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The story of insulin resistance and the floating doors

Posted by Dr Sandy on in Diabetes | 585 Views | Leave a response

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Click to listen to the audio…

The cause of insulin resistance is………………insulin

soluble insulin receptor floating about

Insulin is LOOKING for insulin receptors, NOT CELLS. It turns out, in people with insulin resistance, insulin receptors can be circulating WITHOUT CELLS. Oh dear !

It all begins with a visit from insulin…….

He climbs the stairs, knocks on the door and EXPECTS magic to happen i.e.

the cell should lay out a red carpet and let insulin inside.

From the inside, he can do his job.

Insulin doing his job

When insulin resistance occurs, this DOES NOT HAPPEN.

Actually………….. NOTHING happens.

This causes trouble on the inside, impacting fuel supplies and trouble on the outside, the nutrients have nowhere to go.

And start accumulating…… sugars “gum” up the works.

So let’s review what is supposed to happen…..

Insulin 101

The pancreas distributes insulin parcels in response to glucose.

Now the parcels don’t go directly from the pancreas to muscle and fat tissues, they have to pass through the liver. Approx. half of the insulin secreted by the pancreas makes it out of the liver.

From here, insulin goes about hist business, which is to put the groceries away, after dinner, specifically in muscle and fat tissue.

Binding to the insulin receptor

Now most cells have an insulin receptor or two.  So there are lots of places insulin can visit.  As far as insulin is concerned, if “he” sees an insulin receptor, it’s a welcome mat.

He knocks on the door – expecting some kind of response.

What he gets up to,  once he makes it inside, depends on the cell he is visiting.

Looking for the welcome mat

The point……………. insulin is LOOKING for insulin receptors.

NOT CELLS.

And…. it turns out, that it is possible for insulin receptors to circulating WITHOUT CELLS.

This  is what a group of Mexican researchers recently discovered…..

Soluble insulin receptors

They started by looking for “unattached” insulin receptors in rats.   Now they needed rats, with metabolic problems, so they took ordinary Wistar rats and fed them, TOO MUCH SUGAR.   It took about 8 weeks to create animals with metabolic problems.

Which showed up as high fasting insulin and sugar levels.

Nothing new here.

A closer look at that high insulin

The team looked  at the “size” of the insulin molecules floating in the serum (blood).

Approx 40 % of the insulin was BIGGER than predicted.

Suggesting the insulin was attached to something. Using antibodies that can pick up the insulin receptor, the team confirmed the something the insulin was attached to was an insulin receptor.

It happens in humans too

They did the same investigation in humans.

Just as in the case of the rats,  the insulin that is circulating is not always free, it is attached to “floating” insulin receptors.

Now this happens in both healthy and diabetic folks.

But, it’s a bigger issue in the metabolically “broken” – these people have a lot more insulin floating in the blood (hyperinsulinemia) and a higher percentage of what is “floating”, is bound to soluble insulin receptors.

Here is the data.

graph showing soluble insulin receptor levels

Comparison of soluble insulin receptor levels in healthy people and diabetic patients. © 2014 Hiriart et al.

Does it matter ?

Probably.  If insulin is knocking on “floating” doors, instead of “real” doors, the response to insulin is going to be impeded.

Insulin resistance anyone ?

So why  are the insulin receptors being jettisoned ?

Insulin sparks the receptor dump

Curious, the team exposed liver cells, to different concentrations of insulin in a petri dish and watched what happened.

Prolonged exposure (100 hours) to continuously high levels of insulin, prompted the liver cells to jettison their insulin receptors.

insulin causing insulin receptor shedding

Effect of insulin on level of soluble insulin receptor shedding. Copyright 2014 Hiriart et al

The amount of shedding was proportional to the amount of insulin i.e. more insulin, caused more shedding.

It’s a matter of survival

Putting two and two together…………..

Insulin causes both blood pressure and sugar levels to drop precipitously.

The liver cells are thus the first cells to encounter insulin, being mindful of the potential danger, the elevated insulin levels pose, sparks a “defensive” process, that causes the insulin receptors, to be jettisoned off.

When insulin binds to these “floating” insulin receptors, the effective concentration of insulin,  is instantly lowered …..

To “safe” levels.

Too safe ?

With a high percentage of insulin, TIED UP, literally, the actual amount of insulin being delivered to muscle cells and fat cells is significantly diminished.

They’re NOT deliberating ignoring insulin’s cries.

Insulin is NOT there.

So…………… the glucose gates are not translocated.  Insulin is not able to put the glucose away timeously.  This results in high sugar levels, which creates a bit of a panic.  More insulin is dispatched……………

Once more there is a problem with DELIVERY.

Eish !

Rein in insulin

This research suggests, the drama begins with TOO MUCH INSULIN, not insulin resistance.

So…………… to improve your levels of “insulin resistance”, you need to work at bringing down your insulin levels, through diet and lifestyle.   Click here for some suggestions.

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Hyperinsulinemia is associated with increased soluble insulin receptors release from hepatocytes. Frontiers in Endocrinology (2014) Vol 5: article 95.  Marcia Hiriart, Carmen Sanchez-Soto, Carlos Manlio Diaz-Garcia, DianaT. Castanares, Morena Avitia, MyrianVelasco, Jaime Mas-Oliva, Marina Macias-Silva, Clicerio González-Villalpando, Blanca Delgado-Coello, Marcela Sosa-Garrocho, RománVidaltamayo and Deyanira Fuentes-Silva.

Further reading

insulin struggling to open blood vessel

Could a little bump on a blood vessel be the reason you’re insulin resistant ?

Insulin needs wide blood vessels to work, but widening blood vessels causes blood pressure to drop – the carotid body, keeps things in balance. Hopefully.

insulin as a knight

It’s time diabetics stop seeing insulin as a knight in shining armour

SUGAR is the enemy and INSULIN is the saviour. The “success” of bariatric surgery, as a treatment for type 2 diabetes, is forcing a re-think of the story.

too much insulin not too little

You want LESS insulin, NOT MORE, if you have type 2 diabetes

Normal mice, fed a normal diet but given, EXCESS insulin, develop type 2 diabetes. More insulin is NOT the cure for type 2 diabetes.

 

Looking for tips & strategies to improve  your insulin sensitivity ?

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Posted in Diabetes | Tagged hyperinsulinemia, insulin, insulin receptors, insulin resistance, liver, pancreas

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Located in Johannesburg, South Africa

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