Insights on glicentin, a promising peptide of the proglucagon family.

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.

The forgotten members of the glucagon family.

From proglucagon, at least six final biologically active peptides are produced by tissue-specific post-translational processing. While glucagon and GLP-1 are the subject of permanent studies, the four others are usually left in the shadow, in spite of their large biological interest. The present review is devoted to oxyntomodulin and miniglucagon, not forgetting glicentin, although much less is known about it. Oxyntomodulin (OXM) and glicentin are regulators of gastric acid and hydromineral intestinal secretions. OXM is also deeply involved in the control of food intake and energy expenditure, properties that make this peptide a credible treatment of obesity if the question of administration is solved, as for any peptide. Miniglucagon, the C-terminal undecapeptide of glucagon which results from a secondary processing of original nature, displays properties antagonistic to that of the mother-hormone glucagon: (a) it inhibits glucose-, glucagon- and GLP-1-stimulated insulin release at sub-picomolar concentrations, (b) it reduces the in vivo insulin response to glucose with no change in glycemia, (c) it displays insulin-like properties at the cellular level using only a part of the pathway used by insulin, making it a good basis for developing a pharmacological workaround of insulin resistance.