Biological Activity and Antidiabetic Potential of C-Terminal Octapeptide Fragments of the Gut-Derived Hormone Xenin

Journal article


Martin, Christine M., Parthsarathy, Vadivel, Hasib, Annie, NG, Ming T., McClean, Stephen, Flatt, Peter R., Gault, Victor A. and Irwin, Nigel 2016. Biological Activity and Antidiabetic Potential of C-Terminal Octapeptide Fragments of the Gut-Derived Hormone Xenin. PLos ONE. 11 (3). https://doi.org/10.1371/journal.pone.0152818
AuthorsMartin, Christine M., Parthsarathy, Vadivel, Hasib, Annie, NG, Ming T., McClean, Stephen, Flatt, Peter R., Gault, Victor A. and Irwin, Nigel
Abstract

Xenin is a peptide that is co-secreted with the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), from intestinal K-cells in response to feeding. Studies demonstrate that xenin has appetite suppressive effects and modulates glucose-induced insulin secretion. The present study was undertaken to determine the bioactivity and antidiabetic properties of two C-terminal fragment xenin peptides, namely xenin 18-25 and xenin 18-25 Gln. In BRIN-BD11 cells, both xenin fragment peptides concentration-dependently stimulated insulin secretion, with similar efficacy as the parent peptide. Neither fragment peptide had any effect on acute feeding behaviour at elevated doses of 500 nmol/kg bw. When administered together with glucose to normal mice at 25 nmol/kg bw, the overall insulin secretory effect was significantly enhanced in both xenin 18-25 and xenin 18-25 Gln treated mice, with better moderation of blood glucose levels. Twice daily administration of xenin 18-25 or xenin 18-25 Gln for 21 days in high fat fed mice did not affect energy intake, body weight, circulating blood glucose or body fat stores. However, circulating plasma insulin concentrations had a tendency to be elevated, particularly in xenin 18-25 Gln mice. Both treatment regimens significantly improved insulin sensitivity by the end of the treatment period. In addition, sustained treatment with xenin 18-25 Gln significantly reduced the overall glycaemic excursion and augmented the insulinotropic response to an exogenous glucose challenge on day 21. In harmony with this, GIP-mediated glucose-lowering and insulin-releasing effects were substantially improved by twice daily xenin 18-25 Gln treatment. Overall, these data provide evidence that C-terminal octapeptide fragments of xenin, such as xenin 18-25 Gln, have potential therapeutic utility for type 2 diabetes.

Keywordsdiabetes; antihyperglycaemic; peptide fragments
Year2016
JournalPLos ONE
Journal citation11 (3)
PublisherPublic Library of Science (PLoS)
ISSN1932-6203
Digital Object Identifier (DOI)https://doi.org/10.1371/journal.pone.0152818
Web address (URL)http://hdl.handle.net/10545/622907
hdl:10545/622907
http://europepmc.org/article/med/27032106
Output statusPublished
Publication dates31 Mar 2016
Publication process dates
Deposited16 Aug 2018
Permalink -

https://repository.derby.ac.uk/item/932yw/biological-activity-and-antidiabetic-potential-of-c-terminal-octapeptide-fragments-of-the-gut-derived-hormone-xenin

  • 22
    total views
  • 0
    total downloads
  • 0
    views this month
  • 0
    downloads this month

