Improving sugar control requires better pipes NOT MORE INSULIN

acetylcholine offering a flower as insulin knocks on door

In people with poorer glycemic control the blood is not flowing as well – contributing to this problem is a collapse in the blood network infrastructure. 


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Improving sugar levels requires better pipes

Insulin knocking on door with acetylcholine offering a flower

In people with poorer glycemic control the blood is not flowing as well – contributing to this problem is a collapse in the blood network infrastructure.

Whenever a grocery delivery  comes in…………..

It MUST be processed and cleared, QUICKLY.

Now doing this is a TEAM EFFORT.

The liver is particularly important :  it uses the basic ingredients to whip up batches of this, that and the other.  And it depends on insulin to help keep things running smoothly.

Insulin making grocery deliveries

Now truth be told, insulin “worries” about pretty much every nutrient, but getting the sugar delivered is his priority.

So where is the sugar delivered to ?

Well all cells need it, some more than others.  But, there only a few actually store it and  insulin manages the distribution process.

The biggest sugar cupboards are the muscles.

In fact 80 % of the sugar that arrives with dinner is taken up by muscles.  So deliveries to the muscles are RATHER IMPORTANT.

Muscles receiving their sugar hit

In response to insulin’s signalling, muscles  put up their GLUT4 gates and let the sugar in.  Some of the sugar they burn to do “muscle things”, but if they are currently enjoying down time, they will bring the sugar in and assemble it, into glycogen.

The glycogen will be safely stored away until it is needed.

Muscle drinking coffee surrounded by glycogen flowers

The challenges of insulin resistance

Now when you’re metabolically challenged, this process doesn’t always go according to script.

A multitude of issues arise, the end result, the gates are slow to go up and the sugar keeps circulating.  When it hangs around for longer, you experience a sugar spike.  And in the long run, sugar spikes are damaging.

The moving parts

Now there are lots of moving parts to getting the sugar delivered, all of which are not working optimally when you’re metabolically challenged.

three parts to glycemic response

Insulin/the pancreas is usually blamed.

But, this is not the only problem.  This is what a group of researchers based in  Iowa City, discovered when they took advantage of new technology to take a look at what was going on inside of forearm muscles, on a day to day basis.

Peeking inside arm muscles

They used a Doppler ultrasound, to assess how responsive the blood vessels in the forearm were to signals to dilate.  The technique allows them to calculate the forearm vascular conductance (FVC for short), which is a measure of how easily the blood moves through.

The higher the number, the better.

The signal they used was acetylcholine,  not nitric oxide,  this is important.  Both are substances that help blood vessels to dilate.

blood vessel responding to vasodilators  Nitric oxide is intimately associated with insulin and blood flow, acetylcholine NOT SO MUCH.

Acetylcholine binds to muscarinic receptors.

Acetylcholine on the prowl

These special receptors are located on all the major organs, in the brain, as well as on blood vessel walls.

receptors on blood vessel wall

So what happens when acetylcholine is whooshing through the forearm, reflects the architecture of the blood network running through the forearm muscles.

The comings and goings of acetylcholine

Now for the record, acetylcholine would be “whooshing” around after dinner.  Acetylcholine is the neurotransmitter that drives the parasympathetic side of the nervous system.  It is released when the vagus nerve is stimulated

This happens when you’re falling asleep, but it also happens every time you eat.

In fact, the way  students remember what this side of  the autonomic nervous system does, is with the acronym REST and DIGEST.

Now the vasodilation that happens with dinner happens DEEP inside the organs.

acetylcholine climbing onto muscarinic receptor

It complements the nitric oxide dependent vasodilation and helps to  facilitate  grocery (and insulin) deliveries.

Infusing acetylcholine

Our team infused acetylcholine into the forearms of  44 people.

30 were officially diabetic and 14 were not.

All were heavier than ideal and the level of glycemic control varied from good to problematic.  The team used the HbA1c level of 7, as the cut off point for good/bad control.  Click here to learn more about HbA1c.

Linking blood flow to glycemic control

The team found, that people with poor glycemic control, had significantly poorer blood flow in their forearm.  Below you can see the result.

Graph showing FVC in diabetics with good versus bad glycemic control

Increases in forearm vascular conductance (FVC, i.e.,microvascular endothelial function) during acetylcholine infusion at 4.0  ?g/dl forearm volume/min. © 2021 Joshua M. Bock et al

And when they plotted individual values, they generated this scatter plot.   In this graph, only those people with a diagnosis of diabetes have been plotted.  The black dots are those considered to be well controlled i.e. HbA1c is < 7, the open dots are considered to be poorly controlled i.e. HbA1c > 7.

Scatter plot of FVC versus HbA1c

Scatter plots showing increases in forearm vascular conductance (FVC, i.e., microvascular endothelial function) during acetylcholine infusion at 4.0 ?g/dl forearm volume/min and HbA1c.  © 2021 Joshua M. Bock et al

The pattern is clear.

In people with poorer glycemic control the blood is not flowing as well.

Good delivery is essential

Poor glycemic control is not just an insulin production problem……..

Insulin is having problems with deliveries.

This research hints that good glycemic control requires you to get the blood flowing.  You need to get the signalling working, but you also need to be creating the infrastructure.

How do you do this ?

The blood vessel infrastructure, depends on creating signals that spark sustainable blood vessel creation and maintenance, in a process known as angiogenesis.  Interestingly enough, the trigger for angiogenesis  is oxygen shortages, the technical term for this is hypoxia.

You need transient oxygen shortages.

Long term oxygen shortages, do just the opposite…………they result in blood vessel loss (regression).

And this is what tends to happen in insulin resistance, thanks to the balance between insulin and C-peptide, being “off”, continuous low level hypoxia follows.  Watch this video to learn more.

Turning the tide

The good news is, you can create transient hypoxia – there are quite a few ways to do, the classic way is through exercise.

Squeezing, stretching and holding are all moves that build microvasculature.

But, there are other ways to do this

  • Playing high i.e. spending time at a high altitude
  • Blood vessel torture

The last one is one of my favourite “hacks” – it’s perfect if you are a couch potato.  Watch this video to learn more.

Improve glycemic control

If you’re struggling to keep your sugar levels in check, you need to cut insulin some slack and  work on the pipelines, so deliveries are improved.

This is not something your diabetes meds are doing.

They’re typically trying to whip the pancreas into shape, so more insulin is released.  But more insulin making sugar deliveries,  is of limited benefit, if the insulin that is unleashed has nowhere to go.  Make infrastructure development part of your strategies.

And then………………. use a little biology, to get the pipes you do have, working optimally.  Visit this library page to learn more.

advert to improve deliveries library page

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Glycemic management is inversely related to skeletal muscle microvascular endothelial function in patients with type 2 diabetes. Physiological Reports. (2021) 9:e14764.   Joshua M. Bock, William E. Hughes, Kenichi Ueda, Andrew J. Feider, Satoshi Hanada, Darren P. Casey

Risk of postprandial insulin resistance: The liver/vagus rapport. Rev Endocr Metab Disord. (2014)  15(1): 67–77.  Maria Paula Macedo, Inês S. Lima, Joana M. Gaspar, Ricardo A Afonso, Rita S. Patarrão, Young-Bum Kim and Rogério T Ribeiro. /symple_box]

Further reading


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Author: Taylor Payne