View Point. Glucagon Like Peptide-1 Levels and Its Variability


Authors: Galal Elkilany, Ram B Singh, Osama Elmarghi, Jan Fedacko, Narsingh Verma, Anuj Maheshwari, Saibal Chakravorty, and Germaine Cornelissen
Page Range: 109-115
Published in: World Heart Journal, 14#2 (2022)
ISSN: 1556-4002

ISBN: N/A Category:

Table of Contents


Two gut hormones, glucagon like peptide GLP)-1 and glucose-dependent insulin-tropic polypeptide (GIP, gastric inhibitory polypeptide), act as incretins. GLP-1 is released by the direct actions of luminal food contents on the L cells in the distal jejunum and proximal ileum. New evidence suggests an additional mechanism via the gut-brain axis, involving lower- as well as upper-gut signals, which may activate GLP-1 release even before the luminal nutrients have reached the proximities of L cells. Ethnic differences in GLP-1 concentrations may be due to diet quality in terms of monosaccharides, glucose, fructose, polysaccharides, proteins, and fatty acids, among others. These nutrients may alter GLP-1 receptor responses to food intake and fasting. Novel glucose-lowering agents, the dipeptidyl-peptidase-4 (DPP-4) inhibitors, work by preventing the inactivation of incretin hormones GLP-1 and GIP. Increased degradation of GLP-1 via DPP-4 enzymes is hence an additional mechanism for altering GLP-1 concentrations. DPP-4 inhibitors, used to treat diabetes mellitus type 2, inhibit DPP-4 activity in peripheral plasma, which prevents the inactivation of GLP-1 in the peripheral circulation. The presence of GLP-1 receptors in various organs (heart, brain, liver, pancreas, kidney, muscle and bone) makes their activation possible, thereby offering protection to the related organs.

