Keywords
Glucagon-like peptide-1 receptor agonist
Protection of organs
Submitted : 2023-07-01
Accepted : 2023-07-16
Published : 2023-07-31
Abstract
Glucagon-like peptide-1 (GLP-1) is a multifunctional hormone with broad pharmacological potential to control inflammation, protect cardiovascular, kidney, and liver functions. Moreover, GLP-1 can also cross the blood-brain barrier and bind with GLP-1R distributed in various parts of the brain, thereby reducing apoptosis caused by neuroinflammation and oxygen stress, and promoting learning, memory, cognitive function, neuroprotection, and nerve cell remodeling. However, the exact molecular pathway by which GLP-1 receptor agonists (GLP-1RAs) exerts protective effects on many organs is not fully understood, so it is a hot topic of research. In this article, the recent research on the multi-organ protection of GLP-1 is reviewed, with emphasis on the research progress in the field of nervous system and perioperative anesthesia.
References
Gribble FM, Reimann F, 2021, Metabolic Messengers: glucagon-like peptide 1. Nat Metab, 3(2): 142-148. https://www.doi.org/10.1038/s42255-020-00327-x
Muller TD, Finan B, Bloom SR, et al., 2019, Glucagon-like peptide 1 (GLP-1). Mol Metab 30: 72–130. https://www.doi.org/10.1016/j.molmet.2019.09.010
Richards P, Parker HE, Adriaenssens AE, et al., 2014, Identification and Characterization of GLP-1 Receptor-Expressing Cells Using a New Transgenic Mouse Model. Diabetes, 63(4): 1224–1233. https://www.doi.org/10.2337/db13-1440
Baggio LL, Yusta B, Mulvihill EE, et al., 2018, GLP-1 Receptor Expression Within the Human Heart. Endocrinology, 159(4): 1570–1584. https://www.doi.org/10.1210/en.2018-00004
He S, Kahles F, Rattik S, et al., 2019, Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease. Nature, 566(7742): 115–119. https://www.doi.org/10.1038/s41586-018-0849-9
Marx N, Davies MJ, Grant PJ, et al., 2021, Guideline Recommendations and the Positioning of Newer Drugs in Type 2 Diabetes Care. Diabetes & Endocrinology, 9(1): 46–52. https://www.doi.org/10.1016/S2213-8587(20)30343-0
Shi Q, Y. Wang Q, et al., 2021, Pharmacotherapy for Adults with Overweight and Obesity: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials. Lancet, 399(10321): 259–269. https://www.doi.org/10.1016/s0140-6736(21)01640-8
McLean BA, Wong CK, Campbell JE, et al., 2021, Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation. Endocr Rev, 42(2): 101–132. https://www.doi.org/10.1210/endrev/bnaa032
Sattar N, Lee MMY, Kristensen SL, et al., 2021, Cardiovascular, Mortality, and Kidney Outcomes with GLP-1 Receptor Agonists in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Trials. The Lancet Diabetes & Endocrinology 9(10): 653–662. https://www.doi.org/10.1016/s2213-8587(21)00203-5
Newsome PN, Buchholtz K, Cusi K, et al., A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med 2021, 384(12): 1113–1124. https://www.doi.org/10.1056/NEJMoa2028395.
