The type 2 diabetes drug liraglutide reduces chronic inflammation induced by irradiation in the mouse brain
Journal article
Authors | Parthsarathy, Vadivel and Holscher, Christian |
---|---|
Abstract | Chronic inflammation in the brain is found in a range of neurodegenerative diseases such as Parkinson's or Alzheimer's disease. We have recently shown that analogues of the glucagon-like polypeptide 1 (GLP-1) such as liraglutide have potent neuroprotective properties in a mouse model of Alzheimer's disease. We also found a reduction of activated microglia in the brain. This finding suggests that GLP-1 analogues such as liraglutide have anti-inflammatory properties. To further characterise this property, we tested the effects of liraglutide on the chronic inflammation response induced by exposure of the brain to 6 Gy (X-ray). Animals were injected i.p. with 25 nmol/kg once daily for 30 days. Brains were analysed for cytokine levels, activated microglia and astrocyte levels, and nitrite levels as a measure for nitric oxide production and protein expression of iNOS. Exposure of the brain to 6 Gy induced a pronounced chronic inflammation response in the brain. The activated microglia load in the cortex and dentate gyrus region of hippocampus (P<0.001), and the activated astrocyte load in the cortex (P<0.01) was reduced by liraglutide. Furthermore, the pro-inflammatory cytokine levels of IL-6 (P<0.01), IL-12p70 (P<0.01), IL-1β (P<0.05), and total nitrite concentration were reduced in the brains of animals treated with liraglutide. The results demonstrate that liraglutide is effective in reducing a number of parameters linked to the chronic inflammation response. Liraglutide or similar GLP-1 analogues may be a suitable treatment for reducing the chronic inflammatory response in the brain found in several neurodegenerative conditions. |
Keywords | neurodegenerative diseases; Alzheimer's disease; Parkinson's disease; infection; incretins; liraglutide |
Year | 2013 |
Journal | European Journal of Pharmacology |
Journal citation | 700 (1-3), pp. 42-50 |
Publisher | Elsevier |
ISSN | 0014-2999 |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.ejphar.2012.12.012 |
Web address (URL) | http://hdl.handle.net/10545/622910 |
hdl:10545/622910 | |
http://europepmc.org/article/med/23276669 | |
Output status | Published |
Publication dates | 28 Dec 2012 |
Publication process dates | |
Deposited | 16 Aug 2018 |
https://repository.derby.ac.uk/item/94ww0/the-type-2-diabetes-drug-liraglutide-reduces-chronic-inflammation-induced-by-irradiation-in-the-mouse-brain
32
total views0
total downloads2
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.2017.10.002Apelin-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.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.2018.01.025
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-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.2017.10.045
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