Enhancing Endogenous GLP-1 Secretion Through Diet: A Nutritional Approach to Managing Type 2 Diabetes and Obesity

Optimising endogenous GLP-1 secretion through nutrition: A supportive dietary approach for improving metabolic health, satiety, and overall wellbeing

Enhancing Endogenous GLP-1 Secretion Through Diet: A Nutritional Approach to Managing Type 2 Diabetes and Obesity Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by intestinal L-cells in response to food intake. It plays a central role in regulating glucose metabolism and appetite, making it a critical target in the prevention and management of type 2 diabetes mellitus (T2DM) and obesity (1). While pharmaceutical GLP-1 receptor agonists are widely used, increasing evidence supports the potential of dietary strategies to naturally enhance GLP-1 secretion (2).

The Role of GLP-1 in Metabolic Health.

GLP-1 enhances insulin secretion in a glucose-dependent manner, inhibits glucagon release, delays gastric emptying, and promotes satiety—all of which contribute to better postprandial glycaemic control and reduced caloric intake (1,3). Due to its short half-life, native GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), yet its effects on appetite and metabolism remain significant when stimulated consistently through diet (4).

Dietary Nutrients That Stimulate.

GLP-1 Nutrient sensing in the gut is mediated by G-protein coupled receptors on L-cells, which respond to macronutrients and trigger GLP-1 secretion (2). Specific dietary components have been shown to enhance endogenous GLP-1 release: Fermentable fibres: Found in oats, legumes, barley, and certain vegetables, fermentable fibres are metabolised by gut microbiota into short-chain fatty acids (SCFAs), particularly butyrate and propionate. These SCFAs activate free fatty acid receptors (FFAR2 and FFAR3), promoting GLP-1 release (2,5).

Monounsaturated and polyunsaturated fats: Healthy fats from sources such as olive oil, nuts, and avocados stimulate GLP-1 secretion via GPR120 and GPR40 receptors (2,6).

Proteins and amino acids: Protein-rich foods, including eggs, dairy, and legumes, enhance GLP-1 secretion through amino acid sensing receptors. Some specific amino acids, such as glutamine and arginine, are particularly effective in stimulating GLP-1 (2,7).

Polyphenols: Plant-derived polyphenols found in berries, green tea, and cocoa may enhance GLP-1 secretion by modulating gut microbiota and increasing L-cell density (8).

Clinical Implications

Diet-induced GLP-1 secretion offers a practical and cost-effective approach to supporting metabolic health. While GLP-1 receptor agonists remain effective pharmacological tools for individuals with established T2DM, dietary modulation provides a valuable complementary strategy, particularly in early intervention or for those at high risk (1,9). Combining a high-fibre, protein-rich diet with healthy fats and polyphenol-rich foods may enhance endogenous GLP-1 production and contribute to improved glycaemic control, satiety, and weight regulation (2,5,7).

Dietary modulation of GLP-1 represents a promising, natural strategy for supporting metabolic health in individuals with or at risk of T2DM and obesity. By integrating specific nutrients and whole foods that stimulate GLP-1 secretion, individuals can improve their insulin response, manage appetite, and support long-term weight and glucose management.

References

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2. Bodnaruc AM, Prud’homme D, Blanchet R, Giroux I. Nutritional modulation of endogenous glucagon-like peptide-1 secretion: a review. Nutr Metab (Lond). 2016;13:92.

3. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409–39.

4. Nauck MA, Vilsbøll T, Gallwitz B, Garber A, Madsbad S. Incretin-based therapies: viewpoints on the way to consensus. Diabetes Care. 2009;32(Suppl 2):S223–31.

5. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein–coupled receptor FFAR2. Diabetes. 2012;61(2):364–71.

6. Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K, et al. Free fatty acids stimulate incretin secretion from mouse enteroendocrine cells by GPR40- and GPR120-dependent mechanisms. Am J Physiol Endocrinol Metab. 2015;308(6):E464–73.

7. Geraedts MC, Troost FJ, Fischer MAJG, Edens L, Saris WH. Direct induction of CCK and GLP-1 release from murine endocrine cells by intact dietary proteins. Mol Nutr Food Res. 2011;55(3):476–84.

8. Psichas A, Sleeth ML, Murphy KG, Brooks L, Bewick GA, Hanyaloglu AC, et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes (Lond). 2015;39(3):424–9.

9. Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018;391(10120):541–51.