Markaki I, Winther K, Catrina SB, et al., 2020, Repurposing GLP1 Agonists for Neurodegenerative Diseases. Int Rev Neurobiol 155: 91–112. https://www.doi.org/10.1016/bs.irn.2020.02.007
Tomas A, Jones B, Leech C, 2020, New Insights into Beta-Cell GLP-1 Receptor and cAMP Signaling. J Mol Biol, 432(5): 1347–1366. https://www.doi.org/10.1016/j.jmb.2019.08.009
Starling S, 2022, GLP1 acts on an inter-organ neural circuit. Nat Rev Endocrinol, 18(8): 455. https://www.doi.org/10.1038/s41574-022-00714-2
Wong CK, Yusta B, Koehler JA, et al., Divergent Roles for The Gut Intraepithelial Lymphocyte GLP-1R in Control of Metabolism, Microbiota, and T Cell-Induced Inflammation. Cell Metab, 34(10): 1514–1531. https://www.doi.org/10.1016/j.cmet.2022.08.003
Chambers AP, Sorrell JE, Haller A, et al., 2017, The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice. Cell Metab, 25(4): 927–934. https://www.doi.org/10.1016/j.cmet.2017.02.008
Davis EM, Sandoval DA, 2020, Glucagon-Like Peptide-1: Actions and Influence on Pancreatic Hormone Function. Compr Physiol, 10(2): 577–595. https://www.doi.org/10.1002/cphy.c190025
Zummo FP, Krishnanda SI, Georgiou M, et al., 2022, Exendin-4 Stimulates Autophagy in Pancreatic ?-Cells via the RAPGEF/EPAC-Ca(2+)-PPP3/Calcineurin-TFEB Axis. Autophagy, 18(4): 799–815. https://www.doi.org/10.1080/15548627.2021.1956123
Del Blanco BG, Otaegui I, Rodríguez-Palomares JF, et al., 2021, Effect of Combination Therapy with Remote Ischemic Conditioning and Exenatide on the Myocardial Infarct Size: A Two-by-Two Factorial Randomized Trial (COMBAT-MI). Basic Res Cardiol, 116: 4. https://www.doi.org/10.1007/s00395-021-00842-2
Honka H, Solis-Herrera C, Triplitt C, et al., 2021, Therapeutic Manipulation of Myocardial Metabolism: JACC State-of-the-Art Review. J Am Coll Cardiol, 77(16): 2022–2039. https://www.doi.org/10.1016/j.jacc.2021.02.057
Wright AK, Carr MJ, Kontopantelis E, et al., 2022, Primary Prevention of Cardiovascular and Heart Failure Events with SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes. Diabetes Care, 45(4): 909–918. https://www.doi.org/10.2337/dc21-1113
Cui X, Wei X, Yan W, et al., 2002, Research Progress on the Protective Mechanism of Glucagon-Like Peptide-1 Receptor Agonists. Chinese Journal of New Medicine, 31(14): 1367–1371.
McGuire DK, Pagidipati NJ, 2021, GLP1 Receptor Agonists: From Antihyperglycaemic to Cardiovascular Drugs. Lancet Diabetes Endocrinol, 9(10): 640–641. https://www.doi.org/10.1016/S2213-8587(21)00212-6
Muskiet MHA, Tonneijck L, Smits MM, et al., 2017, GLP-1 and the Kidney: From Physiology to Pharmacology and Outcomes in Diabetes. Nat Rev Nephrol 13(10): 605–628. https://www.doi.org/10.1038/nrneph.2017.123
Tonneijck L, Muskiet MHA, Smits MM, et al., 2018, Effect of Immediate and Prolonged GLP-1 Receptor Agonist Administration on Uric Acid and Kidney Clearance: Post-Hoc Analyses of Four Clinical Trials. Diabetes Obes Metab, 20(5): 1235–1245. https://www.doi.org/10.1111/dom.13223
Alicic RZ, Cox EJ, Neumiller JJ, et al., 2021, Incretin Drugs in Diabetic Kidney Disease: Biological Mechanisms and Clinical Evidence. Nat Rev Nephrol, 17(4): 227–244. https://www.doi.org/10.1038/s41581-020-00367-2
Kawanami D, Takashi Y, 2020, GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Clinical Outcomes to Mechanisms. Front Pharmacol, 11: 967. https://www.doi.org/10.3389/fphar.2020.00967
Jarvie BC, Knight ZA, 2022, Breaking Down A Gut-to-Brain Circuit That Prevents Malabsorption. Cell. 185(14): 2393–2395. https://www.doi.org/10.1016/j.cell.2022.06.012
Hira T, JPinyo and H. Hara What Is GLP-1 Really Doing in Obesity? Trends Endocrinol Metab 2020, 31(2): 71-80. https://www.doi.org/10.1016/j.tem.2019.09.003.
