GIPR Functional Cell-based Agonist Assay for compound screening and profiling via cAMP production measured by FRET technology.
GIPR is the receptor for glucose-dependent insulinotropic polypeptide (GIP), an incretin hormone secreted by enteroendocrine K-cells of the small intestine in response to nutrient intake. Upon activation by GIP, GIPR primarily couples to Gs proteins and stimulates adenylate cyclase activity, resulting in increased intracellular cAMP levels and activation of downstream signaling pathways. GIPR signaling plays a key role in glucose homeostasis by enhancing glucose-dependent insulin secretion from pancreatic β-cells. In addition, GIPR activation has been associated with effects on lipid metabolism, adipose tissue function, energy balance, and overall metabolic regulation. Therapeutic ligands such as Tirzepatide, a dual GIPR/GLP1R agonist, are pharmaceutically developed to treat type 2 diabetes mellitus and obesity.
GIPR
Gastric inhibitory polypeptide receptor; Glucose-dependent insulinotropic polypeptide receptor
HEK293
Transfected
HEK293 cells were transduced with the human glucose-dependent insulinotropic polypeptide receptor (GIPR). Stimulation of these cells with Tirzepatide, a dual GIPR and GLP-1R agonist with potent activity at GIPR, results in agonistic activation of cAMP production, which can be measured by FRET technology. Increased intracellular cAMP levels lead to a reduction of the FRET signal. The assay has been validated based on flow cytometric detection of target expression on cells and functional responses to a known GIPR agonist.
Induction of cAMP release
| Compound | EC50 |
|---|---|
| Tirzepatide | 25 pM |
Freiburg
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Reference compound activation of GIPR
Tirzepatide is known to specifically activate the cAMP response as an agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR). cAMP levels were measured by FRET technology. The agonist was included in the validation process, and the cellular GIPR assay generated highly reproducible EC50 values. The graph shows a representative result. A cAMP standard dose-response curve was generated in parallel.