Mushroom Compounds and Incretin Hormones: GLP-1 and GIP

Mushrooms & Diabetes / Blood Sugar

17% GLP-1 boost

Dicks et al.'s 2022 randomized controlled trial found that adding 20g of oyster mushroom powder (8.1g of beta-glucans) to a single meal raised GLP-1 exposure by 17% in adults with impaired glucose tolerance, with the effect driven by gut bacterial fermentation of the mushroom's polysaccharides.

Dicks et al., European Journal of Nutrition, 2022

8.1g

beta-glucans in the serving that produced the 17% GLP-1 boost

P=0.001

statistical significance of the GLP-1 increase in the Dicks RCT

2

incretin hormones (GLP-1 and GIP) stimulated by the gut fermentation pathway beta-glucans trigger

Dicks et al., European Journal of Nutrition, 2022

View as image ↗

GLP-1 and Ozempic have become household names. Less discussed is the incretin system those drugs work within, the set of hormones that the gut naturally releases after eating to signal the pancreas to produce insulin. Mushroom compounds incretin hormones research has accelerated over the past five years, and the most specific human data is striking: in a 2022 randomized controlled crossover trial, adding oyster mushroom powder to a single meal raised the total GLP-1 exposure in people with impaired glucose tolerance by 17%, with a p-value of 0.001.^[1]

The mechanism is not the same as GLP-1 receptor agonist drugs. Mushroom compounds do not bind to the GLP-1 receptor and mimic the hormone directly. They stimulate the body's own production of GLP-1 through a pathway that runs through the gut microbiome. The difference matters both for setting realistic expectations and for understanding who is most likely to benefit.

This article explains the incretin system, maps the pathway from mushroom polysaccharides to GLP-1 and GIP secretion, covers what the 2022 and 2025 human studies actually found, and addresses the GIP angle that no competitor covers: whether mushroom compounds might stimulate both incretin hormones, the same dual target that makes tirzepatide more effective than semaglutide.

For the broader Ozempic-comparison framing and the clinical weight loss angle, see mushrooms and GLP-1: can fungi mimic the Ozempic effect?. For the pillar article on mushrooms and type 2 diabetes, start there for the species overview.

The Two Hormones That Run Your Post-Meal Metabolism

Incretins are hormones secreted by the lining of the small intestine and colon in response to food. They are the gut's way of communicating with the pancreas: after you eat, your digestive tract releases incretin hormones as nutrients are detected and absorbed, signaling the pancreas to release insulin in proportion to what just came in.

The two most important incretin hormones are GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). They do overlapping but distinct jobs.

GLP-1 is produced by L-cells, which are concentrated in the distal small intestine and colon. GLP-1 stimulates insulin secretion from the pancreas, suppresses glucagon (the hormone that raises blood glucose), slows gastric emptying so nutrients enter the bloodstream more gradually, and signals the brain that you have eaten enough. The drugs semaglutide (Ozempic, Wegovy) and liraglutide work by binding to the GLP-1 receptor and activating it directly, mimicking the hormone at much higher and more sustained levels than the body would naturally produce.

GIP is produced by K-cells, which are concentrated in the proximal small intestine (the duodenum and upper jejunum, the first segments your food reaches after the stomach). GIP also stimulates insulin secretion, and importantly, it appears to sensitize fat tissue to insulin and may directly reduce appetite in the brain. Tirzepatide (Mounjaro, Zepbound) targets both GLP-1 and GIP receptors simultaneously, which is why it tends to produce greater weight loss than semaglutide in head-to-head comparisons.

What neither hormone is, in its natural form, is something the body produces in large amounts for extended periods. The incretin effect is meal-triggered and short-lived. Both hormones are broken down within minutes by an enzyme called DPP-4. The pharmacological approach bypasses this by using drug forms that resist breakdown; the nutritional approach works by stimulating more endogenous production around meals.

