GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2021 Sep 9

PMID 34497589

Citations 103

Authors

Xin Zhao

Minghe Wang

Zhitong Wen

Zhihong Lu

Lijuan Cui

Chao Fu

Huan Xue

Yunfeng Liu

Yi Zhang

Affiliations

Soon will be listed here.

Abstract

Glucagon like peptide-1 (GLP-1) is an incretin secretory molecule. GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes (T2DM) due to their attributes such as body weight loss, protection of islet β cells, promotion of islet β cell proliferation and minimal side effects. Studies have found that GLP-1R is widely distributed on pancreatic and other tissues and has multiple biological effects, such as reducing neuroinflammation, promoting nerve growth, improving heart function, suppressing appetite, delaying gastric emptying, regulating blood lipid metabolism and reducing fat deposition. Moreover, GLP-1RAs have neuroprotective, anti-infectious, cardiovascular protective, and metabolic regulatory effects, exhibiting good application prospects. Growing attention has been paid to the relationship between GLP-1RAs and tumorigenesis, development and prognosis in patient with T2DM. Here, we reviewed the therapeutic effects and possible mechanisms of action of GLP-1RAs in the nervous, cardiovascular, and endocrine systems and their correlation with metabolism, tumours and other diseases.

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References

Gerstein H, Hart R, Colhoun H, Diaz R, Lakshmanan M, Botros F . The effect of dulaglutide on stroke: an exploratory analysis of the REWIND trial. Lancet Diabetes Endocrinol. 2020; 8(2):106-114. DOI: 10.1016/S2213-8587(19)30423-1. View

Nassar N, Al-Shorbagy M, Arab H, Abdallah D . Saxagliptin: a novel antiparkinsonian approach. Neuropharmacology. 2014; 89:308-17. DOI: 10.1016/j.neuropharm.2014.10.007. View

Roth G, Forouzanfar M, Moran A, Barber R, Nguyen G, Feigin V . Demographic and epidemiologic drivers of global cardiovascular mortality. N Engl J Med. 2015; 372(14):1333-41. PMC: 4482354. DOI: 10.1056/NEJMoa1406656. View

Holscher C . Central effects of GLP-1: new opportunities for treatments of neurodegenerative diseases. J Endocrinol. 2013; 221(1):T31-41. DOI: 10.1530/JOE-13-0221. View

Papaetis G, Filippou P, Constantinidou K, Stylianou C . Liraglutide: New Perspectives for the Treatment of Polycystic Ovary Syndrome. Clin Drug Investig. 2020; 40(8):695-713. DOI: 10.1007/s40261-020-00942-2. View

Nomiyama T, Kawanami T, Irie S, Hamaguchi Y, Terawaki Y, Murase K . Exendin-4, a GLP-1 receptor agonist, attenuates prostate cancer growth. Diabetes. 2014; 63(11):3891-905. DOI: 10.2337/db13-1169. View

Tsilidis K, Kasimis J, Lopez D, Ntzani E, Ioannidis J . Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ. 2015; 350:g7607. DOI: 10.1136/bmj.g7607. View

Bartels A, Willemsen A, Doorduin J, de Vries E, Dierckx R, Leenders K . [11C]-PK11195 PET: quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson's disease?. Parkinsonism Relat Disord. 2009; 16(1):57-9. DOI: 10.1016/j.parkreldis.2009.05.005. View

Meier J, Nauck M, Kranz D, Holst J, Deacon C, Gaeckler D . Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes. 2004; 53(3):654-62. DOI: 10.2337/diabetes.53.3.654. View

10.

Elkind-Hirsch K, Marrioneaux O, Bhushan M, Vernor D, Bhushan R . Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008; 93(7):2670-8. DOI: 10.1210/jc.2008-0115. View

11.

Ricciarelli R, Fedele E . The Amyloid Cascade Hypothesis in Alzheimer's Disease: It's Time to Change Our Mind. Curr Neuropharmacol. 2017; 15(6):926-935. PMC: 5652035. DOI: 10.2174/1570159X15666170116143743. View

12.

Bell G, Laybourn P, Najarian R . Exon duplication and divergence in the human preproglucagon gene. Nature. 1983; 304(5924):368-71. DOI: 10.1038/304368a0. View

13.

Suh S, Kim K . Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment. Diabetes Metab J. 2020; 43(6):733-743. PMC: 6943263. DOI: 10.4093/dmj.2019.0177. View

14.

Pereira S, Park E, Moore J, Faubert B, Breen D, Oprescu A . Resveratrol prevents insulin resistance caused by short-term elevation of free fatty acids in vivo. Appl Physiol Nutr Metab. 2015; 40(11):1129-36. DOI: 10.1139/apnm-2015-0075. View

15.

Sanyal A . Past, present and future perspectives in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2019; 16(6):377-386. DOI: 10.1038/s41575-019-0144-8. View

16.

Zhao H, Wang L, Wei R, Xiu D, Tao M, Ke J . Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway. Diabetes Obes Metab. 2014; 16(9):850-60. DOI: 10.1111/dom.12291. View

17.

Yildirim Simsir I, Soyaltin U, Cetinkalp S . Glucagon like peptide-1 (GLP-1) likes Alzheimer's disease. Diabetes Metab Syndr. 2018; 12(3):469-475. DOI: 10.1016/j.dsx.2018.03.002. View

18.

Ashburn M, Staats P . Management of chronic pain. Lancet. 1999; 353(9167):1865-9. DOI: 10.1016/S0140-6736(99)04088-X. View

19.

Almutairi M, Al Batran R, Ussher J . Glucagon-like peptide-1 receptor action in the vasculature. Peptides. 2018; 111:26-32. DOI: 10.1016/j.peptides.2018.09.002. View

20.

Liu H, Zhan Y, Luo G, Zou L, Li Y, Lu H . Liraglutide and Insulin Have Contrary Effects on Adipogenesis of Human Adipose-Derived Stem Cells via Wnt Pathway. Diabetes Metab Syndr Obes. 2020; 13:3075-3087. PMC: 7478378. DOI: 10.2147/DMSO.S253097. View