Maintaining normal glucose homeostasis is essential for a cell's survival and function. A cell uses various mechanisms for regulating optimal glucose levels. Glucagon-like peptide-1 (GLP-1) is one of the incretins that regulate glucose metabolism. GLP-1 is a peptide hormone secreted by L cells in the ileum and colon. GLP-1 promotes insulin secretion from pancreatic β cells via activation of cAMP-mediated protein kinase A (PKA). There are reports on PKA-independent activation of GLP-1 via PLC/PKC pathway1. Besides promoting insulin secretion, GLP-1 is involved in insulin synthesis, β cell proliferation and apoptosis2. GLP-1 plays a pivotal role in regulating blood glucose levels and influencing overall metabolic processes (Fig. 1).
Fig. 1 Role of GLP-1 in overall metabolism2
Berberine is known for its hypoglycaemic effects. There are various mechanisms through which berberine interacts with GLP-1 to regulate blood glucose levels. A study reported that berberine facilitates GLP-1 production by activating the β-catenin/TCF4 signalling pathway and via miR-106b downregulation3. Another study reported that the bitter taste of berberine causes the activation of bitter taste receptors (TAS2Rs), which further activates the downstream signalling pathway, leading to enhanced GLP-1 secretion4. Various in vitro and clinical studies support the idea that berberine maintains blood glucose levels by promoting GLP-1 secretion. A study observed that the number of GLP-1 positive L cells increased after berberine treatment. Additionally, the expression of genes involved in GLP-1 biosynthesis was increased (proglucagon and prohormone convertase 3)5. A similar study reported that berberine treatment significantly elevates the number of GLP-1 positive L cells in mice. Additionally, the mRNA expression of proglucagon exhibited 3-fold upregulation in the berberine treatment group6.
Overall, it can be concluded that berberine effectively enhances GLP-1 secretion, stimulating insulin secretion and ultimately maintaining normal glucose homeostasis.
References
- Shigeto, M.; Cha, C. Y.; Rorsman, P.; Kaku, K. A Role of PLC/PKC-Dependent Pathway in GLP-1-Stimulated Insulin Secretion. Journal of Molecular Medicine. Springer Verlag April 1, 2017, pp 361–368. https://doi.org/10.1007/s00109-017-1508-6.
- Müller, T. D.; Finan, B.; Bloom, S. R.; D’Alessio, D.; Drucker, D. J.; Flatt, P. R.; Fritsche, A.; Gribble, F.; Grill, H. J.; Habener, J. F.; Holst, J. J.; Langhans, W.; Meier, J. J.; Nauck, M. A.; Perez-Tilve, D.; Pocai, A.; Reimann, F.; Sandoval, D. A.; Schwartz, T. W.; Seeley, R. J.; Stemmer, K.; Tang-Christensen, M.; Woods, S. C.; DiMarchi, R. D.; Tschöp, M. H. Glucagon-like Peptide 1 (GLP-1). Molecular Metabolism. Elsevier GmbH December 1, 2019, pp 72–130. https://doi.org/10.1016/j.molmet.2019.09.010.
- Wang, J.; Wei, L. R.; Liu, Y. L.; Ding, C. Z.; Guo, F.; Qin, Q.; Huang, F. J.; Xin, Y.; Ma, S. N.; Zhai, Q. R.; Wang, S. J.; Qin, G. J. Berberine Activates the β-Catenin/TCF4 Signaling Pathway by down-Regulating MiR-106b to Promote GLP-1 Production by Intestinal L Cells. Eur J Pharmacol 2021, 911. https://doi.org/10.1016/j.ejphar.2021.174482.
- Araj-Khodaei, M.; Ayati, M. H.; Azizi Zeinalhajlou, A.; Novinbahador, T.; Yousefi, M.; Shiri, M.; Mahmoodpoor, A.; Shamekh, A.; Namazi, N.; Sanaie, S. Berberine-Induced Glucagon-like Peptide-1 and Its Mechanism for Controlling Type 2 Diabetes Mellitus: A Comprehensive Pathway Review. Archives of Physiology and Biochemistry. Taylor and Francis Ltd. 2023. https://doi.org/10.1080/13813455.2023.2258559.
- Yu, Y.; Liu, L.; Wang, X.; Liu, X.; Liu, X.; Xie, L.; Wang, G. Modulation of Glucagon-like Peptide-1 Release by Berberine: In Vivo and in Vitro Studies. Biochem Pharmacol 2010, 79 (7), 1000–1006. https://doi.org/10.1016/j.bcp.2009.11.017.
- Xu, J. H.; Liu, X. Z.; Pan, W.; Zou, D. J. Berberine Protects against Diet-Induced Obesity through Regulating Metabolic Endotoxemia and Gut Hormone Levels. Mol Med Rep 2017, 15 (5), 2765–2787. https://doi.org/10.3892/mmr.2017.6321.
