Your brain makes insulin - the same insulin produced by your pancreas. The same insulin that is not produced in people with type 1 diabetes and the same insulin that does not work properly in people with type 2 diabetes.
Author
- Craig Beall
Senior Lecturer in Experimental Diabetes, University of Exeter
Scientists have known for over 100 years about insulin producing cells in the pancreas. These spherical islands of cells, called islets, contain insulin producing beta cells.
But we've only just started to learn about brain insulin production. The fact that insulin is made there is still largely unknown, even among diabetes scientists, doctors and people with diabetes.
Yet, it was discovered there in the late 1970s - then promptly disregarded.
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A study published in 1978 showed the levels of insulin in the rat brain were "at least 10 times higher than that found in plasma … and in some regions … 100 times higher". If true, why isn't this more widely known.
Because soon after this discovery, clear evidence showed the transfer of insulin from blood to brain. One study in 1983 measuring insulin in rodent brain said that "insulin found in these extracts was ultimately derived from pancreatic insulin". They could not find the machinery to process insulin in the brain, at least with the tools available at the time.
This led to the assumption - for nearly the next 30 years - that all brain insulin came from the pancreas.
Insulin can and does move from the blood to the brain. But local sources of insulin are produced in specific places to do specific things.
The brain cells that make insulin
First, what is surprising about brain insulin production is that there is not one but at least six types of insulin-producing brain cell. Some have been confirmed in both rodent and human brain, others currently just in rodents.
One of the first brain cells shown to make insulin is the neurogliaform cell. These live in a brain area important for learning and memory. Most surprisingly, the production of insulin here depends on the amount of glucose present - a feature shared with pancreatic beta cells.
Its not clear what this insulin source does. Based on the location, it may contribute to cognitive function.
This area also has cells that create new neurons throughout life, called "neural progenitors". These cells also make insulin.
A similar cell from the olfactory bulb, the processing centre for smell, also has insulin-producing progenitors. What insulin does here is still unknown.
But one insulin producing brain cell might regulate growth. A 2020 study showed that insulin is made and released from stress-sensing neurons in the mouse hypothalamus. This is a brain area that controls growth and metabolism. It also has the highest insulin levels in the human brain .
The researchers showed that stressing mice caused hypothalamic insulin production to decrease. This led to poorer growth in the animals. In the case of mice, their bodies were shorter.
Hypothalamic insulin maintained growth hormone levels in the pituitary gland. This is sometimes called the master gland as its involved in making or controlling production of other hormones. Having less local insulin meant less growth hormone production.
Then there is the choroid plexus. This is the brain region that makes cerebrospinal fluid. In humans, that is about half a litre of this clear colourless liquid every day.
Cells lining the choroid plexus - the epithelial cells - make a nourishing broth of growth factors and nutrients to keep the brain healthy. Only recently was insulin production found here in mice.
The choroid plexus secretes fluid directly into brain ventricles, the spaces deep inside the brain. This fluid flows around the whole brain, perhaps delivering insulin more widely.
One place it does travel to is the appetite control centre in the hypothalamus.
A 2023 study in mice showed that genetic control of insulin production by the choroid plexus could change food intake. The hypothalamus was rewired by changing choroid plexus insulin levels. Insulin released from here suppressed appetite.
Another source of insulin in the brain also reduces food intake. A 2022 found that insulin producing neurons at the back of the brain, called the hindbrain, reduced food intake in mice.
Might help the brain stay healthy as we age
So if brain insulin can change appetite, does it control blood sugar?
No. At least there is no evidence for this currently. It is unlikely this insulin leaves the brain. Therefore, its unlikely to control glucose levels in the same way.
Instead, insulin in the brain might help the brain stay healthy as we age. For example, Alzheimer's disease is often, unofficially, termed type 3 diabetes. This is because the brain is insulin resistant in Alzheimer's. It cannot properly use glucose either.
This is a big problem. Glucose is the main fuel for the brain. In fact, estimates suggest there is a 20% energy gap in Alzheimer's. Even without brain cell loss, this alone will impair cognitive performance.
This has led to attempts to boost brain insulin. Spraying insulin into the nose can improve cognitive performance in Alzheimer's, in some, but not all studies.
Brain glucose use also decreases over time and intranasal insulin also seems to limit this decrease.
Therefore, is more brain insulin always a good thing?
Not necessarily. In women specifically , higher levels of insulin in cerebrospinal fluid is associated with poorer cognitive performance.
There is still much to learn about brain insulin production. For example, which insulin source came first? The brain or the beta cell? Hopefully it doesn't take another 30 years to find out.
But given the strength of evidence of brain insulin production, it won't be long until our school textbooks are updated.
Craig Beall currently receives funding from Diabetes UK, Breakthrough T1D, Steve Morgan Foundation Type 1 Diabetes Grand Challenge, Medical Research Council, NC3Rs, Society for Endocrinology and British Society for Neuroendocrinology.