The Chain From Mushroom Fiber to Incretin Release

Mushroom beta-glucans are polysaccharides: chains of glucose molecules connected by bonds that human digestive enzymes cannot break. They pass through the stomach and small intestine largely intact and arrive in the colon in a form that gut bacteria can ferment.

Ma and colleagues' 2022 systematic review in Critical Reviews in Food Science and Nutrition confirmed this pathway for edible mushroom polysaccharides: they resist digestion, reach the colon, and are fermented into short-chain fatty acids (SCFAs) by resident gut bacteria.^[3] SCFAs are small compounds produced when bacteria break down fiber. The three most important are acetate, propionate, and butyrate, and they serve as both an energy source for colon cells and as signaling molecules for the rest of the body.

The signaling step is where incretins enter the picture. The colonic L-cells that produce GLP-1 have receptors called GPR41 and GPR43 on their surface. These receptors are specifically designed to detect SCFAs. When SCFAs from mushroom fermentation bind to GPR41 and GPR43, they trigger GLP-1 secretion from L-cells into the bloodstream.

Zhao and colleagues' 2023 review in Biology mapped the complete chain in more detail: mushroom polysaccharides selectively feed beneficial gut bacteria (Lactobacillus, Bifidobacterium, Akkermansia), increasing their populations; these bacteria produce more SCFAs; the SCFAs activate GPR41/43; and the resulting GLP-1 increase is accompanied by improvements in intestinal barrier integrity and immune signaling.^[4]

The GIP picture is less directly documented for mushroom compounds. K-cells in the proximal intestine are primarily stimulated by dietary fats and glucose coming directly into contact with them. SCFAs from colon fermentation would reach K-cells after the fact. However, mushroom beta-glucans also increase the viscosity of food contents, slowing the release of nutrients and changing how quickly fats and sugars are presented to K-cells. This viscosity effect may modulate GIP secretion indirectly. The direct beta-glucan to GIP data in human studies is not yet published to the degree of the GLP-1 data.

The 17% RCT: What Dicks and Colleagues Actually Found

In 2022, Dicks and colleagues published a randomized controlled crossover trial in the European Journal of Nutrition.^[1] Twenty-two adults with impaired glucose tolerance (blood sugar higher than normal but not yet meeting the threshold for type 2 diabetes) each ate the same test meal on two separate occasions: once with 20g of oyster mushroom powder added to it, and once without. The design was double-blind and crossover, meaning each participant served as their own control.

The mushroom-fortified meal contained 8.1g of beta-glucans from the oyster mushroom powder. The result: the area under the GLP-1 curve, a measure of how much GLP-1 was circulating over the hours following the meal, was 17% higher in the mushroom condition than in control (P=0.001).

The study also found a 14% reduction in circulating non-esterified free fatty acids (NEFAs). Free fatty acids circulate in the blood after a meal and are associated with insulin resistance at high levels; the reduction suggests the oyster mushroom powder was affecting fat metabolism beyond just the incretin pathway.

The population matters for interpreting this finding. People with impaired glucose tolerance already have a dysfunctional incretin response compared to metabolically healthy adults, which is part of what makes them more prone to developing type 2 diabetes. A 17% GLP-1 boost from a food item in this population is a meaningful signal. Whether the effect would be similar in metabolically healthy people or people with established type 2 diabetes remains to be tested.

Why Your Gut Microbiome Determines How Much You Benefit

A 2025 paper by Klümpen and colleagues in Molecular Nutrition and Food Research added a critical layer to the Dicks 2022 findings.^[2] Using the same 22-participant dataset, Klümpen's team analyzed whether baseline gut microbiota composition predicted how much GLP-1 each participant gained from the mushroom meal.

The answer was yes, substantially. Participants with lower gut microbiota evenness before the meal showed significantly greater GLP-1 increases after the mushroom-fortified meal (p=0.012). The GLP-1 effect was larger in participants whose gut bacterial communities were less balanced.

