Unlike muscle and fat tissue, the brain was long thought to be an insulin-independent organ. Since the discovery of insulin receptors, which are found in almost all brain cells, and the high density of insulin-dependent glucose transporters GLUT4 in the hippocampal region, it has become clear that insulin is a key component in the brain and especially for memory processes in the hippocampus (see info box). Since the brain depends on insulin to function, it is not surprising that it is also capable of producing its own insulin.
However, if insulin resistance is already present in the body, the blood-brain barrier provides only a reduced amount of insulin transporters for protection, which prevents the hormone insulin produced in the pancreas from passing into the brain tissue. Also, the brain’s own insulin synthesis may be decreased in response to insulin resistance in the body. In this way, insulin deficiency develops in the brain, a condition known as cerebral hypoinsulinemia, which has already been demonstrated in brains of people with Alzheimer’s disease. We now also speak of insulin resistance of the brain, which, however, is represented in the brain by an insulin deficiency, whereas in the insulin-resistant body there is rather an excess of insulin .
The resulting reduced insulin action is obviously amplified by impaired formation of important components of the insulin signaling cascade: thus, in addition to the insulin deficiency, a striking reduction of insulin receptors, of the insulin-like growth factor IGF and its receptors has been detected in the brains of Alzheimer’s patients. Even if sufficient insulin were present, it would not be able to exert its effect in this case because the signaling cascade is damaged. The AD brain thus becomes insulin resistant .