In this interview Professor Rémy Burcelin, Head of Research Inserm, tells his story about the search for sensitive insulin, glucagon and GLP-1 markers.
Prof. Rémy Burcelin and his team aims at identifying the intestinal risk factors which control glycemia, dyslipidemia and heart failure. They identified the first molecular mechanisms in which the gut hormone incretin GLP-1 controls energy metabolism through the triggering of a gut-brain to the periphery axis. Recent discoveries have shown that a fat-enriched diet can lead to accumulation of bacterial determinants in the blood which are responsible for the triggering of metabolic inflammation leading to type 2 diabetes and obesity.
The quest for sensitive insulin, glucagon and GLP-1 markers
“I arrived in Switzerland in 1995 to work in a biotech company together with Prof. Bernard Thorens. The aim of the project was to show how GLP-1, released by the intestine, could trigger other organs including the pancreas. The difficulty was to know the released dose and the physiological effects.
Since GLP-1 is a rapidly degraded hormone, effective distal organ action must depend on other mechanisms than the purely hormonal one. This other mechanism was the activation of a GLP-1 receptor in the portal vein that transmitted a nerve signal to the brain which redistributed this signal to the beta cells to induce the secretion of insulin, as well as to the alpha cells to block the secretion of Glucagon.
It was necessary to show the mode of action of enteric GLP-1 on the portal vein and one criterion for validating this was insulin secretion. To demonstrate this we used mice, genetically modified for the GLP-1 receptor. Since the portal vein in mice is extremely small it was necessary to work with a maximum of 10 to 50 microliters of plasma to effectively quantify the insulin secreted. So, we had to find a suitable kit since RIA, the radioimmunology conventionally used at the time, required at least 100 microliters of plasma.
“We found that the sensitivity of the Mercodia kits were very satisfactory”
It was in a booth at a EASD congress that I met the Mercodia team. They offered a kit for insulin measurement by ELISA, and we found that the sensitivity of the Mercodia kit (Insulin ELISA) was very satisfactory. Suddenly we were able to quantify insulin in the samples from our physiological tests.
The next challenge was to show that this endocrine gut/brain/pancreas axis, validated for insulin in mice, was also true for glucagon. The Mercodia team had an extremely functional kit (Glucagon ELISA) for this purpose, and we found that it was very sensitive, reliable, and reproducible. We were pleased to now also demonstrate that GLP-1 controlled the concentration of glucagon in a gut/brain, brain/pancreas endocrine axis.
At the time we were also in search of an GLP-1 ELISA kit, but few suppliers sold concrete, usable kits, to allow us to have reproducible results. It was necessary to measure GLP-1 once secreted, and not only the GLP-1 administered by infusion or at the time of injection in animals. The Total GLP-1 ELISA from Mercodia turned out to be very satisfying. It allowed us to assay the active form, in particular N terminal, and the C terminal form which reflected, the overall forms, active and inactive.
So, all in all, we now had our panoply of insulin/glucagon/GLP-1 ELISA kits, which allowed us to conduct our physiological experiments in small animals, i.e., mice.”
Thank you, Prof. Burcelin, for sharing your story!
Based on an interview with Prof. Burcelin by Myriam Kacimi (Area Manager France, Mercodia).