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Selenoprotein P in insulin resistance

Posted by Dr Sandy on in IR | 453 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.

Selenoprotein P when you’re insulin resistant

If you’re insulin resistant,  selenoprotein P or SEPP1  for short, is  typically up.

Now selenoprotein P, is  one of 25 proteins in the body, that contains selenium.  The selenoproteins have a wide range of functions :

  • they’re involved in thyroid hormone metabolism,
  • they are part of your anti-oxidant defence system,
  • they do redox signalling and
  • they also help with protein folding, in the endoplasmic reticulum.

NOTE :  There are a few, “we” still don’t have a clue, what they do

SEPP1’S  claim to fame, it is the protein tasked with transporting the selenium coming in, to the rest of the body, allowing every cell in the body, to make the selenoproteins, it needs.

the selenoprotein family

Unlike  other selenoproteins, which have one selenium atom, SEPP1 has 10 !

 So it’s up, isn’t this a good thing ?

After all, selenium is an essential nutrient.  And when you don’t have enough, you can be in all sorts of trouble, because the BIG job of selenium, is to co-ordinate the anti-oxidant defences.

And since metabolic troubles are linked to oxidative stress….

More MUST be BETTER !

In fact, supplementing with selenium is ENCOURAGED, as a strategy to deal with metabolic troubles.

selenium supplements for diabetics

Not so fast – more is a problem

But, if you read the fine print, you’ll find that selenium supplementation, ACTUALLY increases the risk of type 2 diabetes. Both in animals and in humans.  Ouch !

graph showing incidence of type 2 diabetes when taking selenium supplements

And too much SEPP1 has something to do with it……

Selenoprotein P is diabetogenic

It turns out, when selenoprotein P is injected into mice – they become diabetic.

It seems that elevated levels, disturb the functioning of the pancreatic beta cells and inhibit insulin secretion.

So why is it up ?

The selenoprotein P “on” switch

Well, no one knows for sure…..what is known, a rise in glucose, kickstarts the pancreas to secret insulin and the liver, to secrete Selenoprotein P.  The secreted SEPP1, probably helps put away the groceries “safely”, by among other things, locking up any heavy metals, that might have come in, with the meal.

selenoprotein P locking down heavy metals

The actual selenium delivery, takes hours to be assimilated – so it’s highly unlikely, selenium per se, is helping with “deliveries”.

The selenoprotein P “off” switch

Insulin is meant to suppress sepp1 production by the liver.  Unfortunately, when the liver is insulin resistant, it ignores insulin, so the off switch is “faulty”.

So high sepp1, is a reflection of BAD BODY CHEMISTRY.

Selenoprotein P tracks with selenium

But, sepp1 levels also respond to selenium levels.  And the more selenium you’re consuming, the higher the levels, rise, up to a point.  Basically what happens, the selenium you eat, comes into the body, via the liver.

The liver then makes the decision, whether to process it, or dump it.

the liver processing dietary selenium

NOTE : Dumping it, is work, but it is do-able, unlike iron, which once it’s in, it’s IN.  Unfortunately, dumping only happens, when levels are VERY high, which is why SEPP1 levels, rise,  with increased selenium consumption. 

So how much selenium do you need ? 

Well the  amount of selenium recommended is typically 55 ug/day, although the exact amount varies, depending on where you live.   Authorities don’t recommend more than 400 ug/day, and a dose of 700 ug/day, is considered toxic.

NOTE :  Selenium supplements often contain 200 ug / tablet.

 So is it hard to get 55 ug/day ? 

The short answer is NO…..

Selenium is considered to be an abundant element, it’s found in soil, water and the air we breath.

the availability of selenium depends on soil levels

  • Plants don’t actually use it, but if it is there, they’ll take it up, exactly how much they take up, is directly proportional to selenium soil levels, with a few exceptions.  The most notable one, being Brazil nuts.  These guys,  concentrate selenium, so a single nut, could give you, your full day supply.
  • Animals, get their selenium, when they eat the plants.  And if they don’t get enough, because selenium levels in the soil are low, they run into trouble.
  • For humans to run into trouble, they need to be living somewhere, where the selenium content of soil, is exceptionally low.

