Perspectives in GLP-1 Research: New Targets, New Receptors.
The incretin hormone glucagon-like peptide-1 (GLP-1) binds to and activates its G-protein-coupled-receptor GLP-1R to reduce glycaemia through the stimulation of insulin and suppression of pancreatic glucagon secretion. Recently, GLP-1 effects unrelated to glucose homeostasis have been discovered in myocardium, bone, adipose tissue, and other target organs, which appear to be mainly mediated by GLP-1R-independent pathways. Here, we summarize knowledge on GLP-1R agonists (GLP-1RAs) as they relate to the improvement of glucose control, and focus on the most recently described effects, discussing the preclinical evidence of the involvement of alternative receptors and signalling mechanisms. It is now evident that the universe of GLP-1RAs is expanding further from the initial incretin effect, opening new unforeseen avenues for research and clinical applications.
Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy. Electronic address: giulia.cantini@unifi.it.
Giulia
G
Cantini
Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy; Diabetes Agency, Careggi Hospital, Florence, Italy.
Edoardo
E
Mannucci
Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy. Electronic address: michaela.luconi@unifi.it.
Michaela
M
Luconi
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D052216:Glucagon-Like Peptide 1; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
GLP-1 receptor agonists; cardioprotection; glucagon-like peptide-1; incretins