Export as

Related outputs

Peptide Co-Agonists for Combined Activation of the APJ and GLP-1 Receptors with Insulinotropic and Satiety Actions Show Potential for Alleviation of Metabolic Dysfunction in Type 2 Diabetes †
O' Harte, S., Parthsarathy, V., Craig, S., Palmer, E. and Irwin, N. 2023. Peptide Co-Agonists for Combined Activation of the APJ and GLP-1 Receptors with Insulinotropic and Satiety Actions Show Potential for Alleviation of Metabolic Dysfunction in Type 2 Diabetes †. 1st International Meeting Molecules 4 Life. MDPI. https://doi.org/10.3390/msf2023023001
Exendin-4 stimulates autophagy in pancreatic β-cells via the RAPGEF/EPAC-Ca PPP3/calcineurin-TFEB axis
Zummo, F.P, Krishnanda, S.I, Georgiou, M., O’Harte, F. P. M., Parthsarathy, V., Cullen, K.S, Honkanen-Scott, M, Shaw, J.A.M, Lovat, P.E and Arden, C 2021. Exendin-4 stimulates autophagy in pancreatic β-cells via the RAPGEF/EPAC-Ca PPP3/calcineurin-TFEB axis. Autophagy. 18 (4), pp. 1-17. https://doi.org/10.1080/15548627.2021.1956123
Protein hydrolysates from boarfish (Capros aper) and Atlantic salmon (Salmo salar) skin gelatin improve metabolic control in genetically obese diabetic (ob/ob) mice
Parthsarathy, V., McLaughlin, C.M, Sharkey, S.J, Harnedy-Rothwell, P.A, Lafferty, R.A, Allsopp, P.J, McSorley, E.M, Fitzgerald, R.J and O'Harte, F.P.M 2021. Protein hydrolysates from boarfish (Capros aper) and Atlantic salmon (Salmo salar) skin gelatin improve metabolic control in genetically obese diabetic (ob/ob) mice. Journal of Food Bioactives. 16, pp. 48-57. https://doi.org/10.31665/JFB.2021.16292
Stability to thermal treatment of dipeptidyl peptidase‐IV inhibitory activity of a boarfish (Capros aper) protein hydrolysate when incorporated into tomato‐based products
Harnedy‐Rothwell, P.A., McLaughlin, C.M., Crowe, W., Allsopp, P.J., McSorley, E.M., Devaney, M., Whooley, J., McGovern, B., Parthsarathy, V., O'Harte, F.P.M. and FitzGerald, R.J. 2021. Stability to thermal treatment of dipeptidyl peptidase‐IV inhibitory activity of a boarfish (Capros aper) protein hydrolysate when incorporated into tomato‐based products. International Journal of Food Science and Technology. 56 (1), pp. 158-165. https://doi.org/10.1111/ijfs.14615
Macroalgal protein hydrolysates from Palmaria palmata influence the 'incretin effect' in vitro via DPP-4 inhibition and upregulation of insulin, GLP-1 and GIP secretion
McLaughlin, C.M., Harnedy-Rothwell, P.A., Lafferty, R.A., Sharkey, S., Parthsarathy, V., Allsopp, P.J., McSorley, E.M., FitzGerald, R.J. and O'Harte, F.P.M. 2021. Macroalgal protein hydrolysates from Palmaria palmata influence the 'incretin effect' in vitro via DPP-4 inhibition and upregulation of insulin, GLP-1 and GIP secretion. European Journal of Nutrition. 60 (8), pp. 4439-4452. https://doi.org/10.1007/s00394-021-02583-3
Chronic apelin analogue administration is more effective than established incretin therapies for alleviating metabolic dysfunction in diabetic db/db mice
O'Harte, Finbarr P M, Parthsarathy, Vadivel and Flatt, Peter R 2020. Chronic apelin analogue administration is more effective than established incretin therapies for alleviating metabolic dysfunction in diabetic db/db mice. Molecular and cellular endocrinology. 504, p. 110695. https://doi.org/10.1016/j.mce.2019.110695
Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice.
Parthsarathy, Vadivel, Hogg, Christopher, Flatt, Peter R. and O'Harte, Finbarr P. M. 2017. Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice. Diabetes Obesity and Metabolism. https://doi.org/10.1111/dom.13068
Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice
