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The Cephalic Phase of Insulin Release

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Whenever you eat food, your body produces hormones like insulin to help break that food down and use it as energy.

But did you know that the mere sight of food can also trigger an insulin response?

Let’s talk about an interesting phenomenon known as the cephalic phase of insulin release, and why it’s important, especially if you have problems with snacking.

What is insulin?

Insulin is a hormone produced by beta cells in the pancreas, which plays a crucial role in regulating blood sugar levels in the body. Its primary function is to facilitate the uptake and utilization of glucose by various cells and tissues.

When you consume carbohydrates, they are broken down into glucose, which enters the bloodstream. As the blood glucose levels rise, the pancreas detects this increase and releases insulin into the bloodstream. Insulin acts as a signal to notify cells in the liver, muscle, and adipose tissue to absorb glucose from the blood.

What does it do?

Insulin performs several key functions in the body:

  • Glucose Uptake: Insulin binds to receptors on the cell surface, allowing glucose to enter the cells. It stimulates the transport of glucose transporters (GLUT4) to the cell membrane, increasing glucose uptake.
  • Glycogen Synthesis: Once inside the liver and muscle cells, glucose is converted into glycogen through a process called glycogenesis. Insulin promotes glycogen synthesis, helping to store glucose for later use.
  • Inhibition of Gluconeogenesis: Insulin suppresses the production of glucose by the liver through a process known as gluconeogenesis. This helps prevent excess glucose release into the bloodstream.
  • Protein Synthesis: Insulin stimulates protein synthesis, supporting the growth and repair of tissues throughout the body.
  • Lipid Storage: Insulin promotes the storage of excess glucose as fat in adipose tissue, aiding in lipid synthesis and inhibiting fat breakdown.

What can trigger it?

Insulin release is triggered by elevated blood glucose levels, but other factors can also influence its secretion. These include:

  • Food Intake: The consumption of carbohydrates, especially those that raise blood sugar quickly (high glycemic index), triggers a stronger insulin response. Proteins and fats can also cause a moderate insulin release, although to a lesser extent.
  • Hormones: Some hormones, such as glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP), released from the gut after a meal, stimulate insulin secretion. Conversely, hormones like glucagon and epinephrine have the opposite effect, inhibiting insulin release.
  • Blood Amino Acid Levels: Elevated levels of certain amino acids in the blood, especially leucine, can stimulate insulin secretion.
  • Neural Inputs: Nervous system signals, particularly from the parasympathetic branch, can stimulate insulin secretion. For example, the sight, smell, or taste of food can trigger a release of insulin even before eating.

Neural vs Regular insulin release

Insulin is a hormone that helps regulate our blood sugar levels. Normally, insulin is released when we eat food. However, there’s another lesser-known way that insulin can be released even before we start eating, just by seeing or smelling food.

This early release of insulin is called the cephalic phase of insulin release (CPIR). So, what makes this cephalic phase different from the regular release of insulin?

CPIR-vs-normal-insulin-release
Cephalic phase vs Regular phase insulin release.

Firstly, the CPIR can be triggered by just the sight and smell of food, whereas the regular release only happens when we actually eat. The CPIR starts in the brain, which then activates the vagus nerve, signaling the pancreas to release insulin.

In contrast, the regular release of insulin begins when glucose from the meal directly stimulates receptors on the pancreas, right in the gut.

The CPIR acts much faster than the regular phase, reaching its peak within 2-5 minutes of being triggered, while the regular phase can take 20-60 minutes after a meal to reach its peak.

However, the CPIR releases a smaller amount of insulin overall compared to the regular release.

Moreover, the CPIR primarily targets the liver, whereas the regular release of insulin affects the whole body.

In summary, insulin is not only released when we eat but can also be triggered by the anticipation of food. This early release, known as the cephalic phase of insulin release, starts in the brain and acts quickly but releases less insulin compared to the regular phase. While the regular release affects the entire body, the cephalic phase primarily targets the liver.

What CPIR does?

This CPIR phase occurs even before we start eating, accounting for a small portion, around 1-3%, of the total insulin response.

But what exactly does the CPIR do in our bodies? Well, it’s believed that this early release of insulin helps regulate glucose control. It prepares our bodies to absorb sugar and energy ahead of the actual meal, giving us a head start.

Researchers conducted experiments on mice to understand the importance of CPIR. They bypassed the mice’s mouths and directly fed glucose into their stomachs, preventing them from tasting or anticipating the food. As a result, these mice lost the CPIR response.

Interestingly, these mice experienced glucose intolerance, meaning they had difficulty effectively absorbing sugars from their meals. This finding suggests that the CPIR plays a crucial role in maintaining healthy blood sugar levels.