And NO ONE cares……

Selenium levels are carefully managed

There are a few places in the world, where this does happen, but it is highly unlikely, you’re living there.  Today, selenium is ACTIVELY managed, across the food chain.

It’s added to soil, it’s added to animal feed, it’s added to human food and you find it in multivitamins and supplements.

img-8

Odds are you’re getting enough………….. MAYBE MORE THAN ENOUGH !

Manage your SEPP1 levels

If you’re metabolically challenged, you want to keep your sepp1 levels, in check. There are two ways to do this :

  • Work at improving your insulin sensitivity – download the free, WILLPOWER REPORT, to learn more
  • Be weary of loading up on EXTRA selenium.

Here are some of the references, I’ve used, to tell the selenoprotein P story.  Selenoprotein P is just one of hundreds of chemicals in the body that are amiss when you’re suffering from metabolic syndrome.    To learn more about some of the other players, go to our “Ups and Downs” of Insulin Resistance series.

Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes :  A Randomized Trial.  Ann Intern Med. (2007) 147:217-223.  Saverio Stranges, James R. Marshall, Raj Natarajan, Richard P. Donahue,  Maurizio Trevisan, Gerald F. Combs, Francesco P. Cappuccio,  Antonio Ceriello, and Mary E. Reid.

Selenium deficiency risk predicted to increase under future climate change.  PNAS (2017)  114 (11) : 2848–2853.  Gerrad D. Jones, Boris Droz, Peter Greve, Pia Gottschalk, Deyan Poffet, Steve P. McGrath, Sonia I. Seneviratne, Pete Smith, and Lenny H. E. Winkel

Selenoprotein P as a significant regulator of pancreatic beta cell function.  J Biochem. (2019)  pii: mvz061.  Yoshiro Saito

A Liver-Derived Secretory Protein, Selenoprotein P, Causes Insulin Resistance.  Cell Metab. (2010) 12(5):483-95.  Hirofumi Misu,Toshinari Takamura, Hiroaki Takayama, Hiroto Hayashi, Naoto Matsuzawa-Nagata,  Seiichiro Kurita, Kazuhide Ishikura, Hitoshi Ando, Yumie Takeshita, Tsuguhito Ota, Masaru Sakurai, Tatsuya Yamashita, Eishiro Mizukoshi, Taro Yamashita, Masao Honda, Ken-ichi Miyamoto, Tetsuya Kubota, Naoto Kubota, Takashi Kadowaki, Han-Jong Kim, In-kyu Lee, Yasuhiko Minokoshi, Yoshiro Saito, Kazuhiko Takahashi, Yoshihiro Yamada, Nobuyuki Takakura, and Shuichi Kaneko

Selenium–Fascinating Microelement, Properties and Sources in Food.  Molecules. 2019 24(7). pii: E1298.  Marek Kieliszek.

Selenium and human health: witnessing a Copernican revolution?  J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. (2015) 33(3):328-68. Ewa Jablonska & Marco Vinceti. 

Further reading

iodine stuck on the outside

If your health gets an F grade, check your water isn’t full of fluoride

Hypothyroidism is on the rise. Why ? Researchers suspect it has something to do with the water we’re drinking. It seems too much fluoride taxes the thyroid.

ROS guard being kept on his toes

Anti-oxidants don’t mop up free radicals, they poison cells

We’ve been told, anti-oxidants mop up free radicals. They might do this in a test tube, they don’t do it in your body, in your body they release free radicals.

fish taking out mercury

The advice to avoid fish during pregnancy is a little fishy

Women eating lots of fish during pregnancy, may pick up more mercury, but their kids are not at a higher risk of behavioural problems

 

Want to discover more ways to create BETTER BODY CHEMISTRY ?

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Posted in IR | Tagged anti-oxidant, beta cells, diabetes, diabetogenic, insulin, insulin resistance, liver, metabolic syndrome, pancreas, selenium, selenoprotein P

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