Insights on glicentin, a promising peptide of the proglucagon family

Abstract

Glicentin is a proglucagon-derived peptide mainly produced in the L-intestinal cells. While the roles of other members of the proglucagon family including glucagon-like peptide 1, glucagon-like peptide 2 and oxyntomodulin has been well studied, the functions and variation of glicentin in human are not fully understood. Experimental and clinical studies have highlighted its role in both intestinal physiology and glucose metabolism, pointing to its potential interest in a wide range of pathological states including gastrointestinal and metabolic disorders. Due to its structure presenting many similarities with the other proglucagon-derived peptides, its measurement is technically challenging. The recent commercialization of specific detection methods has offered new opportunities to go further in the understanding of glicentin physiology. Here we summarize the current knowledge on glicentin biogenesis and physiological roles. In the limelight of clinical studies investigating glicentin variation in human, we discuss future directions for potential applications in clinical practice.

Keywords: enteroendocrine cells; glicentin; glucagon-like peptide; oxyntomodulin; proglucagon.

Figure 1

Processing of the proglucagon gene into proglucagon-derived peptides (modified from Baggio et al. (4), Holst et al. (5), Bataille et al. (6, 7), Whiting et al. (8)) and DeFronzo et al. (47)). (1) The proglucagon gene is located on the chromosome 2 and is composed of 6 exons and 5 introns. (2) The gene transcription leads to a messenger RNA. (3) The messenger RNA (mRNA) is translated into the proglucagon, a 178 amino-acid precursor protein. (4) Posttranslational processing in the alpha pancreatic cells involves mainly the proconvertase 2 (PC2) and leads to the glicentin related pancreatic polypeptide (GRPP), the glucagon, the intervening peptide-1 (IP-1) and the major proglucagon fragment (MPF). (5) An alternative pathway involving proconvertase 1 and 3 (PC1/3) can lead to glucagon like peptide 1 (GLP-1) formation in the pancreas. (6) In the enteroendocrine L-cells and in the central nervous system, post-translational processing of proglucagon is mediated by proconvertases 1 and 3 and liberates the glicentin, the oxyntomodulin, the glucagon like peptide 1, the Intervening Peptide-2 (IP-2) and the glucagon like peptide 2 (GLP-2). DNA - deoxyribonucleic acid.