Intro to "Glucose-Stimulated-Insulin-Secretion" for blood sugar management.

The simplified Glucose-Stimulated-Insulin-Secretion (GSIS) process

1. When blood glucose increases, glucose is taken up into pancreatic beta cells through glucose transporters, there it is converted to ATP via aerobic oxidation.
2. As the ATP concentration increases, more ATP mediated Potassium channels will close, reducing the outflow of Potassium from the cells and therefore slowly depolarising the pancreatic islet beta cell membrane.
3. When membrane potential reaches the threshold voltage, voltage gated calcium channels open letting extracellular calcium ions into the cell.
4. As the calcium concentration increases, Insulin containing vesicles fuse with the membrane to release insulin into the extracellular space. This will then diffuse into the bloodstream to circulate throughout the body.
5. Calcium activated potassium channels then open, repolarising the membrane, hence closing the voltage gated calcium channels and halting the release of insulin.
6. More insulin is produced and stored, readying the system to repeat.

"explain GSIS to an inquisitive eight-year-old"

 When we eat foods known as "carbohydrates", these are broken down to smaller building blocks, including what we call "glucose". From our stomach and intestines this glucose goes into our circulating blood, from there it is taken all over our body. One organ the glucose goes into is the pancreas, which inside it contains cells known as "beta cells".

Like other cells in the body, these cells create energy carrying molecules known as "ATP" - think of these like batteries in our body. When more ATP is detected, the gates letting charged potassium out of the cells are closed, slowly increasing the difference in voltage across the cell wall.

From here we can think of the pancreas beta cells like little lakes with dams stopping water escaping. And the river below the lake is our blood travelling around our body. Like a lakes dam closing its gates, and stopping its water escaping, the water inside the walls will raise, making a bigger height difference on either side. This is the voltage across the walls of the cell. When the difference gets high enough, another gate will open, letting in more charged calcium particles into the dammed area. When enough of these are inside, this tells bubbles full of a chemical known as "insulin" to be released out of the dam and into the river (our blood).

We then also have other gates which open when they detect this calcium, which do so to let the potassium (ie. the water), then the voltage decreases (ie. the height of the water in the dam). This then signals for the gates letting the calcium into the dam to close as the voltage (water level) is too low. This then tells the insulin bubbles to stop being sent into the bloodstream (river). Now we are back to the start.

Discussion

I hope your eight year old self could keep up with that, but one key thing to learn from this is that the glucose controlled release of insulin is a circular and self resetting process which helps to moderate the release of insulin in pulses, to then give opportunity for a feedback loop to stop releasing insulin when blood glucose gets too low. 

Take heed that glucose is not the only molecule that controls the release of insulin, but also certain amino acids, fats and drugs can alter its release too. Many supplements and drugs (eg. metformin or berberine) work to release more insulin will work on the AMPK system which in turn amplifies the release of insulin in response to glucose by changing the sensitivity of the calcium activated potassium channels. More discussion on that will come in a future article.

If any one step in this chain is prevented from working due to damage to glucose transporters, mitochondrial (making the ATP), receptors, or a lack of insulin to release, then the system won't work or can operate poorly causing damage to other cells. These are some of the causes of chronically elevated blood glucose and insulin resistance, which are some causes of Type 2 Diabetes.

You may be wondering how Type 1 diabetes differs? This is when a person is unable to make insulin at all, or only very little, due to an autoimmune condition, where the immune system mistakes the beta cells in your pancreas as harmful and attacks them disrupting function. 

All up, thats GSIS in a summary. If you're interested in reading in more detail I suggest reading some of the articles linked in the references below. Next up will be discussion on ways in which we know we can the GSIS system can be up-regulated, or down-regulated, to change the amount of insulin released.

First to study, then to chat sh*t. -Thomas

Published: 23th November 2023

References

Regulation of Insulin Secretion in Human Pancreatic Islets (Oxford Centre for Diabetes, 2012)

Pathophysiology of Type 2 Diabetes Mellitus (Molecular Sciences, 2020)