Glucagon like peptide-1 (GLP-1) is a powerful gut hormone that regulates appetite, satiety, and blood sugar levels. While GLP-1 medications like Ozempic are gaining popularity, you can also support natural GLP-1 production through your diet. This article explains how nutrients, especially resistant starch and prebiotic fibers, stimulate GLP-1 secretion in the gut, promoting better metabolic health, improved insulin response, and reduced hunger. Learn how foods like oats, beans, and just-ripe bananas can help, and get practical tips to activate GLP-1 naturally.
Glucagon-like peptide-1 (GLP-1) is a hormone produced and secreted by cells lining the gastrointestinal (GI) tract, particularly in the large intestine. GLP-1 plays a crucial role in regulating several physiological and metabolic functions, including appetite, satiety, glucose and insulin balance, GI motility, liver fat metabolism, and even bone remodeling (1). Over the past several years GLP-1 receptor agonists have been developed as medications for managing diabetes, cardiovascular disease, and obesity. These drugs mimic GLP-1 to promote weight loss and improve metabolic health.
GLP1s Roles in the Body
GLP-1 is an incretin, a hormone that promotes insulin release from the pancreas in response to elevated blood glucose after eating. This “incretin effect” only occurs when foods containing glucose (e.g., starches and carbohydrates) enter the GI tract and does not happen with intravenous glucose administration.
Beyond stimulating insulin, GLP-1 improves the function and viability of the pancreatic beta cells, which are the cells responsible for making and releasing insulin. It also inhibits glucagon secretion from the alpha-cells of the pancreas, which is an opposing hormone to insulin. Insulin brings glucose into the skeletal muscle and adipose tissue for metabolism when glucose levels are elevated. Glucagon is released when blood glucose levels are low to stimulate the formation of new glucose in the liver and kidneys. In individuals with obesity and diabetes, the incretin effect is diminished, contributing to poor glucose tolerance.
Although skeletal muscle and the liver do not contain GLP-1 receptors, GLP-1 still influences these tissues indirectly via insulin and glucagon. (1) GLP-1 receptors are present in other organs including pancreas, heart, brain, lungs, adipose, kidneys, GI tract, adrenal glands, spleen, and eyes. The brain, after the pancreas, contains the highest density of GLP-1 receptors helping explain GLP-1s impact on appetite regulation and satiety (see Figure 1).
Saraiva & Sposito 2014 Cardio Diab
How GLP-1 Receptor Agonists Work
Native GLP-1 has a short half-life of just 1-2 minutes because it is rapidly broken down in the blood by the enzyme dipeptidyl peptidase 4 (DPP-4). Once GLP-1 is cleaved by DPP-4 it becomes inactive and cannot bind to its receptors.
GLP-1 receptor agonists, however, have a very similar composition to GLP1 but are designed to resist breakdown by DPP-4 (Figure 2). The receptor agonists can bind to the GLP-1 receptors to mimic natural GLP-1 and stay in the blood much longer. For example, semaglutide (Ozempic) has a half-life of ~7 days.
Due to this extended activity, side effects can last several days, which is why these medications are typically started at low doses and gradually titrated to the desired level. Interestingly, normal physiological levels of GLP-1 do not significantly stimulate metabolism, but prolonged elevation from receptor agonists can have a meaningful effect.
Nutrients that Stimulate GLP-1 Secretion (also known as secretagogues)
GLP-1 is produced in L cells which are abundant in the lining of the large intestine (Figure 3). Within the L cells the proglucagon gene is transcribed into proglucagon, which is cleaved by enzymes to form GLP-1.
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Certain nutrients bind to receptors on the L cells, including G-protein, bile acid, and calcium-sensing receptors to stimulate the secretion of GLP-1. These nutrient-based secretagogues include:
· Dietary lipids, especially triacylglycerol which is the primary fat found in foods
· Dietary carbohydrates, particularly those yielding glucose
· Short chain fatty acids (SCFAs) produced from fiber fermentation by gut microbes
The high density of L-cells in the large intestine makes it a prime target for SCFA-mediated GLP-1 secretion. One of the most potent SCFAs is butyrate, which is generated by the microbial fermentation of prebiotic fibers. Butyrate binds to the L-cell receptors that triggers GLP-1 release.
The Role of Prebiotic Fibers and Resistant Starch
Prebiotic fibers are a natural way to stimulate GLP-1 release from the gut. These fibers are found in a variety of fruits, vegetables, whole grains, and legumes and beans.
One key prebiotic fiber, resistant starch, is found in starchy foods like potatoes, oats, beans, and just-ripe bananas. Because resistant starch resists digestion in the small intestine, it reaches the large intestine intact and is fermented by the beneficial gut microbes. This process ultimately produces butyrate and releases GLP-1.
Although GLP-1s activity is short lived, it contributes to satiety and blood sugar regulation. A feedback loop between GLP-1 and the afferent nerve fibers in the gut slows the movement of the GI tract thus slowing digestion. Slowing gut motility contributes to feelings of fullness and satiety to regulate food intake.
3 Practical Tips to Naturally Stimulate GLP-1
1. Focus on prebiotic fibers, especially resistant starch, which are found in just-ripe bananas, potatoes, oats, beans, legumes, and peas. Include fiber-rich foods at each meal.
2. Consume probiotic-rich foods daily, like Greek yogurt, kefir, kombucha, and kimchi each day.
3. Consider a prebiotic fiber supplement like Renutrin. Renutrin contains resistant starch to fuel beneficial gut bacteria. While supplements should not replace whole-food sources of dietary fiber, they can complement the diet and support gut health.
References:
( (1) Nauck MA et al. 2021 Diabetes Obes Metab