Croaking about a new way to put away sugar and improve glycemic control

isthmin offering sugars on his tongue

Insulin has just been made redundant.  Isthmin is Mother Nature’s  alternative sugar delivery system.  It does what insulin does, but only better.


Share Button

Click to listen to the audio…

Introducing Mother Nature’s alternative sugar delivery system

spotlight on isthmin a frog protein turned human adipokine

Insulin has just been made redundant. Isthmin is Mother Nature’s alternative sugar delivery system. It does what insulin does, but only better

If you’re battling to control your sugar levels….

Your insulin system IS BROKEN.

The assumption is, the only way to fix the “sugar problem”, is to fix the “insulin problem”.

And there are a range of tactics that can do this and the most appropriate tactic, will depend on what exactly IS BROKEN.

Fixing the insulin system

The simplest approach, and my go to strategy, involves sending  in less sugar, so the need for insulin is minimized.  The added advantage of this approach, is insulin levels are curtailed and this is most healthful, because many of the complications associated with diabetes are driven by high insulin i.e. high sugar levels are not the only problem.

The second, is to send in truck loads of insulin, sometimes directly, but usually the approach is to whip the beta cells into a frenzy, so there is enough insulin circulating,  to bully insulin resistant cells into compliance.   It works in the short term.

And then there are a few things in between….

The point is, the focus is always on INSULIN.

Because up until now, we have assumed INSULIN is the only hormone, responsible for sugar deliveries.

But this is biology……..

Redundancy rules

Mother Nature uses redundancy as a design principle. She frequently has a plan B, sometimes even a plan C and plan D, because redundancy is vital in “life and death” situations.

fairy godmother celebrating various possibilities

Now it’s fun to play these out.

And it is what we often do, at better body chemistry.

Let me count the ways

For example………

  • You can exercise like crazy, and get the blood flowing, creating shear stress and lots of good biology i.e. increased nitric oxide.
  • Or, you can sit in the sauna and cook,  as you cook, you get the blood flowing, creating shear stress and lots of good biology  i.e. increased nitric oxide.
  • Or, you could feed the bacteria living in your mouth, some spinach salad, the little critters will turn the nitrate into nitric oxide, once more creating some good biology.

NOTE :  To learn more about the good biology nitric oxide brings, visit the nitric oxide library page.

Exercising is ALWAYS going to be  better, but not always practical.

This redundancy principle means there is often more than one solution to a problem and sometimes our behaviours can leverage that biology.  Which brings me to, today’s story. …..

A new lever for sugar control

A team of researchers, based at Stanford University,  have recently discovered a completely independent sugar delivery system.

This makes insulin is “REDUNDANT”.

The star of this system isthmin 1.

It’s not a new chemical per se. It was first discovered in a frog’s brain in 2003.  The part of the brain it came from, was the isthmus, which is how it got its name.   It’s not a protein too many people have paid much attention to and the lack of interest, has not been because it’s a frog protein, we humans have it, in a variety of cell types.

Both as adults and as embryos.

Some of the human cell types expressing isthmin-1

In fact, the protein was seen as being important in development, until…………….it came onto the radar of the Stanford team.

A protein in search of a function

The team set about figuring out, what it was doing, in mice, using some genetic jiggery-pokery.  They created a mouse, that was not able to express the protein normally and one that produced, a little bit more than normal and the results were INTERESTING.

They found that if was an adipokine i.e. it was being actively secreted by fat cells (adipocytes).   And to their surprise, found it was able to stimulate sugar uptake in adipocytes (and muscle cells), WITHOUT INSULIN.

isthmin popping a sugar delivery into the mouth of a fat cell


Interestingly, isthmin has NO effect on sugar uptake by  liver cells.

Insulin needs isthmin

And then to make things a little more interesting, they found that without isthmin, insulin was not able to trigger adipocyte sugar uptake.

isthmin helping insulin to open insulin receptor

And this is a BIG DEAL.