Chaudhari SN, Harris NA, Aliakbarian H, et al., 2021, Bariatric Surgery Reveals a Gut-Restricted TGR5 Agonist with Anti-Diabetic Effects. Nat Chem Biol 2021, 17(1): 20–29. https://www.doi.org/10.1038/s41589-020-0604-z
Hunt JE, Holst JJ, Jeppesen PB, et al., 2021, GLP-1 and Intestinal Diseases. Biomedicines 9(4): 383. https://www.doi.org/10.3390/biomedicines9040383
Foer D, Beeler PE, Cui J, et al., 2021, Asthma Exacerbations in Patients with Type 2 Diabetes and Asthma on Glucagon-like Peptide-1 Receptor Agonists. Am J Respir Crit Care Med, 203(7): 831–840. https://www.doi.org/10.1164/rccm.202004-0993OC
Albogami Y, Cusi K, Daniels MJ, et al., 2021, Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Exacerbations Among Patients with Type 2 Diabetes. Diabetes Care, 44(6): 1344–1352. https://www.doi.org/10.2337/dc20-1794
Liu J, Li X, Lu S, et al., 2021, Glucagon-like peptide-1 (GLP-1) improved diabetic lung fibrosis via AMPK and microRNA-27a (miR-27a). Ann Transl Med 2021, 9(6): 492. https://www.doi.org/10.21037/atm-21-869
Toki S, Newcomb DC, Printz RL, et al., 2021, Glucagon-like Peptide-1 Receptor Agonist Inhibits Aeroallergen-Induced Activation of ILC2 and Neutrophilic Airway Inflammation in Obese Mice. Allergy, 76(11): 3433–3445. https://www.doi.org/10.1111/all.14879
Lee JH, 2022, Potential Therapeutic Effect of Glucagon-Like Peptide-1 Receptor Agonists on COVID-19-Induced Pulmonary Arterial Hypertension. Medical Hypotheses, 158: 110739. https://www.doi.org/10.1016/j.mehy.2021.110739
Wang M, Yoon G, Song J, et al., 2021, Exendin-4 Improves Long-Term Potentiation and Neuronal Dendritic Growth In Vivo and In Vitro Obesity Condition. Sci Rep, 11(1): 8326. https://www.doi.org/10.1038/s41598-021-87809-4
Cai XS, Tan ZG, Li JJ, et al., 2017, Glucagon-Like Peptide-1 (GLP-1) Treatment Ameliorates Cognitive Impairment by Attenuating Arc Expression in Type 2 Diabetic Rats. Med Sci Monit, 23: 4334–4342. https://www.doi.org/10.12659/msm.903252
Yang Y, Fang H, Xu G, et al., 2018, Liraglutide Improves Cognitive Impairment via the AMPK and PI3K/Akt Signaling Pathways in type 2 Diabetic Rats. Mol Med Rep, 18(2): 2449–2457. https://www.doi.org/10.3892/mmr.2018.9180
Zhang H, Chu Y, Zheng H, et al., 2020, Liraglutide Improved the Cognitive Function of Diabetic Mice via the Receptor of Advanced Glycation End Products Down-Regulation. Aging (Albany NY) 13(1): 525–536. https://www.doi.org/10.18632/aging.202162
Saad MA, Eltarzy MA, Abdel Salam RM, et al., 2021, Liraglutide Mends Cognitive Impairment by Averting Notch Signaling Pathway Overexpression in a Rat Model of Polycystic Ovary Syndrome. Life Sci, 265: 118731. https://www.doi.org/10.1016/j.lfs.2020.118731
Bomba M, Granzotto A, Castelli V, et al., 2018, Exenatide Exerts Cognitive Effects by Modulating the BDNF-TrkB Neurotrophic Axis in Adult Mice. Neurobiol Aging 64: 33–43. https://www.doi.org/10.1016/j.neurobiolaging.2017.12.009
Li Q, Jia M, Yan Z, et al., 2021, Activation of Glucagon-Like Peptide-1 Receptor Ameliorates Cognitive Decline in Type 2 Diabetes Mellitus Through a Metabolism-Independent Pathway. J Am Heart Assoc, 10(14): e020734. https://www.doi.org/10.1161/jaha.120.020734
Dybjer EG, Engström C, Helmer, et al., 2020, Incretin Hormones, Insulin, Glucagon and Advanced Glycation End Products in Relation to Cognitive Function in Older People with and Without Diabetes, A Population-Based Study. Diabet Med 37(7): 1157–1166. https://www.doi.org/10.1111/dme.14267
Zhang Z, Zhang B, Wang X, et al., 2019, Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights from Clinical and Functional Neuroimaging Studies. Diabetes Care, 42(7): 1274–1283. https://www.doi.org/10.2337/dc18-2584
Gong H, Zheng F, Zuo Z, et al., 2020, Effect of DA-JC4 on Postoperative Neuroinflammatory Response in Aging Rats. Chinese Journal of Anesthesiology, 40(05): 588–591.