Keywords: Incretins, glyptins, gut hormones, glucose metabolism


[1] Müller TD, Finan B, Bloom SR, D’Alessio D, Drucker DJ, Flatt PR, Fritsche A, Gribble F, Grill HJ, Habener JF, Holst JJ, Langhans W, Meier JJ, Nauck MA, Perez-Tilve D, Pocai A, Reimann F, Sandoval DA, Schwartz TW, Seeley RJ, Stemmer K, Tang-Christensen M, Woods SC, DiMarchi RD, Tschöp MH. Glucagon-like peptide 1 (GLP-1). Mol Metab 2019; 30: 72-130. 09.010.
[2] Yamaoka-Tojo M, Tojo T, Takahira N, Matsunaga A, Aoyama N, Masuda T, Izumi T. Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease. Cardiovasc Diabetol 2010; 9: 17. doi:10.1186/1475-2840-9-17.
[3] Bodnaruc AM, Prud’homme D, Blanchet R, Giroux I. Nutritional modulation of endogenous glucagon-like peptide-1 secretion: a review. Nutr Metab (Lond) 2016; 13: 92.
[4] Sleddering MA, Bakker LEH, Jansen LGM, Jaget IM. Higher insulin and glucagon-like peptide-1 (GLP-1) levels in healthy, young South Asians as compared to Caucasians during an oral glucose tolerance test. Metabolism 2014; 63 (2): 226-232. doi: 10.1016/j.metabol.2013.10.008.
[5] Singh AK. Glucagon-like peptide 1 and dysglycemia: Conflict in incretin science. Indian J Endocrinol Metab 2015; 19 (1): 182-187.
[6] Velasquez-Mieyer PA, Cowan PA, Umpierrez GE, Lustig RH, Cashion AK, Burghen GA. Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects. Int J Obes Relat Metab Disord 2003; 27 (11): 1359-1364. doi: 10.1038/sj.ijo.0802415.
[7] Seino Y, Fukushima M, Yabe D: GIP and GLP-1, the two incretin hormones: similarities and differences. J Diabetes Invest 2010, 1: 8-23.
[8] Lastya A, Saraswati MR, Suastika K. The low level of glucagon-like peptide-1 (glp-1) is a risk factor of type 2 diabetes mellitus. BMC Res Notes 2014; 7: 849.
[9] Holst JJ: The physiology of glucagon-like peptide 1. Physiological Reviews 2007; 87 (4): 1409-1439. doi: 10.1152/physrev.00034.2006.
[10] Velásquez-Mieyer PA, Cowan PA, Pérez-Faustinelli S, Nieto-Martínez R, Villegas-Barreto C, Tolley EA, Lustig RH, Alpert BS. Racial disparity in glucagon-like peptide 1 and inflammation markers among severely obese adolescents. Diabetes Care 2008; 31: 770-775. 10.2337/dc07-1525.
[11] Yabe D: Little enhancement of meal-induced glucagon-like peptide 1 secretion in Japanese: comparison of type 2 diabetes patients and healthy controls. J Diabetes Invest 2010, 1: 56-59. 10.1111/j.2040-1124.2010.00010.x.
[12] Zhang F, Tang X, Cao H, Lü Q, Li N, Liu Y, Zhang X, Zhang Y, Cao M, Wan J, An Z, Tong N: Impaired secretion of total glucagon-like peptide-1 in people with impaired fasting glucose combined impaired glucose tolerance. Int J Med Sci 2012, 9: 574-581. 10.7150/ijms.4128.
[13] Legakis IN, Tzioras C, Phenekos C: Decreased glucagon-like peptide 1 fasting levels in type 2 diabetes. Diabetes Care 2003; 26: 252. 10.2337/diacare.26.1.252.
[14] Freeman JS: Role of the incretin pathway in the pathogenesis of type 2 diabetes mellitus. Cleve Clin J Med 2009; 76 (Suppl 5): S12-S19.
[15] Nauck MA, Vardarli I, Deacon CF, Holst JJ, Meier JJ: Secretion of glucagon-like peptide-1 (glp-1) in type 2 diabetes: what is up, what is down? Diabetologia 2011; 54: 10-18. 10.1007/s00125-010-1896-4.
[16] Vilsbøll T, Krarup T, Sonne J, Madsbad S, Vølund A, Juul AG, Holst JJ. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 2003; 88: 2706-2713. 10.1210/jc.2002-021873.
[17] Vilsbøll T, Agerso H, Krarup T, Holst JJ. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 2003; 88: 220-224. 10.1210/jc.2002-021053.
[18] Calanna S, Christensen M, Holst JJ, Laferrere B, Gluud LL, Vilsbøll T, Knop FK. Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: Systematic review and meta-analyses of clinical studies. Diabetologia 2013; 56: 965–972.
[19] Singh AK. Incretin response in Asian type 2 diabetes: Are Indians different? Indian J Endocrinol Metab 2015; 19 (1): 30-38. doi:10.4103/2230-8210.146861.
[20] Toft-Nielsen MB, Damholt MB, Madsbad S, Hilsted LM, Hughes TE, Michelsen BK, Holst JJ. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001; 86: 3717–3723.
[21] Biancolin AD, Martchenko A, Mitova E, Gurges P, Michalchyshyn E, Chalmers JA, Doria A, Mychaleckyj JC, Adriaenssens AE, Reimann F, Gribble FM, Gil-Lozano M, Cox BJ, Brubaker PL. The core clock gene, Bmal1, and its downstream target, the SNARE regulatory protein secretagogin, are necessary for circadian secretion of glucagon-like peptide-1. Mol Metab 2020; 31: 124-137.
[22] Gil-Lozano M, Mingomataj EL, Wu WK, Ridout SA, Brubaker PL. Circadian secretion of the intestinal hormone GLP-1 by the rodent L cell. Diabete. 2014; 63 (11): 3674–3685.
[23] Gil-Lozano M, Hunter PM, Behan L-A, Gladanac B, Casper RF, Brubaker PL. Short-term sleep deprivation with nocturnal light exposure alters time-dependent glucagon-like peptide-1 and insulin secretion in male volunteers. Am J Physiol: Endocrinol Metab 2015; 310 (1): 41–50.
[24] Lindgren O, Mari A, Deacon CF, Carr RD, Winzell MS, Vikman J. Differential islet and incretin hormone responses in morning versus afternoon after standardized meal in healthy men. J Clin Endocrinol Metab 2009; 94 (8): 2887–2892.
[25] Maersk M, Belza A, Holst JJ, Fenger-Gron M, Pedersen SB, Astrup A. Satiety scores and satiety hormone response after sucrose-sweetened soft drink compared with isocaloric semi-skimmed milk and with non-caloric soft drink: a controlled trial. Eur J Clin Nutr 2012; 66: 523–529.
[26] Liu AG, Puyau RS, Han H, Johnson WD, Greenway FL, Dhurandhar NV. The effect of an egg breakfast on satiety in children and adolescents: A randomized crossover trial. J Am Coll Nutr 2015; 34: 1–6.
[27] Thomsen C., Rasmussen O., Lousen T., Holst J. J., Fenselau S., Schrezenmeir J. Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects. Am J Clin Nutr 1999; 69: 1135–1143.
[28] Freeland KR, Wilson C, Wolever TMS. Adaptation of colonic fermentation and glucagon-like peptide-1 secretion with increased wheat fibre intake for 1 year in hyperinsulinaemic human subjects. Br J Nutr 2010; 103:82–90.
[29] Nilsson AC, Johansson-Boll EV, Björck IME. Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study in healthy middle-aged subjects. Br J Nutr 2015; 114: 899–907.
[30] Reis CEG, Ribeiro DN, Costa NMB, Bressan J, Alfenas RCG, Mattes RD. Acute and second-meal effects of peanuts on glycaemic response and appetite in obese women with high type 2 diabetes risk: a randomised cross-over clinical trial. Br J Nutr 2013; 109: 2015–2023.
[31] Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Nat Acad Sci USA 2007; 104: 15069–15074.
[32] Husted AS, Trauelsen M, Rudenko O, Hjorth SA, Schwartz TW. GPCR-mediated signaling of metabolites. Cell Metab 2017; 25: 777–796.
[33] Kang YM, Cho YK, Lee J, Lee SE, Lee WJ, Park JY, Kim YJ, Jung CH, Nauck MA. Asian subpopulations may exhibit greater cardiovascular benefit from long-acting glucagon-like peptide 1 receptor agonists: a meta-analysis of cardiovascular outcome trials. Diabetes Metab J 2019; 43 (4): 410-421. doi:10.4093/dmj.2018.0070.
[34] Tan MMT, Khoo B. Tirzepatide and the new era of twincretins for diabetes. Lancet 2021; 398: 95-97.

Publish with Nova Science Publishers

We publish over 800 titles annually by leading researchers from around the world. Submit a Book Proposal Now!