eventually enable us to help in the treatment of type II diabetes and obesity in humans, says Tremblay of the 捆绑SM社区 Department of Biochemistry.
The work also suggests that PTP-1B may play a role in the gradual inability of insulin to regulate blood glucose levels. Up until now, this hypothesis had only been tested in vitro, explains Merck Frosst聮s research fellow, Dr Brian Kennedy. To check the viability of this hypothesis, Elchebly et al deleted the gene responsible for the production of this enzyme in mice. Mice whose cells lack PTP-1B do very well just the same, seeing that they maintain normal glucose levels after meals, and this using only one half of the amount of insulin required by their normal littermates.
Given that this research has been conducted in mice which lack the PTP-1B gene but which are in excellent health, the researchers at 捆绑SM社区 and Merck attempted to make them diabetic by placing both these mice and their normal littermates on a high-fat diet (50% of calories from fat).
"It was expected that they would all gain weight at the same rate," explains Kennedy. "However, it became obvious at the outset that the mutant mice would not attain the weight of the normal mice."
Furthermore, even the mice with only one of the two copies of the PTP-1B gene stayed thin. This means that it is not necessary to inhibit PTP-1B gene expression completely in order to regulate their weight, concludes Tremblay.
As stated by Dan Ferber in the March 5th issue of Science, "that means that a drug that blocks PTP-1B might safely treat both type 2 diabetes and obesity, which often go hand-in-hand."
"The work is very interesting and very important", says Phillip Gorden, director of the National Institute of Diabetes and Digestive and Kidney Diseases.
