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Oxyntomodulin

Analyte: Oxyntomodulin

Specimen Type: Plasma with the appropriate preservatice (see Additives & Collection Inst.)

Optimum Volume: 0.5 mL

Stability:

2-8°C -20°C -70°C
4 days 21 days 22 months

Reporting units: pg/mL

Method: RIA

Biological or Clinical Significance:

The structure of oxyntomodulin was elucidated in 1981.  It is a 37 amino acid peptide that contains the 29 amino acid sequence of glucagon followed by an eight amino acid carboxyterminal extension.

Many of the functions of oxyntomodulin have been worked out in rodents.  It inhibits postprandial gastric acid secretion.  In addition, oxyntomodulin displays weak affinity for the glucagon receptor and may mimic glucagon actions in the liver and pancreas.  Thus, oxyntomodulin mimics the effects of GLP-1 and GLP-2.

Oxyntomodulin has also been shown to inhibit food intake.  The anorectic actions of oxyntomodulin are blocked by the GLP-1 receptor antagonist Exendin (9-39).

Repeated IP administration of oxyntomodulin over seven days caused a reduction in the rate of body weight gain and adiposity in rats.  Delivery of oxyntomodulin into the GI tract of overweight BALB/C mice through a bacterial plasmid delivery system was associated with reduced food intake and weight gain, despite no changes in plasma levels.

Studies of oxyntomodulin action in mice have demonstrated that although the hormone can activates both glucagon and GLP-1 receptors, its anorectic actions require only the GLP-1 receptor.  Furthermore, Exendin-4, but not oxyntomodulin, regulates energy expenditure in mice.  Hence, it appears to be a weak agonist at the GLP-1 receptor, when used in pharmacological concentrations.  Oxyntomodulin also mimics many of the actions of GLP-1 on the islet beta cell, including stimulation of glucose-dependent insulin secretion and activation of cell survival pathways leading to reduced beta cell apoptosis.

In humans, a 90 min oxyntomodulin infusion decreased the sensation of hunger and inhibited meal-related energy intake and decreased cumulative 12 h energy intake, but not 24 h energy intake.  Interestingly, infusion of the hormone also decreased circulating levels of ghrelin in the fasting and postprandial state.  The effects of oxyntomodulin on food intake and energy expenditure in overweight and obese subjects have been studied.  When oxyntomodulin was self-administered three times a day before each meal for 4 d, energy intake was reduced by ~17%, and body weight was reduced by 0.5 kg.

The precise mechanisms utilized by oxyntomodulin for transduction of various biological actions remain unclear.  Its importance as a biologically active peptide would be greatly strengthened by the identification of a separate oxyntomodulin receptor, or by studies employing specific oxyntomodulin antagonists or immunoneutralizing antisera that blocked actions of oxyntomodulin but not glucagon or GLP-1.

Because of the 29 amino acid sequence homology with glucagon, radioimmunoassays using antisera that are not specific for both the C-and N-terminus of oxyntomodulin will also cross-react with glucagon, and possibly glicentin.  Hence much of the earlier literature assessing circulating oxyntomodulin using non-specific assays may not be 100% accurate.

Principle of Test Method:

The Oxyntomodulin assay is a competitive radioimmunoassay.

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