Apelin-13 analogues show potent in vitro and in vivo insulinotropic and glucose lowering actions
Journal article
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
| Authors | O'Harte, Finbarr P. M., Parthsarathy, Vadivel, Hogg, Christopher and Flatt, Peter R. |
|---|---|
| Abstract | Nine structurally modified apelin-13 analogues were assessed for their in vitro and acute in vivo antidiabetic potential. Stability was assessed in mouse plasma and insulinotropic efficacy tested in cultured pancreatic BRIN-BD11 cells and isolated mouse pancreatic islets. Intracellular Ca2+ and cAMP production in BRIN-BD11 cells was determined, as was glucose uptake in 3T3-L1 adipocytes. Acute antihyperglycemic effects of apelin analogues were assessed following i.p. glucose tolerance tests (ipGGT, 18 mmol/kg) in normal and diet-induced-obese (DIO) mice and on food intake in normal mice. Apelin analogues all showed enhanced in vitro stability (up to 5.8-fold, t½ = 12.8 h) in mouse plasma compared to native apelin-13 (t½ = 2.1 h). Compared to glucose controls, stable analogues exhibited enhanced insulinotropic responses from BRIN-BD11 cells (up to 4.7-fold, p < 0.001) and isolated mouse islets (up to 5.3-fold) for 10−7 M apelin-13 amide (versus 7.6-fold for 10−7 M GLP-1). Activation of APJ receptors on BRIN-BD11 cells increased intracellular Ca2+ (up to 3.0-fold, p < 0.001) and cAMP (up to 1.7-fold, p < 0.01). Acute ipGTT showed improved insulinotropic and glucose disposal responses in normal and DIO mice (p < 0.05 and p < 0.01, respectively). Apelin-13 amide and (pGlu)apelin-13 amide were the most effective analogues exhibiting acute, dose-dependent and persistent biological actions. Both analogues stimulated insulin-independent glucose uptake by differentiated adipocytes (2.9 to –3.3-fold, p < 0.05) and inhibited food intake (26-–33%, p < 0.001), up to 180 min in mice, versus saline. In contrast, (Ala13)apelin-13 and (Val13)apelin-13 inhibited insulin secretion, suppressed beta-cell signal transduction and stimulated food intake in mice. Thus, stable analogues of apelin-13 have potential for diabetes/obesity therapy. |
| Keywords | diabetes; insulin; glucose homeostasis |
| Year | 2018 |
| Journal | Peptides |
| Publisher | Elsevier |
| ISSN | 0196-9781 |
| Digital Object Identifier (DOI) | https://doi.org/10.1016/j.peptides.2017.12.004 |
| Web address (URL) | http://hdl.handle.net/10545/622904 |
| hdl:10545/622904 | |
| https://pure.ulster.ac.uk/en/publications/apelin-13-analogues-show-potent-in-vitro-and-in-vivo-insulinotrop | |
| Output status | Published |
| Publication dates | 03 Feb 2018 |
| Publication process dates | |
| Deposited | 16 Aug 2018 |
Permalink -
https://repository.derby.ac.uk/item/948wv/apelin-13-analogues-show-potent-in-vitro-and-in-vivo-insulinotropic-and-glucose-lowering-actions
42
total views0
total downloads1
views this month0
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/msf2023023001Exendin-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/10.1080/15548627.2021.1956123Protein 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.2021.16292Stability 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.14615Macroalgal 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.2019.110695Beneficial 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.13068Metabolic 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-17-0263Acylated 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.2017.10.002Long-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.0202350Atlantic 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.2018.01.025Boarfish (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-1Metabolic 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-17-0263An 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-yBlue 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.2017.10.045Beneficial 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