How to use incretins to minimize sugar spikes at dinner time

the incretin effect

The incretin effect is mediated by glucagon, making it an honorary “INCRETIN” –  so if you’re metabolically challenged, you must eat protein, along with your carbs, to keep sugar spikes in check

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How to naturally boost insulin levels at dinner time.

alpha cell playing chess with beta cellYou’re battling to keep your sugar levels in the RIGHT RANGE.

Especially after dinner.

More insulin please

Now one options to fix the problem…. is to give yourself a squirt of insulin, courtesy of  big pharma.

Ouch !  You’re afraid of needles.

A second option is to exploit the system the body uses to get an insulin boost, with dinner.  Cells lining the gut,  give the beta cells in the pancreas, a prod, encouraging them to secrete MORE insulin.

The system is called the incretin system.

Scientists first described the system years ago, when they noticed that  the body responds to glucose coming in with the food, much more vigorously, than glucose circulating in the plasma. They figured out that SOMETHING, produced in the gut,  caused insulin to be released.

The insulin releasing substance was named INCRETIN.

defining incretin

It’s now known, there are two proteins that are produced by the cells lining the gut, that enhance insulin release.

introducing GIP the cheaterGIP

The first one, produced by K cells located in the early part of the duodenum, is by far  the more influential one, it goes by the name  GIP.

This protein started out as gastric-inhibitory protein, but as more was learned, the name was “adjusted” to better reflect the role it was playing.  Currently GIP is short hand for  glucose-dependent insulinotropic polypeptide.

But GIP is a good name….for this little guy.

introducting GIP the cheater

He is a quite literally a GIP i.e. a cheater.

Turning him off and turning him on, both seem to have the same effect.  And he has a reputation for being an obesogenic hormone  Eish !


introducing GLP-1The other member of the incretin family, is GLP-1.   Here there is no ambiguity about the name, GLP-1 is derived from proglucagon and is thus referred to as a glucagon-like peptide.

NOTE : Where there is a little ambiguity in whether gut GLP-1 is all that important. Eish !   

Incretin based therapies

But when it comes to fighting type 2 diabetes,  GLP-1  is this incretin that you can get your hands on if you visit a pharmacy.   The name of the  GLP-1 based preparation  is  Exenatide  (the trade name is Byetta®) and just like insulin, it comes in the form of a subcutaneous injection.

Incretin mimetics

Okay, okay…….. it’s not actually human GLP-1 in the box, it’s a protein derived from the saliva of the Glia monster.  The name of this protein is Exendin-4, it is very similar to human GLP-1, but it sticks around for longer.

GLP-1’s half-life is under 5 minutes.

comparison between human incretin GLP-1 and exendin-4

Exendin-4 has a half-life of around 100 minutes.

NOTE :   The reason it works, is it’s around for longer – fasilatiating insulin release. 

DPP inhibitors

You can also get a script for a  gliptin e.g. sitagliptin, saxagliptin or linagliptin, these drugs also give you an incretin boost, so they’re classified as incretin mimetics.   The way these drugs work, is they distract the enzyme (dipeptidyl peptidase-4 or DPP-4 for short),  which is responsible for incretin breakdown.

gliptin bribing dipeptidyl peptidase 4 enzyme to stop biting the incretin

And this keeps the GLP-1 and GIP, around for longer than normal, prompting more insulin to be released.

the incretins happy because DPP-4 is inhibited


But I don’t want to talk about drugs……..

Naturally boost the incretin response

I want to share how you can get the incretin system, especially the GIP side of things, working for you, WITHOUT drugs.

It’s easy to do and pretty safe.

It is based on research coming out of Duke University in the USA.

Two faced GIP

Now,  I did say GIP was  a shyster….

And this holds true for who is cosies up with inside the pancreas.

He  is happy to befriend both alpha cells and beta cells, who are geographic neighbours, but are biological opponents. Well this is how they’re typically depicted.

Fraternizing with the enemy

The beta cells are the star players when it comes to glucose metabolism, since they produce insulin.   And insulin puts away the groceries, most especially glucose.

The alpha cells on the other hand produce glucagon.

And  in the metabolically challenged, glucagon is  TROUBLE with a capital T, the reason it causes the liver to produce glucose……….

So alpha cells contributes to the glucose PROBLEM.

So on paper at least………GIP  fraternizing with the enemy, creates a conundrum.

Dietary protein sparks glucagon release

Now, glucagon flies about anytime you eat protein…..