Ruze R, Xu Q, Liu G, et al., 2021, Central GLP-1 Contributes to Improved Cognitive Function and Brain Glucose Uptake After Duodenum-Jejunum Bypass on Obese and Diabetic Rats. Am J Physiol Endocrinol Metab, 321(3): e392–e409. https://www.doi.org/10.1152/ajpendo.00126.2021
Zhang Q, Jiang Y, Zhang Y, et al., 2022, GLP-1 Analog Alleviated Cognitive Dysfunction in Aged Rats Anaesthetized with Sevoflurane. Biomed Res Int, 2022: 9339824. https://www.doi.org/10.1155/2022/9339824
Sedky AA, Magdy Y, 2021, Reduction in TNF Alpha and Oxidative Stress by Liraglutide: Impact on Ketamine-Induced Cognitive Dysfunction and Hyperlocomotion in Rats. Life Sci, 278: 119523. https://www.doi.org/10.1016/j.lfs.2021.119523
Nizari S, Basalay M, Chapman P, et al., 2021, Glucagon-like Peptide-1 (GLP-1) Receptor Activation Dilates Cerebral Arterioles, Increases Cerebral Blood Flow, and Mediates Remote (Pre)Conditioning Neuroprotection Against Ischaemic Stroke. Basic Res Cardiol, 116(1): 32. https://www.doi.org/10.1007/s00395-021-00873-9
Zhang J, Yi T, Cheng S, et al., 2020, Glucagon-like Peptide-1 Receptor Agonist Exendin-4 Improves Neurological Outcomes by Attenuating TBI- Induced Inflammatory Responses and MAPK Activation in Rats. Int Immunopharmacol, 86: 106715. https://www.doi.org/10.1016/j.intimp.2020.106715
Benn M, Emanuelsson F, Tybjærg-Hansen A, et al., 2021, Impact of High Glucose Levels and Glucose Lowering on Risk of Ischaemic Stroke: a Mendelian Randomisation Study and Meta-Analysis. Diabetologia, 64(7): 1492–1503. https://www.doi.org/10.1007/s00125-021-05436-0
Trammell TS, Henderson NL, Madkour HS, et al., 2021, GLP-1R activation alters performance in cognitive tasks in a sex-dependent manner. Neurol Sci, 42(7): 2911–2919. https://www.doi.org/10.1007/s10072-020-04910-8
Seppa K, Jagomäe T, Kukker KG, et al., 2021, Liraglutide, 7,8-DHF and their co-treatment prevents loss of vision and cognitive decline in a Wolfram syndrome rat model. Sci Rep 11(1): 2275. https://www.doi.org/10.1038/s41598-021-81768-6
Sayed NH, Fathy N, Kortam MA, et al., 2020, Vildagliptin Attenuates Huntington’s Disease through Activation of GLP-1 Receptor/PI3K/Akt/BDNF Pathway in 3-Nitropropionic Acid Rat Model. Neurotherapeutics, 17(1): 252–268. https://www.doi.org/10.1007/s13311-019-00805-5
Safar MM, Shahin NN, Mohamed AF, et al., 2020, Suppression of BACE1 and Amyloidogenic/RAGE Axis by Sitagliptin Ameliorates PTZ Kindling-Induced Cognitive Deficits in Rats. Chem Biol Interact, 328: 109144. https://www.doi.org/10.1016/j.cbi.2020.109144
