Molecular Research on Proglucagon-Derived Peptides
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".
Deadline for manuscript submissions: 31 October 2025 | Viewed by 20
Special Issue Editor
Special Issue Information
Dear Colleagues,
The structurally related proglucagon-derived peptides (PGDPs), including glucagon-like peptides (GLPs), oxyntomodulin, glicentin, and glucagon, are encoded by a single mammalian proglucagon gene (gcg). Several homeodomain (HD) proteins are able to activate the expression of the gcg gene by interacting with its promoter, while gcg expression is also controlled by protein kinase A and Epac signaling in response to cAMP elevation, as well as cell type, specifically by the Wnt signaling pathway. The resulting proglucagon is expressed in pancreatic islets, the intestine, and the central nervous system (CNS), where prohormone convertase (PC) enzymes and the post-translational processing of proglucagon liberate peptide hormones in a tissue-specific manner. PC2 is essential for the generation of pancreatic glucagon in islet α-cells, whereas PC1/3 is essential for the generation of glucagon-like peptides (GLPs) in enteroendocrine L-cells, and neurons located in the solitary nucleus of the medulla oblongata also utilize PC1/3 to generate PGDPs in the CNS. However, this tissue specificity is not absolute, and under certain circumstances, islet α-cells produce GLP-1, oxyntomodulin, and glicentin, whereas enteroendocrine L-cells may produce glucagon
Glucagon is secreted from islet α-cells in response to alterations in blood glucose and GLPs in the intestine in response to nutrient ingestion. PGDPs exert their effects through distinct G-protein-coupled receptors (GPCRs), and act on various tissues including the intestine, pancreatic islets, and brain. PGDPs have pleiotropic biological properties, controlling cell proliferation, energy homeostasis, and cytoprotection. Moreover, stable analogs (glucagon, GLP-1, and GLP-2), inhibitors of degradation (GLP-1), and antagonists (glucagon) have been developed for the treatment of common diseases such as obesity, diabetes, and neurodegenerative and cardiovascular disease.
In this Special Issue of IJMS, we will focus on molecular mechanisms underlying the biogenesis, activation, secretion, and actions of proglucagon-derived peptides in human health and diseases.
Dr. Camilla Krizhanovskii
Guest Editor
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Keywords
- proglucagon
- peptide hormones
- post-translational processing
- prohormone convertase
- G-protein-coupled receptors
- tissue specificity
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