Too much zinc deep inside the insulin secretory granules of  beta cells, generates additional stress, especially if you’re insulin resistant.  Use zinc supplements wisely !

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The sting in the tail of zinc supplements

Too much zinc deep inside the insulin secretory granules of beta cells, generates additional stress, especially if you’re insulin resistant. Supplement wisely !

There are quite a few genes linked to type 2 diabetes.  Now to be clear, none of them actually cause type 2 diabetes, per se.

It’s a summative process.

If you happened to have inherited a so called bad version of a gene, usually everything still works, but  your biology is marginally different.  The more dicey versions you have, the less wiggle room you have and the higher the odds, your biology FAILS.

In the case of type 2 diabetes, the fail is usually attributed to  beta cells.

A risky gene

One of the genes, that makes beta cells vulnerable, is the gene which codes for the zinc transporter, which helps to package and release insulin into the beta cell secretory granule.

The gene  is the SLC30A8 gene – it codes for the ZnT8 transporter.

You see, zinc and insulin’s biology are interconnected…….

Bring on the zinc

When insulin makes the big leap, into the portal circulation, zinc is right there by his side.

Manufactures of exogenous insulin, have known this for years…. so if you read the label, you’ll see, zinc is a key ingredient in insulin therapies.  And, multiple studies have shown, zinc supplementation is able to improve glycemic control.

In fact, zinc has been categorized as an insulin mimetic.

Zinc a helper and a hindrance

At the level of the insulin receptor, zinc helps to supercharge responses………..so it keeps things humming along nicely.

But at the level of the beta cell, zinc actually inhibits insulin secretion.

Eish !  Confused……..

Think location, location, location !

Insulin kinetics

What’s not always appreciated, is the amount of insulin circulating depends on how much the pancreas produces and how much the liver “extracts”.  Under normal circumstances, the liver clears around 50 % of the insulin which arrives from the pancreas, this means if ten insulin molecules  produced, only five will leave the  liver and  actually circulate in the body.

When there is lots of zinc around, a much higher proportion, makes it through.

Which is most helpful.

It means that there is more than enough insulin arrives at muscle and fat cells,  to get the job done.  Sugar is quickly put away and a sugar spike is avoided.

But it is a totally different story…………

In the islets

Within the Islet of Langerhans, the presence of zinc, is a signal that a squirt of insulin has gone out, so “everyone” should “stand down” and wait to see what happens.

Overshooting the insulin response can be life threatening.

The everyone particularly applies to beta cells,  but it also applies to alpha cells.  In the case of the alpha cells, they’re producing glucagon and ….

Glucagon keeps sugar flowing.

Something the brain appreciates, but from the beta cell’s perspective this is counter productive. More sugar,  requires more insulin, so shutting glucagon secretion down, is very helpful.

So at the end of the day, zinc is most helpful………..especially dietary zinc.

Dietary zinc faces travel restrictions

Now the absorption of zinc is a tightly regulated process, with lots of checks and balances in place, to keep the body’s zinc levels, just right.

Not too much.  Not too little.

The tiny amount of  zinc coming in with dinner,  will pass through the liver and could potentially give insulin a helping hand.

Maybe, maybe not………… the amount is tiny.

Dietary zinc will not travel to “the islands”, so there is no possibility of causing trouble inside the pancreas itself.

What about zinc supplements

Well, if they’re taken WITH DINNER, they too can lend a helping hand, in the liver.  And since the level of zinc in a zinc supplements, is significantly higher than your average dinner.

The impact is more likely to be clinically significant.

So bring on the zinc supplements – there is plenty of science to suggest, they make a difference.

IN THE SHORT TERM at least.

But what about that zinc transporter gene ?  What’s the story here ?  And could there be downside to blocking insulin clearance ?

ZnT8 options

Well  quite a few variations of the ZnT8 transporter gene have been described, some are exceedingly rare and two are pretty common. The notable one,  designated  rs13266634 version, is the most common version of the gene, with a prevalence in the order of 70 %.

The transporter that it makes, has replaced the  tryptophan amino acid, at the 325 position, with an arginine.

It’s one tiny difference.

But it programmes the production of a HIGHLY efficient zinc transporter.

More zinc………… should be a good thing.

Actually, it’s  the risk variant…….

Eish !  Biology is complicated at this stage no one knows for sure, what the problem is…

Blame amylin ?

When researchers create ZnT8 mutants in mice – the results are not very predictable. Hinting that this might be one place, where human biology and mouse biology, part ways.  Now one of the known differences between mice and men is the nature of a protein called amylin (also known as islet amyloid polypeptide).

Amylin is also produced by beta cells and is  inside those insulin secretory granules.

Just like zinc, it is secreted alongside insulin and helps insulin to do his job i.e. to put away the groceries.

Now the way amylin helps, is  it regulates your appetite.

The squirt of amylin, prompts you to feel more satisfied i.e. less hungry, so you stop eating.  Hopefully !  With less food  coming in, insulin can get down to business and   put away the current batch of groceries.

Humans are odd balls

Mice and rats have amylin.

But, their version doesn’t have a tendency to clump.

The human amylin peptide, has a little tweak in the amino acid sequence, so it  can  form aggregates and these aggregates have been shown to be toxic to beta cells.

In fact, amylin aggregates are often seen in the pancreas of people who have died with type 2 diabetes, but they are not seen in non-diabetics.

So amylin CAN aggregate, but under normal circumstances, it isn’t a problem.

The sticky side of amylin

Instead of sticking to itself, amylin likes to stick to insulin.

But so does zinc.

Since zinc offers insulin a lot more benefits, given a choice, insulin picks zinc.  And this makes……..

Zinc the swing factor

More zinc leads to MORE aggregating.

Because less free insulin is available to bind to amylin.

Researchers believe this might be why people who inherit  a less efficient or dysfunctional ZnT8, are less likely to develop type 2 diabetes.

It’s NOT the cause…..

Aggregation happens

But, when insulin production shuts down for the night, the clean up crew takes care of the aggregates that have formed.

More or less aggregates – it’s NOT an issue.

Until…..

There is no downtime

The continuously high demand for insulin : morning, noon and night, which characterizes someone who is insulin resistant……….. puts the beta cells under stress.

Leaving less time for clean ups.

And in these circumstances, more aggregates become more of a problem.  The longer it goes on for, the bigger the fall out.

Culminating in a diagnosis of type 2 diabetes.

So where does this leave zinc supplements ?

At this stage, there is NO EVIDENCE that zinc supplements cause trouble.  Not yet !  But realize, it’s  expensive to study people for years and years, so zinc supplement studies are SHORT TERM studies.

Table summarizing the meta analysis of zinc supplementation trails taken from Am J Clin Nutr (2019) 110:76–90.

1 month.  3 months.  A year at a push.

The doses are typically a lot lower than the doses that are currently being punted to boost immunity and fight off infections.

You need around 3 mg a day.

If your diet is poor and you have other issues, maybe a little more.

Use zinc supplements wisely

Based on the biology….

50 mg/day, day in and day out for months/years is likely to have unintended consequences.

If your diet is low zinc or your sugar levels are “out of control”, only take a low dose zinc supplement and make sure you take it with food !

Further reading

 
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