GLP-1, a Future Diagnostic Biomarker of Intestinal Infarction?

Science

Mesenteric infarction – an acute emergency – remains a little-known condition that is often underestimated because it is so difficult to diagnose. While seeking to gain a better understanding of certain biological regulation pathways, scientists discovered that GLP-1 – until now known as a mediator regulating blood glucose levels – is rapidly and intensively produced in a model close to that of mesenteric infarction. Its potential as a new diagnostic tool now needs to be confirmed.

The non-specificity of symptoms associated with intestinal infarction explains why treatment is sometimes delayed. The availability of a diagnostic biomarker would make it possible to intervene quicker, thereby saving many lives.

GLP-1 (glucagon-like peptide-1) is a peptide secreted by the endocrine cells of the intestine after food is ingested: its role in terms of regulating glucose metabolism has been extensively described. However, although the underlying mechanism for this is not fully understood, it has also been observed that GLP-1 levels increase when certain bacterial components – lipopolysaccharides (LPS) – manage to cross the gut barrier. In Dijon, a team* of researchers focused on this phenomenon. It demonstrated a direct link between increased exposure to LPS and increased GLP-1 concentrations in the event of damage to the gut. The team’s work could result in a hitherto unforeseen application, since the intestinal mucosa is very rapidly damaged during a mesenteric infarction. It then seems to be incapable of fulfilling its barrier function and is easily breached by the LPS produced by local bacterial flora, triggering the increased secretion of GLP-1.

Towards a reduction in mortality related to the disease

“The issue is more important than we may realize,” emphasizes Jacques Grober, who was involved in the research. “Mesenteric infarction is a little-known condition because it is less common than infarctions affecting the heart, with just 0.1% of hospital admissions thought to be related to the problem. But the figures are alarming when you consider that the death rate related to this emergency is 60 to 80% within the first 24 hours.” This is due to the delay in its diagnosis: “Intestinal ischemia primarily manifests as severe but relatively non-specific abdominal pain and there is currently no method of diagnosing it at an early stage.” Detecting the condition more quickly would enable earlier treatment and offer patients a better prognosis. And GLP-1 may be the solution.

The scientists first of all demonstrated that, in animals, large quantities of GLP-1 were rapidly released into the blood circulation following damage to the gut lining, then in the event of intestinal ischemia when the lack of oxygen quickly causes lesions. They then observed that this phenomenon was triggered by the LPS produced by certain gut bacteria, which became capable of penetrating the epithelium in the event of damage to it. Finally, these observations were confirmed in humans, via two series of studies. In one, small concentrations of LPS were injected into the blood of healthy volunteers, after the other had demonstrated an increase in GLP-1 levels in transient intestinal ischemia scenarios.

These results represent a first step towards the use of GLP-1 for diagnostic purposes. Prior to this, two main questions need to be answered. The first – very pragmatic – question is to determine the normal values for this biomarker. “Since it is related to glucose metabolism, it will be necessary to perform a whole series of analyses to assess the threshold GLP-1 values to be used to diagnose an infarction, depending on whether the patient is fasting or otherwise, or whether or not he or she is diabetic, for example.” The second question is more fundamental, but just as important: why is a mediator of glucose homeostasis influenced by an infectious component? On this point, Grober puts forward a hypothesis, related to the emerging role of GLP-1 in inflammatory mechanisms, recently described in the literature. It seems that some of the secrets of this biomarker have yet to be revealed...

Note

* Inserm unit 1231/Université de Bourgogne Franche-Comté/Agro Sup Dijon, Lipid transfer proteins and lipoprotein metabolism team, Lipids - Nutrition - Cancer (LNC), Dijon

Source

Lebrun LJ et al. Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion. Cell Reports 21, 1160–1168, October 31, 2017. https://doi.org/10.1016/j.celrep.2017.10.008

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