Evidence Based This post has 37 references
4.2 /5

22 Low Insulin Causes in Regular Carb Consumers

Written by Joe Cohen, BS | Last updated:

Do you have problems gaining weight? Have higher blood sugar than you are supposed to give your diet? At risk for type 2 diabetes?

If yes, then this post applies to you.

What is Insulin?

There’s a very strong correlation between being overweight and insulin levels because insulin creates fat cells.

But some people in the modern environment naturally have lower insulin levels, even if they don’t take care to reduce carbohydrate consumption.

These people with low insulin complain to me that they can’t gain weight.

Having inadequate insulin secretion is also a cause of type 2 diabetes (together with insulin resistance).

So while you might weigh less, you’ll have higher blood sugar levels and be at a higher risk for type 2 diabetes.

Insulin forces artery wall muscles to relax, thereby increasing blood flow, especially in micro-arteries. A lack of insulin reduces flow. In the thin people I deal with, they often feel cold. One of the many reasons is because of low insulin, which reduces blood flow.

This post is to give you biological reasons that may contribute to lower insulin secretion.

I’ve checked my insulin levels twice and both times they were lower than 2, which is extremely low. The thin clients that checked also had low insulin.

1) Lower Carb and Protein Consumption

The most obvious cause of low or high insulin is your carbohydrate consumption and secondarily your protein consumption. Both stimulate insulin release.

But this post focuses on people with lower insulin if they’re not on a very low carb or ketogenic diet.

This post is mainly concerned about two people with the same levels of carb and protein consumption: why do their insulin levels differ?

2) Low ATP From Poorly Functioning Mitochondria

High glucose levels normally increase ATP levels, which ends up releasing insulin [1].

But if your mitochondria aren’t producing enough ATP, insulin doesn’t get secreted as well.

3) Low cyclic AMP

cAMP is a molecule that is an important second messenger for cellular communication.

The chief role of cyclic AMP in several tissues seems to be to facilitate or promote the mobilization of glucose and fatty acid reserves.

Cyclic AMP has so many roles in the body, one of which is increasing gut flow [2], which people often have a problem with.

Cyclic AMP also promotes the release of insulin from pancreatic beta cells [3].

4) Low cyclic GMP

Like cAMP, cGMP is an important second messenger for cellular communication.

cGMP helps blood vessels, lungs, insulin secretion, and gut flow [4].

cGMP also helps insulin secretion [5]

Not getting enough sun will cause lower nitric oxide, which will lead to lower insulin release. People with low insulin don’t get enough full body sun.

5) Oxidative Stress

Free radicals cause pancreatic beta cells to malfunction and decrease insulin release [6].

Diseases like type 2 diabetes are caused by oxidative stress.

6) Circadian Dysrhythmia

People with low insulin almost always have circadian rhythm problems. Both problems are caused by lower BMAL1.

Mice deficient in a circadian gene (Bmal1) had defects in insulin secretion, both at base levels and in response to glucose stimulation. These mice were highly susceptible to diabetes [7].

BMAL1 increases the Nrf2 antioxidant protein, which decreases oxidative stress in the pancreatic beta cells [6].

In mice, a deficiency of BMAL1 leads to increased ROS levels in several tissues [8], which is an issue my clients deal with.

See circadian rhythm tips to fix this issue.

7) Lower Vagus Nerve Stimulation

Vagus stimulation has anti-anxiety and anti-depressant effects. People with anxiety very often have lower vagus activation and higher HRV.

Lower vagus activation means less insulin secretion because the vagus nerve is what connects the hypothalamus to the pancreas to tell it to release insulin [9].

Celiac vagus removal decreased insulin secretion and food intake. The celiac branch takes signals from the brain and relays it to the pancreas [10].

8) Adrenaline

An overactive nervous system is the cause of a lot of health issues that I see people have. See some of the negative effects of stress.

Adrenaline and noradrenaline, through ADRA2A receptors, inhibit insulin release from the pancreas [11].

Also, they cause a short-lived increase in blood pressure, but a long term decrease in blood pressure. They also cause decreased gut flow, sedation, and thicker blood (platelet aggregation) [11].

These are all symptoms that are more common in people I see who have lower insulin.

9) Low Oxygen/Hypoxia

I’ve spoken about how low oxygen is a common problem in people.

Hypoxia reduces blood insulin [12].

When you’re hypoxic, this will cause you to have lower ATP, lower cAMP, and loss of cellular calcium oscillations, which are necessary for CRH to stimulate insulin and insulin production in general [12].

People with bad blood flow, indicated by cold hands and feet, will suffer from lower oxygen in certain tissue – such as the pancreas.

Read the linked post to understand why you may be hypoxic.

10) 5HT2C Receptor Activation

The 5HT2C receptor shuts down appetite [13], causes depression [14], anxiety [14] and less insulin release [15].

When given an antagonist of the 5HT2C receptor, people with CFS reported less perceived fatigue [16], which might implicate this receptor in fatigue as well.

Activation of this receptor is involved in the problems people deal with who also have lower insulin.

The receptor is increased by inflammation [14], and inflammation can also cause fatigue by shutting down orexin.