The mechanistic interpretation: if beta-glucans produce GLP-1 primarily through gut fermentation and SCFA production, then having a gut microbiome that is already well-diversified and active may produce a ceiling effect: there is less room to increase SCFA production if it's already high. People with a less-balanced gut microbiome have more room to gain from an influx of fermentable fiber.

This is the honest counterpoint to the "mushroom powder raises GLP-1 by 17%" headline: the 17% is an average, and individual responses vary depending on who is eating and what state their gut bacteria are in when they eat it. Someone who already eats a very high-fiber diet and has a diverse microbiome may see a much smaller effect. Someone with poor gut microbiota diversity, which is common in people with metabolic dysregulation, may see a substantially larger effect.

Klümpen's finding suggests that mushroom beta-glucans may be most effective as a GLP-1 secretagogue, a substance that stimulates GLP-1 production, precisely in the population with metabolic dysfunction, which is also the same population where the benefit would be most clinically relevant.

Ghrelin: The Hunger Hormone Angle

GLP-1 is not the only gut hormone that mushrooms affect. Kleftaki and colleagues ran a separate RCT in 2022 in Pharmacological Research, this time using king oyster mushroom (Pleurotus eryngii) in adults with metabolically unhealthy obesity.^[5]

They measured ghrelin, the hormone produced in the stomach that rises before meals to signal hunger and falls after eating. Ghrelin suppression after a meal is one of the signals that tells you that you have eaten enough and it is time to stop. Impaired ghrelin suppression after meals is associated with overeating.

The king oyster mushroom meal produced significantly greater ghrelin suppression compared to control in the obese participants. Postprandial blood glucose was also improved, and subjective hunger and fullness scores shifted in the expected direction. This is a distinct mechanism from the GLP-1 story: ghrelin is produced in the stomach, not the colon, and its suppression is triggered by mechanical stretch and by the arrival of nutrients in the upper gut rather than by SCFA fermentation. The fact that oyster mushrooms affected both GLP-1 via fermentation and ghrelin suppression via satiety signaling suggests these foods are operating on appetite regulation through multiple parallel channels.

Beyond Beta-Glucans: Other Mushroom Compounds and Glucose Metabolism

The incretin pathway via gut fermentation is the best-characterized mechanism for mushroom compounds affecting post-meal glucose hormone release. But mushroom foods contain multiple bioactive classes that affect glucose metabolism through different routes.

Tung and colleagues' 2020 review in Current Pharmaceutical Design catalogued the primary compound classes: beta-glucans and other polysaccharides, lectins, eritadenin, triterpenoids, and sterols.^[6] Each has a distinct mechanism for affecting blood glucose:

Beta-glucans and polysaccharides: the fermentation/SCFA/GLP-1 pathway described above, plus direct viscosity effects that slow glucose absorption from the small intestine.

Lectins: some mushroom lectins have been shown to activate insulin receptors or mimic insulin's downstream signaling directly, a mechanism completely independent of gut fermentation.

Eritadenin (found particularly in shiitake): primarily known for cholesterol-lowering effects but also affects lipid metabolism relevant to insulin signaling.

Triterpenoids (particularly in reishi): demonstrated to inhibit an enzyme called PTP1B, which is a negative regulator of insulin signaling; inhibiting PTP1B effectively amplifies the insulin signal, improving insulin sensitivity without requiring more insulin to be secreted.

