Unlocking the multifaceted roles of GLP-1: Physiological functions and therapeutic potential

Abstract

Glucagon (GCG) like peptide 1 (GLP-1) has emerged as a powerful player in regulating metabolism and a promising therapeutic target for various chronic diseases. This review delves into the physiological roles of GLP-1, exploring its impact on glucose homeostasis, insulin secretion, and satiety. We examine the compelling evidence supporting GLP-1 receptor agonists (GLP-1RAs) in managing type 2 diabetes (T2D), obesity, and other diseases. The intricate molecular mechanisms underlying GLP-1RAs are explored, including their interactions with pathways like extracellular signal-regulated kinase 1/2 (ERK1/2), activated protein kinase (AMPK), cyclic adenine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Expanding our understanding, the review investigates the potential role of GLP-1 in cancers. Also, microribonucleic acid (RNA) (miRNAs), critical regulators of gene expression, are introduced as potential modulators of GLP-1 signaling. We delve into the link between miRNAs and T2D obesity and explore specific miRNA examples influencing GLP-1R function. Finally, the review explores the rationale for seeking alternatives to GLP-1RAs and highlights natural products with promising GLP-1 modulatory effects.

Keywords: Cancer; Diabetes; GLP-1; GLP-1RAs; Natural products; Obesity; miRNAs.

Fig. 1

Pleiotropic effects of GLP-1 . [CNS: central nervous system; CVS: Cardiovascular system; GIT: Gastrointestinal tract; GLP-1R: Glucagon like peptide-1 receptor; VLDL: very low-density lipoprotein].

Fig. 2

The complex interplay between GLP-1RAs and several cellular signaling pathways. [AMPK: activated protein kinase; cAMP: cyclic adenine monophosphate; ERK 1/2: extracellular signal-regulated kinase 1/2; GLP-1R: Glucagon like peptide-1 receptor; MAPK: Mitogen-activated protein kinase; PKC: protein kinase C].

Fig. 3

Intracellular signaling through Gαs mediated by GLP-1R. [GLP-1R: Glucagon like peptide-1 receptor; ATP: adenosine triphosphate; cAMP: cyclic adenine monophosphate; Epac: exchange protein directly activated by cAMP; PKA: protein kinase A; ERK1/2: Extracellular signal-regulated kinase 1/2; AKT: protein kinase B; mTOR: Mammalian target of rapamycin; CREB: cAMP-response element binding protein].

Fig. 4

GLP-1R: The Key to Unlocking Weight Loss? Exploring Potential Mechanisms .

Fig. 5

The interplay between GLP-1RAs and different types of cancer.

Fig. 6

A Schematic Representation of microRNA Biogenesis.

Fig. 7

Unveiling the hidden regulators: miRNAs and GLP-1R signaling.

Fig. 8

Exploring natural products that modulate GLP-1.