Skip to main content
SpringerLink
Log in

Hexane fraction of Citrus aurantium L. stimulates glucagon-like peptide-1 (GLP-1) secretion via membrane depolarization in NCI-H716 cells

  • Original Research
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

Citrus species have been used traditionally as a medicinal herb in oriental pharmacology. Here, we reported on the anti-diabetic function of Citrus aurantium L. (CA). The hexane fraction of CA (HFCA) stimulates NCI-H716 cells and results in the secretion of glucagon-like peptide-1 (GLP-1). Because it regulates insulin secretion in pancreatic β-cells, GLP-1 has been used for the treatment of type II diabetes mellitus. Hence, we carried out a series of experiments to demonstrate the functions of HFCA against diabetes mellitus at the molecular level. Four fractions of CA were used in a GLP-1 assay. The GLP-1 ELISA assay was performed to measure the concentrations of GLP-1 after treatment with the four fractions of CA. The hexane fraction showed the best results and was chosen for the microarray analysis in the genome wide analysis. Through the analysis, it was found that voltage-gated potassium (Kv) channels drove membrane depolarization and then influenced Ca2+ currents in NCIH716 cells. These results suggest this is a new oriental herbal drug that has proven effects for the remedy of type II diabetes mellitus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Le Neve, B. & Daniel, H. Selected tetrapeptides lead to a GLP-1 release from the human enteroendocrine cell line NCI-H716. Regul. Pept. 167, 14–20 (2011).

    Article  Google Scholar 

  2. Han, X.F., Zhu, Y.L., Hernandez, M., Keating, D.J., & Chen, C. Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways. Endocrine 28, 217–224 (2005).

    Article  CAS  Google Scholar 

  3. Kim, S.J. et al. Pancreatic beta-cell prosurvival effects of the incretin hormones involve post-translational modification of Kv2.1 delayed rectifier channels. Cell Death Differ. 19, 333–344 (2012).

    Article  CAS  Google Scholar 

  4. Jang, H.J. et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc. Natl. Acad. Sci. USA 104, 15069–15074 (2007).

    Article  CAS  Google Scholar 

  5. Duez, H., Cariou, B. & Staels, B. DPP-4 inhibitors in the treatment of type 2 diabetes. Biochem. Pharmacol. 83, 823–832 (2012).

    Article  CAS  Google Scholar 

  6. Pratley, R.E. & Gilbert, M., Targeting incretins in type 2 diabetes: role of GLP-1 receptor agonists and DPP-4 inhibitors. Rev. Diabet. Stud. 5, 73–94 (2008).

    Article  Google Scholar 

  7. Elashoff, M., Matveyenko, A.V., Gier, B., Elashoff, R. & Butler, P.C. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 141, 150–156 (2011).

    Article  CAS  Google Scholar 

  8. Choi, E.-K. et al. Genome-wide gene expression analysis of Patrinia scabiosaefolia reveals an antibiotic effect. BioChip J. 5, 246–254 (2011).

    Article  CAS  Google Scholar 

  9. Kim, K.-S. et al. The multi-target antibiotic efficacy of Angelica dahurica Bentham et Hooker extract exposed to the Escherichia coli O157:H7. 333–342.

  10. Yang, H. et al. Global transcriptome analysis of the E. coli O157 response to Agrimonia pilosa extract. Mol. Cell. Toxicol. 7, 299–310 (2011).

    Article  CAS  Google Scholar 

  11. Kim, K.-S. et al. Global transcriptome analysis of the Escherichia coli O157 response to Houttuynia Cordata Thunb. BioChip J. 4, 237–246 (2010).

    Article  CAS  Google Scholar 

  12. Avula, B., Upparapalli, S.K. & Khan, I.A. Enantiomeric separation of adrenergic amines in Citrus species, related genera and dietary supplements by capillary electrophoresis. Chromatographia 62, 151–157 (2005).

    Article  CAS  Google Scholar 

  13. Bennett, V. & Baines, A.J. Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. Physiol. Rev. 81, 1353–1392 (2001).

    CAS  Google Scholar 

  14. Stabach, P.R., Devarajan, P., Stankewich, M.C., Bannykh, S. & Morrow, J.S. Ankyrin facilitates intracellular trafficking of alpha1-Na+-K+-ATPase in polarized cells. Am. J. Physiol. Cell Physiol. 295, C1202–1214 (2008).

