Sequestration of centrally administered insulin by the brain: effects of starvation, aluminum, and TNF-alpha

Insulin found in the CNS may be a key regulator in the balance of energy in the body. Since the peripheral circulation is the principal source of insulin in the CNS, insulin must cross the blood-brain barrier. We examined the retention of radioactively labeled insulin in the brain and its transport from the brain after injection icv in mice. The results were compared with those found in mice after fasting, starvation, refeeding, and the addition of aluminum (previously shown to affect the transport of peptides from the CNS) as well as tumor necrosis factor-alpha (TNF-alpha) (known to interact with peripheral insulin). There was no obvious saturable transport system for insulin from the brain, but the retention of insulin was regulated by both aluminum and starvation. Although TNF-alpha was neither required nor involved chronically in the retention of insulin in the brain, acute ip administration of TNF-alpha produced an early increase in the retention of insulin similar to that found after starvation.