Fat cells  don’t actually use sugar as their fuel source, they’re lactate burners, but sugar deliveries  get fat cells IN THE MOOD.  And when they’re IN THE MOOD, they send signal a signal to the liver, to temporarily shut up shop and stop making sugar.

NOTE :  This should happen when you eat.

The asprosin connection

We already know, asprosin is behind this messaging.   Fat cells that respond to insulin appropriately, stop producing asprosin and this signals the liver, to stop producing sugar.  Click here to learn more about asprosin.

When the liver downs tools.

The liver reacting negatively to the presence of isthmin

Sugar levels don’t spike, PERIOD.

If doesn’t matter whether  you eat a twinkie, toasted cheese sandwich or a salad, because when insulin only has to worry about the sugar that came in with dinner, he is usually quite capable of handling the situation.

It’s the NON STOP liver gluconeogenesis which creates ALL THE DIFFICULTIES.

The benefits of stopping hepatic gluconeogenesis

Since isthmin is able to facilitate  sugar uptake by fat cells, it  is part of the system that stops hepatic gluconeogenesis.  But isthmin doesn’t just signal to the liver via fat cells, the liver responds to isthmin DIRECTLY.

And the response is VERY different from how it responds to insulin.

Not just in terms of sugar production.

Insulin signals to store fat

When both sugar and insulin are around and sugar levels are freakishly high, the liver tries to help out, by turning some of the sugars into fat.  The process is called de novo lipogenesis.  But it’s a case of……………….

No good deed goes  UNPUNISHED.

The liver often ends up becoming engorged with fat.

the liver becoming engorged with fat

His anguish is felt far and wide.  Priming the pancreas to pump out more insulin – this post, shares more about the biology that drives the problematic insulin secretion.

Is this the secret to fixing the hyperinsulinemia ?

It’s like a run away fire…..

Fat stores multiply

Your problem is not just  that your sugar levels are a lot higher than ideal, so are your insulin levels (hyperinsulinemia) and you’re storing fat, EVERYWHERE.

  • In the belly (abdominal fat)
  • In your liver (fatty liver)
  • In nooks and crannies, it’s not supposed to be (ectopic fat)

Isthmin signals to  make protein

But when  isthmin is around,  the liver switches up what it does…..


Instead of opting to make fat, with the excess sugar,  it ups protein synthesis.

Contrasting the two sugar delivery systems

That makes isthmin potentially a MUCH BETTER solution to sugar problems, than insulin, because more isthmin,  will serve to put  sugar away, without creating a “FAT” problem.

Isthmin injections please

The team are excited, so am I……….

They’re thinking a block buster drug.

I’m thinking, maybe  this is a  pathway, that can be leveraged through lifestyle ?  I hope so.  Isthmin is definitely on my radar, but since pretty much NOTHING is really known about isthmin-1, it will be a while before we are able to harness the possibilities.

But it is a story of possibilities.

Mother Nature has an alternative system to make sugar deliveries and this system, seems to work to put sugars away, independently of insulin.  And preliminary data, suggests even if you are insulin resistant, this system still works..

This is a frog you want to kiss.

Share Button
Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis.  Cell Metabolism (2021) 33 : 1836–1852.  Zewen Jiang, Meng Zhao, Laetitia Voilquin,Yunshin Jung,Mari A. Aikio, Tanushi Sahai, Florence Y. Dou, Alexander M. Roche, Ivan Carcamo-Orive, Joshua W. Knowles, Martin Wabitsch, Eric A. Appel, Caitlin L. Maikawa, Joao Paulo Camporez, Gerald I. Shulman, Linus Tsai, Evan D. Rosen, Christopher D. Gardner, Bruce M. Spiegelman, and Katrin J. Svensson

Mechanisms of Feedback in the Frog Visual System. Adam Eggebrecht’s dissertation for a Doctor of Philosophy in Physics, Washington University in St. Louis, 2009.  

Further reading

Want to discover more ways to create BETTER BODY CHEMISTRY ?

Author: Taylor Payne