Insulin in the brain affects cognition, appetite and weight

Insulin has long been known as crucial for muscle, liver and adipose tissue metabolism. It's effect in the brain on cognition, behavior and physiology is a more recent focus described in an excellent paper published recently in Nature Reviews Endocrinology.

The brain is sensitive to insulin

Since glucose uptake into the brain occurs independently it took a while to recognize the function of the receptors that are found there. The first clue came with the brain-specific knockout mouse model of the insulin receptor.

"Such knockout mice became obese due to increased food intake and developed whole-body insulin resistance with increased plasma levels of insulin and dyslipidaemia."

Then investigations comparing infusion of insulin versus saline on human brain activity has widespread effects.

"...these studies provided strong evidence that systemic insulin administration modulates cortical brain activity in humans...not only homeostatic areas (as shown in animal studies) but also higher functional areas involved in sensory and cognitive processes."

And intranasal administration was shown to affect basal and evoked brain activity. How does it naturally get there?

Whole body insulin resistance affects the brain

"...various studies in animals clearly demonstrated that insulin was transported across the blood–brain barrier by a saturable transport system..."

And it humans it gets from the CSF (cerebrospinal fluid) through the BBB (blood brain barrier).

"Concentrations of insulin in the CSF increase when the hormone is administered into the bloodstream, again indicating transport across the blood–CSF barrier."

Importantly, insulin resistance in the rest of the body affects the brain, and this has been associated with Alzheimer's disease.

"Insulin transport into CSF is attenuated in individuals with reduced whole-body insulin sensitivity, which suggests that insulin resistance at the blood–CSF barrier could impair transport of the hormone into the brain. Accordingly, insulin concentrations in CSF are lower in individuals with obesity, who are generally more insulin resistant, than in people without obesity. Furthermore, insulin concentrations within brain tissue and CSF are reduced in older individuals...In Alzheimer disease, a condition often associated with insulin resistance, insulin levels in the CSF have been reported to be reduced."