Key takeaways
- Incretins (GLP-1 and GIP) amplify glucose-dependent insulin secretion; glucagon is their counter-regulatory partner.
- All three act through class B GPCRs that signal largely via cAMP.
- Single, dual and tri-agonists let researchers compare receptor combinations.
- The AH series covers one, two and three receptors.
Incretin-class peptides are among the most active areas of metabolic research. They are usually described by which receptors they act on: one, two or three. This primer explains those receptors and why researchers compare single-, dual- and tri-receptor agonists.
The three receptors
| Receptor | Main tissues | Research focus |
|---|---|---|
| GLP-1R | Pancreatic beta cells, brain, gut | Glucose-dependent insulin secretion, glucagon suppression, gastric emptying, appetite signaling |
| GIPR | Beta cells, adipose tissue, CNS | Insulin secretion, adipose lipid handling, interaction with GLP-1 signaling |
| GCGR | Liver (primarily) | Hepatic glucose output, lipid metabolism, energy expenditure |
What incretins are
Incretins are gut hormones released after a meal that amplify insulin secretion in a glucose-dependent way. The two classic incretins are GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). Glucagon is structurally related and is the main counter-regulatory hormone to insulin. All three act through class B G-protein-coupled receptors that signal largely through cyclic AMP.
Why combine receptors?
A central question in the field is how co-activating receptors compares with activating GLP-1R alone. Adding GIPR activity brings in adipose and insulin-secretion effects; adding GCGR activity extends research into hepatic energy expenditure and lipid metabolism, with incretin signaling offsetting glucagon’s effect on glucose.
Because the same peptide backbone can be tuned to favor one receptor or another, comparing compounds across a single-, dual- and tri-agonist series is a common experimental design.
The After Hours Labs incretin series
See the full set in Metabolic Pathway Research, and look up the batch-matched COA for any lot.
All After Hours Labs products are sold strictly for qualified in-vitro laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice or a recommendation for use in people or animals.
