Insulin-like growth factor 1 regulates developing brain glucose metabolism

The brain has enormous anabolic needs during early postnatal development, T his study presents multiple lines of evidence showing that endogenous brain insulin-like growth factor 1 (Igf1) serves an essential, insulin-like role in promoting neuronal glucose utilization and growth during this period. B rain 2-deoxy-D-[1-C-14]glucose uptake parallels Igf1 expression in wild-typ e mice and is profoundly reduced in Igf1-/- mice, particularly in those str uctures where Igf1 is normally most highly expressed. 2-Deoxy-D-[1-C-14]glu cose is significantly reduced in synaptosomes prepared from Igf1-/- brains, and the deficit is corrected by inclusion of Igf1 in the incubation medium . The serine/threonine kinase Akt/PKB is a major target of insulin-signalin g in the regulation of glucose transport via the facilitative glucose trans porter (GLUT4) and glycogen synthesis in peripheral tissues. Phosphorylatio n of Akt and GLUT4 expression are reduced in Igf1-/- neurons. Phosphorylati on of glycogen synthase kinase 3 beta and glycogen accumulation also are re duced in Igf1-/- neurons. These data support the hypothesis that endogenous brain Igf1 serves an anabolic, insulin-like role in developing brain metab olism.