Mansur RB, Lee Y, Subramaniapillai M, et al., 2018, Cognitive Dysfunction and Metabolic Comorbidities in Mood Disorders: A Repurposing Opportunity for Glucagon-Like Peptide 1 Receptor Agonists?. Neuropharmacology, 136(Pt B): 335–342. https://www.doi.org/10.1016/j.neuropharm.2018.01.048
Flintoff J, Kesby JP, Siskind D, et al., 2021, Treating Cognitive Impairment in Schizophrenia with GLP-1RAs: An Overview of Their Therapeutic Potential. Expert Opin Investig Drugs, 30(8): 877–891. https://www.doi.org/10.1080/13543784.2021.1951702.
Hernandez NS, Weir VR, Ragnini K, et al., 2021, GLP-1 Receptor Signaling in the Laterodorsal Tegmental Nucleus Attenuates Cocaine Seeking by Activating GABAergic Circuits that Project to the VTA. Mol Psychiatry, 26(8): 4394–4408. https://www.doi.org/10.1038/s41380-020-00957-3
Jones S, Hyde A, Davidson TL, 2020, Reframing Appetitive Reinforcement Learning and Reward Valuation as Effects Mediated by Hippocampal-Dependent Behavioral Inhibition. Nutr Res, 79: 1–12. https://www.doi.org/10.1016/j.nutres.2020.05.001
Kong Q, Li Y, Yue J, et al., 2021, Reducing Alcohol and/or Cocaine-Induced Reward and Toxicity via an Epidermal Stem Cell-Based Gene Delivery Platform. Mol Psychiatry 26(9): 5266-5276. https://www.doi.org/10.1038/s41380-021-01043-y
Liu XY, Zhang N, Zhang SX, et al., 2021, Potential New Therapeutic Target for Alzheimer's Disease: Glucagon-Like Peptide-1. Eur J Neurosci, 54(10): 7749–7769. https://www.doi.org/10.1111/ejn.15502
Zhang H, Song B, Zhu W, et al., 2021, Glucagon-Like Peptide-1 Attenuated Carboxymethyl Lysine Induced Neuronal Apoptosis via Peroxisome Proliferation Activated Receptor-?. Aging (Albany NY) 13(14): 19013–19027. https://www.doi.org/10.18632/aging.203351
An J, Zhou Y, Zhang M, et al., 2019, Exenatide Alleviates Mitochondrial Dysfunction and Cognitive Impairment in the 5×FAD Mouse Model of Alzheimer’s Disease. Behav Brain Res 370: 111932. https://www.doi.org/10.1016/j.bbr.2019.111932
Eriksson O, Velikyan I, Haack T, et al., 2021, Imaging of the Glucagon Receptor in Subjects with Type 2 Diabetes. J Nucl Med, 62(6): 833–838. https://www.doi.org/10.2967/jnumed.118.213306
Zhou Y, Li Z, Cao X, et al., 2019, Exendin-4 Improves Behavioral Deficits via GLP-1/GLP-1R Signaling Following Partial Hepatectomy. Brain Res 1706: 116–124. https://www.doi.org/10.1016/j.brainres.2018.11.007
Hulst AH, Polderman JAW, Siegelaar SE, et al., 2021, Preoperative Considerations of New Long-Acting Glucagon-Like Peptide-1 Receptor Agonists in Diabetes Mellitus. Br J Anaesth, 126(3): 567–571. https://www.doi.org/10.1016/j.bja.2020.10.023