Curcumin‘s anti-depressant effect may work in part via the 5HT2C receptor [17].

Estradiol decreases these receptors in the ventral hippocampus (while increasing the 5HT2A receptors) [18].

11) Lower Vitamin D Receptor Activation

People I see often have problems with the vitamin D receptor, usually because it’s blocked by some pathogen [19].

The VDR binds with RXRa to produce insulin, which will be lower if the VDR (or RXR) isn’t working well.

12) Lower Liver X Receptors (LXRs)

People I deal with often have lower detox ability, likely in part mediated by lower liver X receptors.

The liver X receptors (LXRs)-α and -β play a crucial role in the control of insulin production and secretion. People with certain polymorphisms in LXR genes show reduced insulin secretion [20].

13) Osteocalcin

Osteocalcin is a protein released by bone cells to create new bone.

Osteocalcin acts as a hormone in the body, causing beta cells in the pancreas to release more insulin, and at the same time directing fat cells to release the hormone adiponectin, which increases sensitivity to insulin [21].

Osteocalcin acts on Leydig cells of the testis to stimulate testosterone biosynthesis and therefore affect male fertility [22].

Osteocalcin synthesis is dependent on vitamin K [22].

A lot of the people I see that have lower insulin also have lower testosterone and bone density. Osteocalcin is a link with these three issues.

14) High Hydrogen Sulfide

We create hydrogen sulfide through cysteine. The effects are lower insulin [23] and lower blood pressure [24].

It also seems that people with IBS-C produce more hydrogen sulfide (H2S) [25], which are the people who are more likely to have problems with lower insulin secretion.

You want to have this compound balanced. It has a host of benefits. It increases glutathione [26], learning (LTP), libido, protects the heart and the gut while lowering inflammation (in most tissues) [27], homocysteine, diabetes, asthma, etc. [28].

While NAC and garlic seem to increase hydrogen sulfide, they increase glutathione, which combines with hydrogen sulfide to become GSSH, a harmless product [29].

The cluster of symptoms that I see (low insulin, low blood pressure, and IBS-C) make hydrogen sulfide a contributing factor for some.

15) Lower Vasopressin

Vasopressin cause insulin release in mice [30].

My clients usually have low vasopressin, which causes problems retaining water [30].

16) Lower VIP

VIP is an anti-inflammatory peptide and people with chronic inflammatory health issues often have lower VIP.

VIP stimulates insulin and glucagon secretion [31].

Glycine increases VIP [32].

17) Higher Cortisol

Cortisol decreases insulin secretion and increases insulin resistance [33].

People I see tend to have higher cortisol.

18) Lower SIRT4

Lower Sirtuins and sirtuin activity is a common problem in people with fatigue and chronic health issues.

Glutamate Dehydrogenase (GDH) is important in insulin-producing pancreatic β cells. Beta cells secrete insulin in response to an increase in the ATP: ADP ratio, and, as amino acids are broken down by GDH into α-ketoglutarate, this ratio rises and more insulin is secreted. SIRT4 is necessary to regulate the metabolism of amino acids as a method of controlling insulin secretion [34].

GDH is activated by ADP and BCAA’s like leucine [34].

GDH is decreased by excess Glutamate, which is a common problem in people with chronic fatigue [34].


The reason these are in the other category is that they don’t fit the constellation of other symptoms I see in people with low insulin. But they still affect insulin secretion.

19) Ghrelin studies on insulin release are all over the map, but it seems like they decrease insulin release [35]. So higher ghrelin would be a cause of lower insulin.

20) Secretin inhibits insulin release [31]. So higher secretin would be a cause of lower insulin.

21) RXR has a suppressive effect on insulin secretion [36].

22) The stress hormone CRH (via CRHR1) causes insulin secretion, but it cannot do this if there is low oxygen in tissues [12]. This effect is also potentiated by [37].

The people I deal with generally have too much CRH, but they also have low oxygen delivery to tissues and low vasopressin. Some people with depression can have lower CRH.


About the Author

Joe Cohen, BS

Joe Cohen, BS

Joe Cohen flipped the script on conventional and alternative medicine…and it worked. Growing up, he suffered from inflammation, brain fog, fatigue, digestive problems, insomnia, anxiety, and other issues that were poorly understood in traditional healthcare. Frustrated by the lack of good information and tools, Joe decided to embark on a learning journey to decode his DNA and track his biomarkers in search of better health. Through this personalized approach, he discovered his genetic weaknesses and was able to optimize his health 10X better than he ever thought was possible. Based on his own health success, he went on to found SelfDecode, the world’s first direct-to-consumer DNA analyzer & precision health tool that utilizes AI-driven polygenic risk scoring to produce accurate insights and health recommendations. Today, SelfDecode has helped over 100,000 people understand how to get healthier using their DNA and labs.
Joe is a thriving entrepreneur, with a mission of empowering people to take advantage of the precision health revolution and uncover insights from their DNA and biomarkers so that we can all feel great all of the time.


1 Star2 Stars3 Stars4 Stars5 Stars
(13 votes, average: 4.15 out of 5)

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

Leave a Reply

Your email address will not be published. Required fields are marked *

Related Articles View All