Kundakovic and colleagues' 2013 review in Current Topics in Medicinal Chemistry mapped these compound classes to metabolic syndrome criteria, showing that edible mushrooms simultaneously address glucose control (beta-glucans, lectins), lipid profiles (eritadenin, triterpenoids), blood pressure (triterpenoids), and oxidative stress (phenolics), all through different mechanisms acting in parallel.^[7]

Das and colleagues' 2022 review in Pharmaceutics specifically separated the insulin secretagogue mechanisms (compounds that stimulate more insulin to be produced, including via GLP-1) from the insulin sensitizer mechanisms (compounds that make the body respond better to the insulin it already has).^[8] Beta-glucan's GLP-1 pathway is primarily secretagogue. Triterpenoids' PTP1B inhibition is primarily sensitizer. Maitake's SX-fraction and polysaccharide fractions appear to be primarily sensitizers, improving peripheral tissue response to insulin without necessarily increasing insulin production. These are complementary mechanisms, which is part of why whole mushroom consumption affects glucose more broadly than any isolated compound studied on its own.

For a deep look at the specific maitake fractions and the SX-fraction clinical trial data, see maitake and type 2 diabetes: the SX-fraction clinical trials. For the full mushroom species comparison for diabetes, see comparing mushroom species for diabetes management.

The Bottom Line

Mushroom beta-glucans trigger GLP-1 secretion through gut fermentation: polysaccharides resist digestion, reach the colon, feed beneficial bacteria, which produce short-chain fatty acids that activate GPR41/43 receptors on L-cells to release GLP-1. Dicks et al. (2022) demonstrated a 17% postprandial GLP-1 increase from a single oyster mushroom-fortified meal in people with impaired glucose tolerance. Klümpen et al. (2025) showed that baseline gut microbiota composition determines the magnitude of response, with less-balanced microbiomes producing greater GLP-1 boosts. Kleftaki et al. (2022) found king oyster mushroom also produced significantly greater ghrelin suppression than control. The GIP angle remains less directly documented in human studies but is mechanistically plausible via viscosity effects on the proximal gut. Multiple other mushroom compound classes (lectins, triterpenoids, eritadenin) affect glucose metabolism through parallel mechanisms operating alongside the GLP-1 incretin pathway.

Frequently Asked Questions

What are incretin hormones?

Incretin hormones are signaling molecules released by the gut after eating that tell the pancreas to release insulin. GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are the two primary incretins. GLP-1 is produced in the distal small intestine and colon; GIP is produced in the proximal small intestine. Both stimulate insulin secretion and suppress glucagon, working together to keep blood glucose stable after meals. The GLP-1 receptor agonist drugs semaglutide and liraglutide work by activating the GLP-1 receptor directly; mushroom beta-glucans stimulate the body's own GLP-1 production through gut fermentation.

What is the difference between GLP-1 and GIP?

Both are incretin hormones that stimulate insulin secretion after eating, but they are produced by different cell types in different gut locations and have partly different effects. GLP-1, produced by L-cells in the lower gut, additionally suppresses glucagon, slows gastric emptying, and reduces appetite. GIP, produced by K-cells in the upper small intestine, appears to sensitize fat and muscle tissue to insulin and may independently reduce appetite via brain signaling. Tirzepatide (Mounjaro) is more effective than semaglutide partly because it activates both receptors; the gut fermentation pathway activated by mushroom beta-glucans primarily triggers GLP-1 via L-cells in the colon.

What natural foods stimulate incretin hormones?

Foods high in fermentable fiber stimulate GLP-1 via the SCFA fermentation pathway. Gut bacteria ferment these fibers into short-chain fatty acids that activate GPR41 and GPR43 receptors on intestinal L-cells. Oyster mushrooms fortified into a meal raised GLP-1 by 17% in a 2022 RCT by Dicks et al. Other high-beta-glucan sources with similar mechanisms include oats, barley, and other fungi. Fats and glucose in the proximal intestine stimulate GIP from K-cells; both macronutrients and fermentable fibers therefore contribute to the full incretin response after a mixed meal.

Do mushrooms affect GIP as well as GLP-1?

