Glicentin

Glicentin and intestinal physiology

First, several studies in rat model have highlighted the trophic role of glicentin on intestinal mucosa. An increase of several parameters of mucosal growth, including weight, protein and DNA content, alkaline phosphatase and ornithine decarboxylase activities have been reported in the jejunum after glicentin subcutaneous injection. In vitro studies confirmed the proliferative action of glicentin on epithelial cell line IEC-6. In addition, a decrease of crypt fission in the ileum after glicentin administration was observed. It pinpoints the potential role of glicentin in intestinal mucosa remodeling. In addition to its trophic effect on intestinal mucosa, glicentin may also act as a barrier-sustaining agent. The effect of recombinant human glicentin on bacterial internalization by confluent INT407 enterocytes cell lines using Salmonella enteritidis, Escherichia coli and Enterococcus faecalis was determined. A lower bacterial internalization through the glicentin-treated enterocytes was observed compared to the non-treated cells. Glicentin can also stimulate the digestive tract smooth muscle contraction, an effect which may involve GLP-1 receptor. Using human gastric biopsies, it has been revealed that glicentin mRNA expression was associated with the existence of histological intestinal metaplasia and positively correlated with Helicobacter infection. Given its biological function, glicentin also shows potential role in the context of digestive oncology.

Clinical significance of Glicentin

Glicentin has a role in glucose metabolism and intestinal physiology, and may be useful for diagnosing and treating metabolic disorders, and may be useful in the following ways:

• Diagnosing noninvasive conditions

 it was recently demonstrated that postprandial response of glicentin, but not of any other proglucagon peptide, is impaired in early stages of NAFLD, which suggests that glicentin may be useful for the noninvasive diagnosis of the disease.

• Predicting metabolic outcomes

Glicentin, due to its longer half-life, may be able to serve as a more reliable marker of L-cell function compared to GLP-1. In that case, its diagnostic or prognostic value should be further tested in obesity and its comorbidities. For example, its levels after bariatric surgery could be used to identify patients who will eventually have a more robust response vs those that will need more intense postoperative care to achieve sufficient weight loss or could predict other metabolic outcomes in the long term.