Discovery of How Insulin Allows Entry of Glucose Into 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 study’s corresponding author, Joshua Zimmerberg, M.D., Ph.D., chief of NICHD’s Laboratory of Cellular and Molecular Biophysics. Glucose is ferried through the cell’s 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 NIDDK’s 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 cell’s surface. The vesicles travel along a railroad track-like network of molecules known as microtubules. When insulin binds to the cell’s outer surface, those vesicles immediately stop moving, tether to the cell’s 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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