Sunday, November 22, 2009

Serotonin and Insulin Secretion

Most of us have heard of serotonin (5-hydroxytryptamine, or 5-HT) as a neurotransmitter. It's the compound that is affected by the SSRI antidepressants.

Nerves use neurotransmitters to transmit messages from one nerve cell to the next. The nerve's signal arrives at the end of one nerve, which then secretes a neurotransmitter. This diffuses across the tiny space between the nerves and is taken up by the next nerve. The neurotransmitter is then reabsorbed by the first nerve and can be used again. The reabsorption also prevents the signal from becoming permanent.

The SSRIs slow down the reuptake of the neurotransmitter so its effects last longer. Serotonin can affect mood, and low levels can cause depression. Hence keeping it around longer by means of the SSRI drugs can reduce depression.

So what does all this have to do with diabetes?

A fascinating new article that appeared in the open-access journal
PLOS recently shows that serotonin in beta cells is required for insulin secretion. A summary of the article appears here.

Apparently it's been known for 30 years that serotonin is synthesized in beta cells and cosecreted from the beta cells along with insulin, but no one knew why, and most textbooks -- even comprehensive ones -- didn't even mention this fact.

But this German research group showed that mice unable to produce serotonin outside the nervous system became diabetic. Infusing them with serotonin corrected the problem.

So all we have to do is take serotonin tabs and all our problems will disappear? Unfortunately, no.

The crucial factor here is whether the serotonin is inside the cell or outside the cell. High serotonin inside the cell stimulates insulin release. High serotonin outside the cell inhibits insulin release. It's the ratio that is important.

So when internal serotonin levels are high, insulin and serotonin are cosecreted. The secreted serotonin then inhibits further insulin release. Gradually the secreted serotonin is taken up again by the beta cells, until there's more inside the cell than outside the cell. Then the cell can secrete more insulin.

The authors postulate that this system is responsible for the well-known insulin pulses that occur in nondiabetic people between meals. This pulsating pattern is lost in people with type 2 diabetes.

This research is also fascinating for a more general reason. Most water-soluble hormones like serotonin, histamine, and the catecholamines were thought to work at the surface of the cell. They bind to a surface receptor in the membrane, causing conformational changes that affect the metabolism inside the cell. This is true of insulin, for example.

Other hormones, the lipid-soluble ones like thyroid hormone and the steroid hormones, get inside the cell and bind receptors in the nucleus, changing the expression of genes.

But this study showed that serotonin works inside the beta cell in a very different way. It doesn't just bind to a receptor. Instead it works by actually forming bonds with other compounds in the cell, called
serotonylation. This action is very different from the way serotonin works as a neurotransmitter.

Serotonylation had previously been found in platelet-forming cells and in smooth muscle cells. Finding it in beta cells suggests that it may turn out to be a general property in many kinds of cells.

This will open the door to a lot more research on how hormones work as well as research to find new drugs that work to control hormone action.

And I hope it results in new treatments for diabetes of all kinds.


  1. Thank you so much for the clear explanation.

  2. So, might it help to take 5HTP capsules?

  3. See above: "So all we have to do is take serotonin tabs and all our problems will disappear? Unfortunately, no" and the copy that follows.

    I wish it were so simple.

    But who knows. Maybe it would help. Serotonin and 5-HTP (the precursor of 5-HT) are sold as supplements and a lot of people are probably taking them, they're probably reasonably safe.

    But here's what Wickipedia says: "Due to the conversion of 5-HTP into serotonin by the liver, there is a significant risk of heart valve disease from serotonin's effect on the heart.[34][35] In Europe, 5-HTP is prescribed with carbidopa to prevent the conversion of 5-HTP into serotonin until it reaches the brain [36]. . . . 5-HTP is usually converted to serotonin before it can reach the brain, elevating blood serotonin levels greatly, which may cause diarrhea and heart problems, while only slightly increasing brain serotonin."

    You might talk to a pharmacist before taking a lot of this.

    Be careful.

  4. I was diagnosed with type 2 diabetes about 18 months ago. Found it by accident. Was having panic attacks, in emergency room three times with them. Doctor decided to do blood workup. Found diabetes, now where did that come from? Have been on Paxil for 18 months, have gained weight, also taking Metformin. I have weaned myself off of the Paxil. Now wondering is diabetes developed because of panic disorder, which happened out the blue about 4 years. I am going to research this 5HTP supplement and see if I can get a handle on this.

  5. Anonymous, Some people think stress can trigger type 2 in a person who already has a predisposition.

  6. What about the inverse? If you have too much extra insulin, does it effect the production of serotonin or other hormones?

  7. Alpha blockers (especially alpha2) blockers increase insulin => insulin resistance. When you withdraw you have less insulin and its recipe for diabetes.

    Muscarinic m3 bockers does this too.

    Seroquel + mirtazapine are alpha2 blockers. So they cause diabetes easily (if dose is reduced).

  8. The symptoms you speak of regarding heart problems are probably associated with Serotonin excess known as Serotonin Syndrome which can come about by taking something like an SSRI (prevents quick metabolism of serotonin locking it into receptor sites) and taking serotonin itself (or any metabolite that can increase serotonin production).

    For what it's worth, taking either serotonin or melatonin can lead to overdose, but taking the metabolite 5HTP is less likely to result in such as your own body will use as much as it needs to convert.

    Most people these days who burn the candle at both ends, do not get enough sleep, and who eat too many processed foods and sugars, high carb foods or take too much caffeine are deficient in serotonin and possibly many other brain chemicals toboot.

    5HTP has been proven in studies as early as 1972 to assist people with obesity by correcting the above problem and getting rid of cravings for sweet foods or carbs. Something the average person with insulin resistance, type 2 etc needs if anything.

    There are NO reports of 5HTP causing heart problems that I can see anywhere. Those types of side effects are more common in people actually taking serotonin itself in high doses or as I said earlier, mixing with SSRI's which in some cases cause high levels to build up.

  9. Too little serotonin prevents insulin from metabolism glucose etc correctly. And no... you can still produce serotonin with high levels of insulin as long as you are getting good foods containing L Tryptophan as well as B6, magnesium which are required to convert L Tryptophan into serotonin. A lot of people arn't actively doing that though, and are often not getting enough sleep, are stressed, drinking too much caffeine, and stress (high cortisol) combined with low serotonin will cause a lot of problems there with carb cravings.

  10. I love it Gretchen. Very powerful information! wonder if serotonin deficit has anything to do with diabetic gastroparesis too. SIBO could be the enemy, or lack of neutral amino acid carrier(Hartnup's Syndrome) or even achlorhydria. following all your investigative work from now on.

  11. I have been type 1duabetic for 50 years. On my early twenties developed mood swings with aggression Was put on SSRIs Have been on them for 30 years. I recently took 3 months to get off them. Had horrible aggressive behavior. Trying to decide if I want to get back on them. I read that type 1 can deplete serotonin levels. Is this true. If true I think I'd better get back on it. This anger is hard to control. Help wanted on this matter.

  12. Does type1 diabetes deplete Seratonin levels? I read this years ago. Been type1 50 years. Want to get off Celexa but am afraid mood swings will return.

  13. Cindy, I'm hardly an expert on type 1. If SSRIs are helping you, why do you want to get off them? I agree that all meds do have side effects, and it's often a difficult choice to decide which is best approach.

    These articles might be relevant.