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.