Researchers from the National Institutes of Health have discovered the critical sequence of events by which insulin stimulates the entry of glucose into fat cells.
The study, appearing in the May 9 issue of Journal of Cell Biology, was conducted by researchers from the National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive and Kidney Diseases.
This finding provides useful information for understanding disorders in which cells have difficulty using insulin, such as insulin resistance and type 2 diabetes, said NICHD Director Duane Alexander, M.D.
Glucose, a simple sugar, is a nutrient that cells need to survive, explained the studys corresponding author, Joshua Zimmerberg, M.D., Ph.D., chief of NICHDs Laboratory of Cellular and Molecular Biophysics. Glucose is ferried through the cells outer covering, or membrane, by a family of molecules known as glucose transporters. In the study, the researchers discovered how glucose transporter 4 (GLUT 4) carried insulin into fat cells.
Previously, scientists had learned that, within the cell, GLUT 4 is contained in the membrane of tiny sacs known as vesicles. Another author of the current study, Samuel Cushman, Ph.D., of NIDDKs Diabetes Branch, had found in earlier studies that GLUT 4 was transferred from the vesicles within the cell to the cell membrane, when the vesicles combined, or fused with, the membrane. Researchers had been unable to determine, however, where in the cell the vesicles were stored and how insulin stimulated them to fuse with the cell membrane.
In the current study, the NIH researchers observed fat cells taken from mice and learned that the GLUT 4 vesicles are highly active. They discovered that, although a few vesicles are scattered throughout the cell, the majority circulate just under the cells surface. The vesicles travel along a railroad track-like network of molecules known as microtubules. When insulin binds to the cells outer surface, those vesicles immediately stop moving, tether to the cells inner surface, then fuse with the cell membrane. GLUT 4, contained in the vesicles membrane, then enters the cell membrane, where it ferries glucose into the cell.
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