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Hepcidin in insulin resistance

Posted by Dr Sandy on in IR | 666 Views | Leave a response

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When you’re insulin resistant, that is, you’ve got  metabolic syndrome, pretty much every chemical in the body is NOT QUITE RIGHT.  Some are up.  Some are down.  Few are actually at physiologically NORMAL levels.

Traditionally the focus is on the big guns.

  • Sugar
  • Insulin
  • And cholesterol

In this series, we  take a look at some of the other players.

Who they are, what they’re up to and how they’re part of the state of insulin resistance.

This week, we’re not actually looking at a chemical per se, instead we take a look at the behaviour of tiny little pressure receptors, called baroreceptors, which are embedded in the blood vessels, that leave the heart.

Hepcidin in the insulin resistant

Now, hepcidin is UP  and this impacts iron metabolism –  typically manifesting an “apparent” iron deficiency.

So who is hepcidin ?

The mining magnet

Well is a mining magnet, controlling the acquisition, storage and utilization of iron in the body.

He controls EVERY cell’s access to IRON, either directly or indirectly.

And EVERY CELL,   includes all  the cells that make up the human body, from your brain to your big toe, as well as any microbial cells, keen to take up residence.

In the body, iron is a precious commodity,  it runs a lot of chemistry……..

The chemistry of iron

The chemistry that springs to mind, for most people is oxygen delivery.  Iron is the molecule at the centre of haemoglobin, which is the protein responsible for carrying and delivering oxygen.

And oxygen is a REQUIREMENT for life.

oxygen delivery

But, iron is involved in respiration, DNA synthesis, detoxification, regulation of gene expression, as well as growth and development. Overt shortages of iron, typically show up, as anaemia.

Anaemia is not ALWAYS about iron……………but 9 times out of 10, it is.

Hepcidin is a shrewd business man

When you run a mining operation, is not the same, as running a bank, you’ve got to be tough and hands on.  Hepcidin, uses brute force, to run the mining operation.   His modus operandi, is to control the one and only, iron exporter pump.

Hepcidin, renders this pump, inoperable.

In one foul swoop, hepcidin controls the  entire iron supply chain…..

Ferroportin pumps

Are located  in several types of cells, notably

  • Enterocytes, which are the cells that line the gut and
  • Marcophages, the workhorses of the immune system

The enterocytes are responsible for iron uptake, while  the macrophages control iron distrubtion.

Iron uptake takes a knock

Disabling ferriportin in the enterocytes, stops mining operations.

It all starts with dietary iron, which maybe bountiful or rather iron deficient.    Either way,  the enterocytes grab as many iron molecules, as  they can, when they pass their way.    The iron that is gathered is then moved inside for storage.  From here it is moved into the body, by the ferriportin pump.

ferriportin on enterocytes

Assuming the pump is operational.

no iron entering circulation

If not, well the iron is stored, until it can be moved out or the enterocyte falls into the abyss –  which ever comes first.

NOTE :  Enterocytes days are numbered, they live for 3 – 5 days.  They’re born in the villi crypts and then move up, to the top of the villi, where they get sloughed off.  When this happens, they take their iron supply with them.  

So iron uptake takes a knock……

Iron distribution is ALSO curtailed

Macrophages come in different shapes, the one’s stationed in the spleen are professional,  iron guzzlers.

Old, damaged red blood cells, are euthanized in the spleen. It’s a controlled process, very civilized, the macrophages in the red pulp, gather all the iron, the red blood cell is carrying.

And for the record, it’s  A LOT.

the iron in a red blood cell

An average red blood cell has 280 million molecules of haemoglobin.  And one haemoblogin has 4 heme groups and there is a iron molecule, buried in the centre of each heme group.  So we’re talking about over 1 billion iron atoms per red blood cell.  And millions of red blood cells are being “euthanized’ per minute.

The macrophages gather it all up and make it available for recycling.

Assuming the ferriportin pump is functioning.  When it’s not, they hold onto it – this leads to systemic shortages.

Keeping iron levels in check

Now you might be thinking, why would hepcidin deliberately keep iron levels low ?

Iron is a good thing !

But too much of  a good thing is a bad thing.

This is particularly true, when there is a possibility of a microbial invasion.  To go forth and multiply, bacteria need iron.   They will beg, borrow or steal it.

Hepcidin KNOWS this, so he deliberately keeps iron out of their reach.

iron supply versus demand

Which is why hepcidin levels are typically high during an infection or if there is inflammation.

But, it is a fine balance…..

Hepcidin the manager

Hepcidin practices just in time management.   He  makes  sure the iron is made available,  only when it is needed.   Because hepcidin understands life exists on the interface of too much and too little iron.

When you’re insulin resistant, hepcidin levels are UP.  This is not an accident, it is strategic.

low grade inflammation increases hepcidin

But over time, body iron stores increase, unfortunately this  stored iron is not accessible.

body iron stores

Clearly,  trying to fix the problem by  consuming extra iron,  is NOT THE SOLUTION.

You’re NOT SHORT OF IRON !

The shortage is an “apparent” shortage…..

In fact, in the long run, it can aggravate the situation.  Iron overload is associated with lots of chronic diseases, among them type 2 diabetes, Alzheimer’s and liver failure.

Rein in hepcidin

You’ve got to lower the  hepcidin.   If you understand the biology, this turns out to be easier than you might think………..

Watch on YouTube

REIN IN INSULIN.

For tips and strategies, to help you do this, download the WILLPOWER REPORT, it’ free.

Relationship between Serum Levels of Body Iron Parameters and Insulin Resistance and Metabolic Syndrome in Korean Children.  Osong Public Health Res Perspect (2014) 5(4) : 204e210.  Hye-Ja Lee, Han Byul Jang, Ji Eun Park, Kyung-Hee Park,  Jae Heon Kang, Sang Ick Park, Jihyun Song.

Regulation of the Iron Homeostatic Hormone  Hepcidin. Adv Nutr (2017) 8:126–36.  Veena Sangkhae and Elizabeta Nemeth

Iron deficiency beyond erythropoiesis: should we  be concerned? Current Medical Research and Opinion (2018) 34(1): 81–93.  Khaled M. Musallam & Ali T. Taher.

Further reading

siderocalin hiding th iron

To avoid UTIs you need to shore up your body’s defences

A urinary tract infection is definitely unpleasant. But, before you reach for the antibiotic, you might want to try something really simple.

adrenaline kicking up a storm

 When you GO POSTAL, your bacteria dispatch a letter bomb

Bacteria need iron to grow, so iron levels are ALWAYS kept low, except during STRESSFUL moments, when iron is made available……. bacteria come out to play

iron causing the pancreas to rust

Turning down an iron pump – irons out diabetes

When an iron pump in the pancreas runs full steam for too long, beta cells die and diabetes begins. Turning the pump down, is enough to stop diabetes.

Want to discover more ways to create BETTER BODY CHEMISTRY ?

Posted in IR | Tagged anaemia, anemia, enterocytes, ferriportin, hepcidin, insulin resistance, iron, iron deficiency, macrophages, red blood cells

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