The Duke team confirmed this, when they measured the levels of glucagon, released from isolated mouse islets following exposure to glucose and  alanine (this is one of the amino acids that comes with protein foods).    In the figure below, you can see in the case of glucose, pretty much nothing happened, while alanine caused a significant squirt of glucagon to be released.

glucagon release following different treatment conditions

Relative area under the curve (AUC) for glucagon release following stimulation with different conditions.  Copyright © 2021 K. El, S. M. Gray, M. E. Capozzi et al.

GIP ups the alpha cell response

But the Duke team, took it one step further and  demonstrated that alanine was not the only chemical, able to cause a release of glucagon., see the graph above.  GIP also did this…….

In fact it was marginally better.

And if alanine and GIP were around at the same time………..glucagon levels shot into the stratosphere.

Oops !  All that glucagon is potentially a recipe for a hyperglycaemic disaster.   

Blow me down this is crazy

When the researchers did a little hocus pocus of their own, using mice that had been genetically manipulated to have no GIP receptor, on the alpha cells……

It became clear, the drama was being initiated by GIP hobnobbing with alpha cells.

Making GIP is the bad guy !

graph showing glucagon release depends on GIP receptor

Plasma glucagon levels in response to GIP + alanine injection in normal mice , compared to mice with no GIP receptor on alpha cells Copyright © 2021 K. El, S. M. Gray, M. E. Capozzi et al.

But hang on a minute, GIP is an incretin – it increases the release of insulin.   Confused ?

Don’t be, GIP is doing it’s job – it’s just doing it indirectly i.e. via the alpha cells !

Below  is the insluin response in normal islets, compared to alpha islets without a GIP receptor.  No receptor results in NO  INSULIN.

graph showing insulin response when there is or isn

Insulin secretion in response to GIP  or GIP + alanine in isolated islets.  The black shows normal isletes. The maroon shows islets with no GIP receptor on the alpha cells. Copyright © 2021 K. El, S. M. Gray, M. E. Capozzi et al.

The incretin effect is mediated by glucagon.

This makes glucagon an “INCRETIN”.

Alpha to beta cell communication

It turns out, the alpha cells are behind the incretin effect, not the intestinal cells.  The biology just got a whole lot more complicated.

It’s a headache for drug developers and text book writers….but, it’s biology you can use.

Protein rules

When you tuck into dinner or a snack, make sure it’s not exclusively made up of carbs.

You need to get your alpha cells “talking”.

Glucose alone won’t do that. In fact, a carb only meal,  typically silences the alpha cells, this is shown in the graph below.

graph showing insulin release

Glucacogn response following a glucose meal versus a mixed meal (glucose + protein)   Copyright © 2021 K. El, S. M. Gray, M. E. Capozzi et al.

And,  this has a knock on effect on how much insulin is produced.

Impact of a mixed meal on insulin

Glucacogn response following a glucose meal versus a mixed meal (glucose + protein)   Copyright © 2021 K. El, S. M. Gray, M. E. Capozzi et al.

A protein-carb combo works much better.

Obey the rule of thirds

I recommend you obey the rule of thirds…….

Include a little bit of carbs, a little bit of protein and a little bit of fat, every time you eat.  EVERYTIME !  Snacks included.  That way you trigger all the gut hormones, and get your biology working for you.

What about fruit salad ?

Fruits are healthy, but………….. they are carbs.  If you are metabolically challenged, add a hunk of cheese to that bowl of fruit, to give yourself a little protein and fat – this will help you handle “things” much better.

For more ideas on how to use food, to minimize those sugar spikes at dinner time, head on over to the “Suppressing sugar spikes” library page.  You’ll find several suggestions that will help you keep carbs on the plate, when you are metabolically challenged.

use science to keep those carbs on your dinner plate

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Repositioning the Alpha Cell in Postprandial Metabolism.  Endocrinology (2020)  161 (11) : 1–11.  Kimberley El, Megan E. Capozzi, and Jonathan E. Campbell

GIP mediates the incretin effect and glucose tolerance by dual actions on alpha cells and beta cells. Sci. Adv. (2021) 7 : eabf1948.  El, S. M. Gray, M. E. Capozzi, E. R. Knuth, E. Jin, B. Svendsen, A. Clifford, J. L. Brown, S. E. Encisco, B. M. Chazotte, K. W. Sloop, D. J. Nunez, M. J. Merrins, D. A. D’Alessio, J. E. Campbell. 

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Author: Taylor Payne