This limb which includes a gland of yours was cultivated from your own cells in vitro.

The extracted hormone is stored and refrigerated.

The glass casing is appropriate for the living room and a microphone can record and enhance the sound of dripping.
-- pashute, Jul 26 2022

I think that this
-- pocmloc, Jul 26 2022


//I think that this//

I think so too. [+]
-- pertinax, Jul 26 2022


Sounds good but... don't our existing external glands already get us in enough trouble?
-- 2 fries shy of a happy meal, Jul 27 2022


I'm wearing one right now. But i have to fill it with insulin which I must buy every month at the pharmacy. And it is not immediately reactive, it is slowly released in the body with a 20 minute delayed action.

I wonder if the mechanism of determining the sugar level that signals the pancreas to create and release insulin is fully understood. Ill ask on the WP pancreas talk page.
-- pashute, Jul 28 2022


//I think so too//

what [pertinax] said
-- pashute, Jul 28 2022


//I wonder if the mechanism of determining the sugar level that signals the pancreas to create and release insulin is fully understood.//

I wouldn't go with "fully" understood, but we're most of the way there. It's a pretty janky cobbled-together system by the standards of biology. Working backwards somewhat, it goes like this:

To get secretion of insulin, you have to depolarize the plasma membrane. This is a common feature in all things secretory, neurons "firing" is them depolarizing their membrane, muscles of all types etc. all pull the same trick.

The next step is calcium, more specifically, soluble ionized Ca2+. At rest, there is a VERY small amount of this inside cells and a very large concentration outside. There are channels that specifically let Ca2+ into the cell when the membrane is depolarized. Increased Ca2+ inside the cell is the "Go" signal. Same in all cells, same trick repeated and adapted, just the outputs vary.

The weird part is how the membrane potential depolarization is triggered. The main mechanism used in almost everything is a signal molecule (hormone, neurotransmitter etc.) binds to a specific receptor. These are very tightly controlled, and specific and work very well at TINY concentrations. In the pancreatic beta cells, we need to use glucose. This is always around at fairly high concentrations: 0.5-20mM,vs 0.1-10pM of something like the hormone CCK that triggers digestive enzyme secretion. Somewhere in the billion to trillion fold less.

So the glucose enters the cell, and is metabolized in the normal aerobic glycolysis and mitochondrial pathways. There are some tweaks to make it concentration specific. This increases ATP levels and THAT is the signal to depolarize the membrane>increase Ca2+>cause secretion.

This is deeply weird, since all cells normally rest in the highest energy state. Their ATP levels are maintained at the highest levels, as a reserve for when workload comes along. Beta cells rest with low ATP, this is a bit like controlling a car's speed by filling the gas tank. It's this deep metabolic weirdness that probably makes them vulnerable. They can't proliferate, unlike the rest of the pancreas. Chronic damage to many tissues can be tolerated, at least for a while, by killing off damaged cells and making new ones. The same paradigm in beta cells just ends up with fewer and fewer cells.

There have been a few discoveries over recent years, but ultimately they're all amplifiers/suppressors of the same cascade.
-- bs0u0155, Jul 28 2022


//gland of yours was cultivated from your own cells in vitro.//

You're really not going to like the maintenance required. As a start, you need a carefully controlled atmospheric gas mix, usually set at 5% CO2 to enable the bicarbonate pH buffering to work. Your temperature can't vary by more than ~0.2C, that's normally done by having a big mass of water in the heating system. Then you need the extracellular fluid mimetic that the cells live in, all the salts etc. are all understood, and sterile solutions come in at ~$100/litre. You'll need to supplement that however, since the complex mix of fatty acids, serum proteins, hormones etc. isn't fully understood or artificially replicable. So we usually go with about 10% fetal bovine serum to keep the cells happy. That's more pricey ~$1000/litre. Then because you have no immune system, you'll need constant antibiotics.

You'll need some kind of aeration to replace circulation or the organ-scale cell clusters become necrotic. Then you need a mechanism of stimulating the hormone release, that's almost always another hormone, from...?

It's easier to make up a plasmid for your hormone of choice, make a stable expression cell line in something like HEK293 and harvest the media. You'll likely need an affinity purification system, and all this has to be done sterile.

Some cell lines just secrete hormones, HepG2 for example secretes human EPO, even more so if you dial down the oxygen somewhat. The problem there is that HepG2 cells live in media with the aforementioned FBS, so you have to work out how to isolate your EPO from all the other cow proteins.
-- bs0u0155, Jul 28 2022



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