Oxyntomodulin and Glicentin: Novel Biomarkers of Gastrointestinal and Metabolic Disorders

Oxyntomodulin and Glicentin: Novel Biomarkers of Gastrointestinal and Metabolic Disorders

(for research use only)

Introduction

♦ Oxyntomodulin and Glicentin are secreted from enteroendocrine L-cells and  neuronal cells of brain along with glucagon-like peptide-1,  glucagon-like peptide-2 and peptide YY.

♦ Oxyntomodulin, which contains the glucagon sequence with a carboxyterminal extension, is a dual agonist of glucagon and GLP-1 receptors

♦ Glicentin, which contains the sequence of oxyntomodulin (and thus also of glucagon) with an N-terminal extension, and its receptor remains unknown

♦ Similar to GLP-1, oxyntomodulin and  glicentin has an insulinotropic action and exerts an incretin-like effect.

♦ OXM and glicentin inhibits food intake and stimulates energy expenditure in rodents and in human subjects.

♦ GLP-1 has a very short half-life of only 1 to 2 minutes, whereas oxyntomodulin has a circulating half-life of 12 minutes, and the predicted half-life of glicentin is around 30 to 35 minutes

Clinical Studies

Early-stage biomarker for nonalcoholic fatty liver disease (NAFLD)

♦ Circulating levels of GLP-1, GLP-2, glicentin, oxyntomodulin, glucagon, MPGF were measured in individuals with early stage NAFLD , biopsy proven NAFLD and nonalcoholic steatohepatitis [NASH]

♦ Patients in early stages of NAFLD demonstrated higher fasting MPGF and lower incremental increase of glicentin during oral glucose tolerance test than controls.

Best predictors of weight loss after gastric bypass surgery

♦ Postprandial responses of glicentin, oxyntomodulin, GLP-1, peptide YY (PYY), and ghrelin were measured before and 6 months after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG).

♦ Enhanced responses of oxyntomodulin and glicentin predicted a greater weight loss  and were associated with a larger decrease in energy density. No association between GLP-1 and weight loss

Ansh Labs’ Oxyntomodulin  ELISA (AL-139) and Ansh Labs’ Glicentin ELISA (AL-185)

References

• Pocai A. Action and therapeutic potential of oxyntomodulin. Mol Metab. 201314;3(3):241-51.
• Raffort et al, Insights on glicentin, a promising peptide of the proglucagon family. Biochem Med (Zagreb). 2017 Jun 15;27(2):308-324.
• Perakakis N, Mantzoros CS. The Role of Glicentin and Oxyntomodulin in Human Metabolism: New Evidence and New Directions. J Clin Endocrinol Metab. 2020 Aug 1;105(8):dgaa329.
• Polyzoset al, . Targeted Analysis of Three Hormonal Systems Identifies Molecules Associated with the Presence and Severity of NAFLD. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e390–400.
• Perakakis et al, Circulating levels of gastrointestinal hormones in response to the most common types of bariatric surgery and predictive value for weight loss over one year: Evidence from two independent trials. Metabolism. 2019 Dec;101:153997.
• Kim et al, Effect of liraglutide vs. placebo treatment on circulating proglucagon-derived peptides that mediate improvements in body weight, insulin secretion and action: a randomized controlled trial. Diabetes Obes Metab. 2020 Nov 2. doi: 10.1111/dom.14242.