Millar, Paul, Pathak, Nupur, Parthsarathy, Vadivel, Bjourson, Anthony J., O'Kane, Maurice, Pathak, Varun, Moffett, Charlotte, Flatt, Peter R. and Gault, Victor A. 2017. Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice. Journal of Endocrinology. https://doi.org/10.1530/JOE-17-0263
Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties
O'Harte, Finbarr P. M., Parthsarathy, Vadivel, Hogg, Christopher and Flatt, Peter R. 2017. Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties. Biochemical pharmacology. https://doi.org/10.1016/j.bcp.2017.10.002
Apelin-13 analogues show potent in vitro and in vivo insulinotropic and glucose lowering actions
O'Harte, Finbarr P. M., Parthsarathy, Vadivel, Hogg, Christopher and Flatt, Peter R. 2018. Apelin-13 analogues show potent in vitro and in vivo insulinotropic and glucose lowering actions. Peptides. https://doi.org/10.1016/j.peptides.2017.12.004
Long-term treatment with acylated analogues of apelin-13 amide ameliorates diabetes and improves lipid profile of high-fat fed mice.
O' Harte, F.P.M., Parthsarathy, V., Hogg, C and Flatt, P 2018. Long-term treatment with acylated analogues of apelin-13 amide ameliorates diabetes and improves lipid profile of high-fat fed mice. PLos ONE. 13 (8). https://doi.org/10.1371/journal.pone.0202350
Atlantic salmon (Salmo salar) co-product-derived protein hydrolysates: A source of antidiabetic peptides
Harnedy, Pàdraigín A., Parthsarathy, Vadivel, McLaughlin, Chris M., O'Keeffe, Martina B., Allsopp, Philip J., McSorley, Emeir M., O'Harte, Finbarr P. M. and FitzGerald, Richard J. 2018. Atlantic salmon (Salmo salar) co-product-derived protein hydrolysates: A source of antidiabetic peptides. Food Research International. 106, pp. 598-606. https://doi.org/10.1016/j.foodres.2018.01.025
Boarfish (Capros aper) protein hydrolysate has potent insulinotropic and GLP‐1 secretory activity in vitro and acute glucose lowering effects in mice
Parthsarathy, Vadivel, Mclaughlin, Christopher, Harnedy, Padraigin, Allsopp, Phillip, Crowe, William, McSorley, Emeir, FitzGerald, Dick and O'Harte, Finbarr 2018. Boarfish (Capros aper) protein hydrolysate has potent insulinotropic and GLP‐1 secretory activity in vitro and acute glucose lowering effects in mice. International Journal of Food Science and Technology. 54 (1), pp. 271-281. https://doi.org/10.1111/ijfs.2019.54.issue-1
Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice
Millar, P., Pathak, N., Parthsarathy, V., Bjourson, A.J., O'Kane, M., Pathak, V., Moffett, R.C., Flatt, P.R. and Gault, V.A. 2017. Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice. The Journal of Endocrinology. 234 (3), pp. 255-267. https://doi.org/10.1530/joe-17-0263
An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice
Hasib, Annie, Ng, Tony, Gault, Victor A., Khan, Dawood, Parthsarathy, Vadivel, Flatt, Peter and Irwin, Nigel 2017. An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice. Diabetologia. 60 (2017), pp. 541-552. https://doi.org/10.1007/s00125-016-4186-y
Blue whiting (Micromesistius poutassou) muscle protein hydrolysate with in vitro and in vivo antidiabetic properties
Harnedy, Pàdraigín A., Parthsarathy, Vadivel, McLaughlin, Chris M., O'Keeffe, Martina B., Allsopp, Philip J., McSorley, Emeir M., O'Harte, Finbarr P. M. and Fitzgerald, Richard J. 2017. Blue whiting (Micromesistius poutassou) muscle protein hydrolysate with in vitro and in vivo antidiabetic properties. Journal of Functional Foods. 40 (2018), pp. 137-145. https://doi.org/10.1016/j.jff.2017.10.045
Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice
