To generate the recombinant human GIPR protein, the target gene encoding amino acids 22-138 of the human GIPR is expressed in mammalian cells using a plasmid system. The target gene is co-expressed with the C-terminal 10xHis-tag gene. The resulting GIPR protein's purity is up to 95% as determined by SDS-PAGE and SEC-HPLC. Its endotoxin level measured via the LAL method is less than 1.0 EU/μg. ELISA confirms the GIPR protein's biological activity through specific GIPR recombinant antibody (CSB-RA009438MA1HU) binding, with an EC50 of 16.18 to 18.70 ng/mL.
The human GIPR, also known as the glucose-dependent insulinotropic polypeptide receptor, is a GPCR that plays a crucial role in glucose metabolism and insulin secretion. GIPR is primarily activated by the incretin hormone gastric inhibitory polypeptide (GIP), which is secreted by K cells in the duodenum and proximal small intestine in response to nutrient ingestion, particularly carbohydrates and fats [1][2][3]. Upon activation, GIPR enhances insulin secretion from pancreatic β-cells, thereby contributing to the regulation of blood glucose levels [2][4].
Research has indicated that GIPR has implications for obesity and type 2 diabetes mellitus (T2DM). GIPR signaling has been linked to improved insulin sensitivity and lipid metabolism, which are critical in the context of obesity [5][6]. Furthermore, genetic variations in the GIPR gene have been associated with impaired glucose homeostasis and obesity phenotypes, suggesting a complex role of GIPR in metabolic disorders [7][4].
GIPR is also involved in various physiological processes beyond glucose regulation. It is expressed in several tissues, including adipose tissue and bone, where it influences bone cell metabolism and remodeling [8][9]. Studies have shown that GIPR is present in osteoblastic cell lines, indicating a potential role in bone health and metabolism [8][9]. Moreover, GIPR has been identified as a promising target for therapeutic interventions in neuroendocrine tumors, highlighting its relevance in cancer biology [10][11].
References:
[1] Y. Takahashi. Gastric inhibitory polypeptide receptor antagonism suppresses intramuscular adipose tissue accumulation and ameliorates sarcopenia, Journal of Cachexia Sarcopenia and Muscle, vol. 14, no. 6, p. 2703-2718, 2023. https://doi.org/10.1002/jcsm.13346
[2] S. Yamane and N. Harada. Gastric inhibitory polypeptide/glucose‐dependent insulinotropic polypeptide signaling in adipose tissue, Journal of Diabetes Investigation, vol. 10, no. 1, p. 3-5, 2018. https://doi.org/10.1111/jdi.12942
[3] Y. Yamada, K. Tsukiyama, T. Sato, T. Shimizu, H. Fujita, & T. Narita. Novel extrapancreatic effects of incretin, Journal of Diabetes Investigation, vol. 7, no. S1, p. 76-79, 2016. https://doi.org/10.1111/jdi.12495
[4] S. Erfanian, H. Mir, A. Abdoli, & A. Roustazadeh. Association of gastric inhibitory polypeptide receptor (gipr) gene polymorphism with type 2 diabetes mellitus in iranian patients, BMC Medical Genomics, vol. 16, no. 1, 2023. https://doi.org/10.1186/s12920-023-01477-z
[5] P. Mróz, B. Finan, V. Gelfanov, B. Yang, M. Tschöp, R. DiMarchi, et al. Optimized gip analogs promote body weight lowering in mice through gipr agonism not antagonism, Molecular Metabolism, vol. 20, p. 51-62, 2019. https://doi.org/10.1016/j.molmet.2018.12.001
[6] H. Kizilkaya, K. Sørensen, C. Kibsgaard, L. Gasbjerg, A. Hauser, A. Sparre-Ulrich, et al. Loss of function glucose-dependent insulinotropic polypeptide receptor variants are associated with alterations in bmi, bone strength and cardiovascular outcomes, Frontiers in Cell and Developmental Biology, vol. 9, 2021. https://doi.org/10.3389/fcell.2021.749607
[7] J. Sauber, J. Grothe, M. Behm, A. Scherag, H. Grallert, T. Illig, et al. Association of variants in gastric inhibitory polypeptide receptor gene with impaired glucose homeostasis in obese children and adolescents from berlin, Acta Endocrinologica, vol. 163, no. 2, p. 259-264, 2010. https://doi.org/10.1530/eje-10-0444
[8] M. Hansen, M. Tencerova, J. Frølich, M. Kassem, & M. Frost. Effects of gastric inhibitory polypeptide, glucagon‐like peptide‐1 and glucagon‐like peptide‐1 receptor agonists on bone cell metabolism, Basic & Clinical Pharmacology & Toxicology, vol. 122, no. 1, p. 25-37, 2017. https://doi.org/10.1111/bcpt.12850
[9] E. Aoyama, I. Watari, K. Podyma‐Inoue, M. Yanagishita, & T. Ono. Expression of glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor is regulated by the glucose concentration in mouse osteoblastic mc3t3-e1 cells, International Journal of Molecular Medicine, vol. 34, no. 2, p. 475-482, 2014. https://doi.org/10.3892/ijmm.2014.1787
[10] S. Sherman, J. Carr, D. Wang, M. O'Dorisio, T. O'Dorisio, & J. Howe. Gastric inhibitory polypeptide receptor (gipr) is a promising target for imaging and therapy in neuroendocrine tumors, Surgery, vol. 154, no. 6, p. 1206-1214, 2013. https://doi.org/10.1016/j.surg.2013.04.052
[11] A. Haase. Gastric inhibitory polypeptide receptor (gipr) overexpression reduces the tumorigenic potential of retinoblastoma cells, Cancers, vol. 16, no. 9, p. 1656, 2024. https://doi.org/10.3390/cancers16091656