    Article  CAS  Google Scholar 

  15. Singleton, P.A. & Bourguignon, L.Y. CD44 interaction with ankyrin and IP3 receptor in lipid rafts promotes hyaluronan-mediated Ca2+ signaling leading to nitric oxide production and endothelial cell adhesion and proliferation. Exp. Cell Res. 295, 102–118 (2004).

    Article  CAS  Google Scholar 

  16. Tolhurst, G. et al. Glutamine triggers and potentiates glucagon-like peptide-1 secretion by raising cytosolic Ca2+ and cAMP. Endocrinology 152, 405–413 (2011).

    Article  CAS  Google Scholar 

  17. Chung, H.J., Jan, Y.N. & Jan, L.Y. Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains. Proc. Natl. Acad. Sci. USA 103, 8870–8875 (2006).

    Article  CAS  Google Scholar 

  18. Canaider, S. et al. Human RCAN3 gene expression and cell growth in endothelial cells. Int. J. Mol. Med. 26, 913–918 (2010).

    Article  CAS  Google Scholar 

  19. Heit, J.J. Calcineurin/NFAT signaling in the beta-cell: From diabetes to new therapeutics. Bioessays 29, 1011–1021 (2007).

    Article  CAS  Google Scholar 

  20. Hediger, M.A. et al. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction. Pflugers Arch. 447, 465–468 (2004).

    Article  CAS  Google Scholar 

  21. Ganz, M.B., Hawkins, K. & Reilly, R.F. High glucose induces the activity and expression of Na (+)/H (+) exchange in glomerular mesangial cells. Am. J. Physiol. Renal. Physiol. 278, F91–96 (2000).

    CAS  Google Scholar 

  22. Beloto-Silva, O., Machado, U.F. & Oliveira-Souza, M. Glucose-induced regulation of NHEs activity and SGLTs expression involves the PKA signaling pathway. J. Mem. Biol. 239, 157–165 (2011).

    Article  CAS  Google Scholar 

  23. Schulz, E. & Munzel, T. Intracellular pH: a fundamental modulator of vascular function. Circulation 124, 1806–1807 (2012).

    Article  Google Scholar 

  24. Vial, G. et al. Na+/H+ exchange inhibition with cariporide prevents alterations of coronary endothelial function in streptozotocin-induced diabetes. Mol. Cell. Biochem. 310, 93–102 (2008).

    Article  CAS  Google Scholar 

  25. Moulin, P. et al. Identification and subcellular localization of the Na+/H+ exchanger and a novel related proein in the endocrine pancreas and adrenal medulla. J. Mol. Endocrinol. 38, 409–422 (2007).

    Article  CAS  Google Scholar 

  26. Reimer, R.A. et al. A human cellular model for studying the regulation of glucagon-like peptide-1 secretion. Endocrinology 142, 4522–4528 (2001).

    Article  CAS  Google Scholar 

  27. Paul, S. et al. Impact of miRNA deregulation on mRNA expression profiles in response to environmental toxicant, nonylphenol. Mol. Cell. Toxicol. 7, 259–269 (2011).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dondaemun-gu, Seoul, 130-701, Korea

    Eun-Kyeong Choi, Ki-Suk Kim, Hea Jung Yang, Min-Hee Shin, Hyo-Weon Suh, Ki-Beom Lee, Kwang Seok Ahn, Jae Young Um, Seok-Geun Lee, Byung-Cheol Lee & Hyeung-Jin Jang

Authors
  1. Eun-Kyeong Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ki-Suk Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hea Jung Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Min-Hee Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyo-Weon Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ki-Beom Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kwang Seok Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jae Young Um
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Seok-Geun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Byung-Cheol Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hyeung-Jin Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hyeung-Jin Jang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choi, EK., Kim, KS., Yang, H.J. et al. Hexane fraction of Citrus aurantium L. stimulates glucagon-like peptide-1 (GLP-1) secretion via membrane depolarization in NCI-H716 cells. BioChip J 6, 41–47 (2012). https://doi.org/10.1007/s13206-012-6106-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-012-6106-7

Keywords

Search

Navigation