GLP-1, GIP and Glucagon: the Three Hormones Behind the Agonists Studied in Research
What incretins are, what glucagon does, and why research is interested in molecules that activate one, two or three of these receptors.
Contents
The names GLP-1, GIP and glucagon appear in many recent publications on metabolism. They are three peptide hormones naturally produced by the body, each acting on its own receptor. Understanding their role helps when reading the literature on so-called single, dual or triple agonist molecules.
Incretins: GLP-1 and GIP
The term incretin refers to hormones secreted by the gut after a meal, which amplify insulin release by the pancreas according to the glucose present.
- GLP-1 (*glucagon-like peptide-1*) is produced by the L cells of the intestine. It acts on the GLP-1R receptor, found notably in the pancreas, the stomach and certain brain regions.
- GIP (*glucose-dependent insulinotropic polypeptide*) is produced by the K cells of the duodenum. It acts on the GIPR receptor, found in the pancreas and also in adipose tissue.
Both hormones are very short-lived in the body: they are rapidly broken down by an enzyme, DPP-4.
Glucagon: the hormone working the other way
Glucagon is produced by the alpha cells of the pancreas. It acts on the GCGR receptor, highly present in the liver, and its classic role is the opposite of insulin's: mobilizing energy reserves. The literature also attributes effects on energy expenditure to it, which explains research interest in this receptor.
More stable analogues
The natural hormones disappear within minutes. To study them or draw inspiration from them, peptide chemistry has developed modified analogues: amino-acid substitutions, addition of a lipid chain to bind albumin, and so on. These modifications extend their duration of action and allow one or several receptors to be targeted.
Single, dual or triple agonist
- Single agonist: the molecule activates one receptor (GLP-1R, for example).
- Dual agonist: it activates two receptors (GLP-1R and GIPR, for example).
- Triple agonist: it activates GLP-1R, GIPR and GCGR. This is the family of RT-3, whose literature is summarized in our article RT-3: summary of the literature.
The idea explored by research is to combine complementary mechanisms. The balance between the three activities, specific to each molecule, is one of the most studied topics.
And amylin?
Another pancreatic hormone, amylin, is the subject of parallel work with its own analogues, such as cagrilintide (see Cagrilintide and amylin).
Key takeaway
GLP-1, GIP and glucagon are three distinct hormones with three distinct receptors. The molecules studied in research are defined by the receptors they activate and by the balance between these activities. Published results concern specific study conditions and do not transfer to other uses.
To learn more
Research Use Only (RUO). This popular-science article summarizes published scientific knowledge. It constitutes neither a recommendation for use in humans or animals nor a therapeutic claim.