The direct human evidence for mushroom compounds affecting GIP is limited compared to the GLP-1 data. The primary mechanism by which beta-glucans trigger GLP-1 (gut fermentation in the colon) reaches L-cells that produce GLP-1. K-cells that produce GIP are located in the upper small intestine and are primarily stimulated by fats and sugars, not colonic SCFAs. However, beta-glucans also increase food viscosity and slow nutrient release in the proximal gut, which may indirectly modulate the pace of K-cell stimulation. The "dual incretin" parallel to tirzepatide is mechanistically interesting but not yet directly demonstrated in mushroom-specific human studies.

How do beta-glucans trigger incretin release?

Mushroom beta-glucans pass through the stomach and small intestine without being broken down by digestive enzymes, arriving intact in the colon. There, resident gut bacteria (particularly Lactobacillus, Bifidobacterium, and Akkermansia species) ferment them into short-chain fatty acids, primarily acetate, propionate, and butyrate. These fatty acids bind to GPR41 and GPR43 receptors on intestinal L-cells that line the colon. Receptor activation triggers GLP-1 secretion from those L-cells into the bloodstream. The magnitude of the response depends on fermentation capacity, which Klümpen et al. (2025) showed is determined by baseline gut microbiota composition.

What compounds in mushrooms stimulate insulin secretion?

Several mushroom compound classes affect insulin secretion through different mechanisms. Beta-glucans trigger GLP-1 production via gut fermentation, and GLP-1 stimulates insulin secretion from the pancreas. Certain mushroom lectins have been shown to activate insulin receptor signaling directly or to mimic insulin's downstream effects. Triterpenoids (particularly in reishi) inhibit PTP1B, an enzyme that down-regulates insulin signaling, which amplifies the pancreas's sensitivity to glucose. Tung et al. (2020) and Das et al. (2022) both document that these mechanisms are parallel and complementary, which is why whole mushroom consumption tends to show broader glucose effects than any single isolated compound.

Sources & References

1. 1RTHM-00753·Dicks, Lisa et al. (2022). “Fortifying a meal with oyster mushroom powder beneficially affects postprandial glucagon-like peptide-1, non-esterified free fatty acids and hunger sensation in adults with impaired glucose tolerance: a double-blind randomized controlled crossover trial..” European journal of nutrition.Study breakdown →PubMed →↩
2. 2RTHM-02111·Klümpen, Linda et al. (2025). “GLP-1 Responses to a Single Meal Fortified With Oyster Mushroom Powder in Adults With Impaired Glucose Tolerance Depend on the Gut Microbiota Composition Before the Meal..” Molecular nutrition & food research.Study breakdown →PubMed →↩
3. 3RTHM-01577·Ma, Gaoxing et al. (2022). “Health benefits of edible mushroom polysaccharides and associated gut microbiota regulation..” Critical reviews in food science and nutrition.Study breakdown →PubMed →↩
4. 4RTHM-01835·Zhao, Jiahui et al. (2023). “The Interaction between Mushroom Polysaccharides and Gut Microbiota and Their Effect on Human Health: A Review..” Biology.Study breakdown →PubMed →↩
5. 5RTHM-01551·Kleftaki, Stamatia-Angeliki et al. (2022). “Pleurotus eryngii improves postprandial glycaemia, hunger and fullness perception, and enhances ghrelin suppression in people with metabolically unhealthy obesity..” Pharmacological research.Study breakdown →PubMed →↩
6. 6RTHM-00660·Tung, Yu-Tang et al. (2020). “Edible Mushrooms: Novel Medicinal Agents to Combat Metabolic Syndrome and Associated Diseases..” Current pharmaceutical design.Study breakdown →PubMed →↩
7. 7RTHM-00294·Kundaković, Tatjana et al. (2013). “Therapeutic properties of mushrooms in managing adverse effects in the metabolic syndrome..” Current topics in medicinal chemistry.Study breakdown →PubMed →↩
8. 8RTHM-01500·Das, Arpita et al. (2022). “Medicinal Components in Edible Mushrooms on Diabetes Mellitus Treatment..” Pharmaceutics.Study breakdown →PubMed →↩