Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting onto astrocytes in concert with insulin-like growth factor I (IGF-I). Cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a MAPK/PKD pathway resulting in translocation of glucose transporter 1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein, C terminus (GPIC) and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes.
- Received July 19, 2016.
- Accepted September 27, 2016.
- © 2016 by the American Diabetes Association.