Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Apr 7:10:1170181.
doi: 10.3389/fmolb.2023.1170181. eCollection 2023.

Variation in responses to incretin therapy: Modifiable and non-modifiable factors

Gregory O Austin  1 , Alejandra Tomas  1
Affiliations
Review

Variation in responses to incretin therapy: Modifiable and non-modifiable factors

Gregory O Austin et al. Front Mol Biosci. .

Abstract

Type 2 diabetes (T2D) and obesity have reached epidemic proportions. Incretin therapy is the second line of treatment for T2D, improving both blood glucose regulation and weight loss. Glucagon-like peptide-1 (GLP-1) and glucose-stimulated insulinotropic polypeptide (GIP) are the incretin hormones that provide the foundations for these drugs. While these therapies have been highly effective for some, the results are variable. Incretin therapies target the class B G protein-coupled receptors GLP-1R and GIPR, expressed mainly in the pancreas and the hypothalamus, while some therapeutical approaches include additional targeting of the related glucagon receptor (GCGR) in the liver. The proper functioning of these receptors is crucial for incretin therapy success and here we review several mechanisms at the cellular and molecular level that influence an individual's response to incretin therapy.

Keywords: GIP (glucose-dependent insulinotropic polypeptide); GLP-1 (glucagon-like peptide-1); T2D (type 2 diabetes); incretin receptors; incretin—based therapy; obesity.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Incretin receptor expression and proposed GPCR functional interactions.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Al-Zaid B., Chacko S., Ezeamuzie C. I., Bünemann M., Krasel C., Karimian T., et al. (2022). Differential effects of glucose-dependent insulinotropic polypeptide receptor/glucagon-like peptide-1 receptor heteromerization on cell signaling when expressed in HEK-293 cells. Pharmacol. Res. Perspect. 10, e01013. 10.1002/prp2.1013 - DOI - PMC - PubMed
    1. Ambery P., Parker V. E., Stumvoll M., Posch M. G., Heise T., Plum-Moerschel L., et al. (2018). MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: A randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet 391, 2607–2618. 10.1016/S0140-6736(18)30726-8 - DOI - PubMed
    1. Anton S. E., Kayser C., Maiellaro I., Nemec K., Möller J., Koschinski A., et al. (2022). Receptor-associated independent cAMP nanodomains mediate spatiotemporal specificity of GPCR signaling. Cell 185, 1130–1142.e11. 10.1016/j.cell.2022.02.011 - DOI - PubMed
    1. Apovian C. M., Okemah J., O’Neil P. M. (2019). Body weight considerations in the management of type 2 diabetes. Adv. Ther. 36, 44–58. 10.1007/s12325-018-0824-8 - DOI - PMC - PubMed
    1. Arcones A. C., Vila-Bedmar R., Mirasierra M., Cruces-Sande M., Vallejo M., Jones B., et al. (2021). GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo . BMC Biol. 19, 40. 10.1186/s12915-021-00966-w - DOI - PMC - PubMed

LinkOut - more resources