In humans, it has been observed that individuals with a weakened CPIR have an overall weaker insulin response and struggle with blood sugar control. Recent research has even revealed that obese individuals tend to have a muted or weakened CPIR. This could be one explanation as to why they often face challenges with glucose control and find it easier to gain weight compared to non-obese individuals.

In summary, the CPIR is an early release of insulin that occurs before we eat. It helps prepare our bodies for incoming glucose and plays a role in glucose control. Impaired CPIR may contribute to difficulties in managing blood sugar levels and weight gain, particularly in obese individuals.

Problems with snacking

However, there are potential downsides to the cephalic phase of insulin release (CPIR). While it can be beneficial in helping us absorb the food we’re about to eat, what happens if we’re trying to avoid eating something?

You see, insulin does more than just facilitate food absorption. It can also stimulate hunger and increase our desire to eat.

These additional effects of CPIR can become problematic, especially when we don’t actually intend to eat any food.

Let me illustrate this with an example. Imagine you’re trying to reduce your late-night snacking. As you walk past the kitchen on your way to the bathroom, you notice a bag of chips. Suddenly, your brain triggers a CPIR response, and within a few minutes, your pancreas starts producing a small amount of insulin.

This release of insulin is going to intensify your appetite and prepare your body to potentially eat those chips later, even though you haven’t actually indulged in them and genuinely don’t want to. Now, all you can think about are those chips. The mere sight and the thought of those conveniently available chips have triggered a physiological response that is typically reserved for actual eating.

How to control snacking

This is why it’s often recommended to remove all unhealthy snacks from your home if you’re trying to control your snacking habits.

Simply hiding snacks out of sight may not be sufficient because the mere thought of having access to them can trigger the cephalic phase of insulin release (CPIR).

Resisting temptation becomes much more challenging when the temptation is constantly present and readily available, such as having snacks in your room or home.

On the other hand, resisting temptation becomes easier when the temptation is not readily available or requires effort to access. For example, if you have to go to the store to buy snacks, it gives you an extra barrier. However, even with the convenience of online shopping, you might need to reduce the frequency of browsing websites like Amazon to further minimize the temptation.

Successfully avoiding unhealthy snacking goes beyond simply deciding not to eat. There are strategies you can employ to make it easier for yourself or create obstacles that make it more difficult.

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Citations

A.B. Steffens. Influence of the oral cavity on insulin release in the rat. American Journal of Physiology-Legacy Content, 230 (1976), pp. 1411-1415

Ahrén B, Holst JJ (2001) The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 50:1030–1038

Del Prato S, Tiengo A (2001) The importance of first-phase insulin secretion: implications for the therapy of type 2 diabetes mellitus. Diabetes Metab Res Rev 17:164–174

Eliasson B, Rawshani A, Axelsen M, Hammarstedt A, Smith U. Cephalic phase of insulin secretion in response to a meal is unrelated to family history of type 2 diabetes. PLoS One. 2017 Mar 13;12(3):e0173654. doi: 10.1371/journal.pone.0173654. PMID: 28288176; PMCID: PMC5348013.

Gilon P, Henquin J-C (2001) Mechanisms and physiological significance of the cholinergic control of pancreatic β-cell function. Endocr Rev 22:565–604

Güemes A, Herrero P, Bondia J, Georgiou P. Modeling the effect of the cephalic phase of insulin secretion on glucose metabolism. Med Biol Eng Comput. 2019;57(6):1173-1186. doi:10.1007/s11517-019-01950-x

J. Louis-Sylvestre. Preabsorptive insulin release and hypoglycemia in rats. American Journal of Physiology-Legacy Content, 230 (1976), pp. 56-60

Pullicin AJ, Glendinning JI, Lim J. Cephalic phase insulin release: A review of its mechanistic basis and variability in humans. Physiol Behav. 2021;239:113514. doi:10.1016/j.physbeh.2021.113514

Rodin J. Insulin levels, hunger, and food intake: an example of feedback loops in body weight regulation. Health Psychol. 1985;4(1):1-24. doi:10.1037//0278-6133.4.1.1

Teff KL (2011) How neural mediation of anticipatory and compensatory insulin release helps us tolerate food. Physiol Behav 103:44–50

University of Basel. “The mere sight of a meal triggers an inflammatory response in the brain.” ScienceDaily. ScienceDaily, 30 June 2022. www.sciencedaily.com/releases/2022/06/220630083255.htm.

Wiedemann SJ, Rachid L, Illigens B, Böni-Schnetzler M, Donath MY. Evidence for cephalic phase insulin release in humans: A systematic review and meta-analysis. Appetite. 2020;155:104792. doi:10.1016/j.appet.2020.104792

Wiedemann SJ, Trimigliozzi K, Dror E, et al. The cephalic phase of insulin release is modulated by IL-1β. Cell Metab. 2022;34(7):991-1003.e6. doi:10.1016/j.cmet.2022.06.001


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