Parthsarathy, Vadivel, Hogg, Christopher, Flatt, Peter R. and O'Harte, Finbarr P. M. 2017. Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice. Diabetes Obesity and Metabolism. 20 (2), pp. 319-327. https://doi.org/10.1111/dom.13068
Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties
O'Harte, Finbarr P M, Parthsarathy, Vadivel, Hogg, Christopher and Flatt, Peter R 2017. Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties. Biochemical pharmacology. 146, pp. 165-173. https://doi.org/10.1016/j.bcp.2017.10.002
A novel chemically modified analogue of xenin-25 exhibits improved glucose-lowering and insulin-releasing properties
Parthsarathy, Vadivel, Irwin, Nigel, Hasib, Annie, Martin, Christine M., McClean, Stephen, Bhat, Vikas K., NG, Ming T., Flatt, Peter R. and Gault, Victor A. 2016. A novel chemically modified analogue of xenin-25 exhibits improved glucose-lowering and insulin-releasing properties. Biochimica et Biophysica Acta. 1860 (4), pp. 757-764. https://doi.org/10.1016/j.bbagen.2016.01.015
Xenin-25[Lys(13)PAL]: a novel long-acting acylated analogue of xenin-25 with promising antidiabetic potential
Gault, Victor A., Martin, Christine M., Flatt, Peter R., Parthsarathy, Vadivel and Irwin, Nigel 2015. Xenin-25[Lys(13)PAL]: a novel long-acting acylated analogue of xenin-25 with promising antidiabetic potential. Acta Diabetologica. 52 (3), pp. 461-471. https://doi.org/10.1007/s00592-014-0681-0
Characterisation of the biological activity of xenin-25 degradation fragment peptides
Martin, C.M., Parthsarathy, V., Pathak, V., Gault, V.A., Flatt, P.R. and Irwin, N. 2014. Characterisation of the biological activity of xenin-25 degradation fragment peptides. The Journal of Endocrinology. 221 (2), pp. 193-200. https://doi.org/10.1530/joe-13-0617
Correction: A Novel Retro-Inverso Peptide Inhibitor Reduces Amyloid Deposition, Oxidation and Inflammation and Stimulates Neurogenesis in the APPswe/PS1ΔE9 Mouse Model of Alzheimer’s Disease
Parthsarathy, V., McClean, P.L., Hölscher, C., Taylor, M., Tinker, C., Jones, G., Kolosov, O., Salvati, E., Gregori, M., Masserini, M. and Allsop, D. 2013. Correction: A Novel Retro-Inverso Peptide Inhibitor Reduces Amyloid Deposition, Oxidation and Inflammation and Stimulates Neurogenesis in the APPswe/PS1ΔE9 Mouse Model of Alzheimer’s Disease. PLos ONE. 8 (9). https://doi.org/10.1371/annotation/57e0a947-8600-4658-b04c-cf7a45c8bd8d
A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease
Parthsarathy, V., McClean, P.L., Hölscher, C., Taylor, M., Tinker, C., Jones, G., Kolosov, O., Salvati, E., Gregori, M., Masserini, M. and Allsop, D. 2013. A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease. PLos ONE. 8 (1). https://doi.org/10.1371/journal.pone.0054769
Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model
Parthsarathy, V. and Hölscher, C. 2013. Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model. PLos ONE. 8 (3). https://doi.org/10.1371/journal.pone.0058784
The type 2 diabetes drug liraglutide reduces chronic inflammation induced by irradiation in the mouse brain
Parthsarathy, Vadivel and Holscher, Christian 2013. The type 2 diabetes drug liraglutide reduces chronic inflammation induced by irradiation in the mouse brain. European Journal of Pharmacology. 700 (1-3), pp. 42-50. https://doi.org/10.1016/j.ejphar.2012.12.012
The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease
McClean, P.L., Parthsarathy, V,, Faivre, E. and Hölscher, C. 2011. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease. The Journal of Neuroscience. 31 (17), pp. 6587-6594. https://doi.org/10.1523/jneurosci.0529-11.2011