The brain influences every tissue in the body, in many instances managing tissue processes to react to changing environmental or internal conditions. It is intimately involved in insulin signaling in various tissues, for example by:
- regulating insulin secretion by the pancreas (1)
- regulating glucose absorption by tissues in response to insulin (2)
- regulating the suppression of glucose production by the liver in response to insulin (3)
- regulating the trafficking of fatty acids in and out of fat cells in response to insulin (4, 5)
Insulin Resistance in the Brain
When a person eats carbohydrate or protein, the pancreas responds by increasing insulin secretion into the blood, and this provides nourishment to tissues and prevents the massive spike in blood glucose that would otherwise occur following carbohydrate consumption. It does this by two mechanisms, 1) by increasing the rate of glucose absorption by tissues, and 2) by suppressing the liver's secretion of glucose into the bloodstream. This year, Dr. Claudia P. Coomans and colleagues published a paper on the contribution of the brain to these processes (6).
By blocking insulin signaling in the brain specifically, they were able to reduce insulin-stimulated glucose uptake into muscle tissue by 59 percent in mice. The same procedure attenuated the ability of insulin to suppress glucose production by the liver by 20 percent. This implies that a significant part of insulin's ability to constrain blood glucose following a meal is mediated via the brain.
Then they performed the same experiment on mice that had been rendered obese by diet. Inhibiting insulin signaling in the brain had no effect in obese mice, indicating that the brain loses its ability to stimulate glucose uptake in obesity. If this finding can be generalized to humans, it suggests that one source of insulin resistance is the brain failing to stimulate other tissues to respond to it appropriately.
As it turns out, insulin resistance in the brain is a well described feature of diet-induced obesity in animal models (7, 8, 9). It occurs in parallel with leptin resistance, and is thought to also contribute to fat gain (10, 11). Obese humans appear to be leptin resistant in a manner that is very similar to obese animal models, and although it has not been demonstrated that brain insulin resistance occurs in parallel, it seems likely since this is consistently observed in animal models. Putting the pieces together, it is likely that insulin resistance in the brain occurs in humans and that it contributes to insulin resistance throughout the body.
How does insulin resistance develop in the brain? Probably in a manner that is fairly similar to how it develops in other tissues. Just as cellular energy excess and inflammation are implicated in insulin resistance in muscle tissue, the same mechanisms are implicated in leptin and insulin resistance in the brain, although there may well be other unidentified mechanisms that are unique to the brain (12, 13, 14). The treatment strategy, to the extent of my knowledge, should therefore be the same for both sources of insulin resistance.