Background: Diabetes mellitus (DM), a metabolic disorder that leads to chronic hyperglycemia, is one of the topmost global public health concerns according to the International Diabetes Federation. Adropin is a peptide hormone that is primarily involved in energy homeostasis, but its involvement in other biological activities such as lowering hyperlipidemia, and diminishing insulin resistance has also been reported. In this study, we aimed to explore additional effects of adropin on oxidative stress, inflammation, and cell proliferation in an animal model of type 1 DM.
Methods: To achieve our aim, normal and diabetic Wistar rats were treated with adropin (2.1 μg/kg/day) for a period of 10 days. Pancreatic tissue samples were collected for histomorphological analysis and inflammation assay, while blood was collected for oxidative stress assay.
Results: Our results showed that diabetes induction stimulated cell proliferation in both exocrine and endocrine pancreas, and adropin dramatically attenuated this effect in pancreatic exocrine tissue, but not in the islet of Langerhans. In addition, adropin significantly increased glutathione reductase expression in pancreatic tissue, and augmented serum total glutathione in the diabetic rats compared to diabetic untreated rats.
Conclusion: Our study indicates the potential role of adropin in alleviating oxidative stress in DM.
| [1] |
Genitsaridi I, Salpea P, Salim A, et al. IDF diabetes atlas: global, regional and national diabetes prevalence estimates for 2024 and projections for 2050. 2025.
|
| [2] |
Antar SA, Ashour NA, Sharaky M, et al. Diabetes mellitus: classification, mediators, and complications; a gate to identify potential targets for the development of new effective treatments. Biomed Pharmacother. 2023; 168:115734.
|
| [3] |
Kumar KG, Trevaskis JL, Lam DD, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008; 8(6): 468-481.
|
| [4] |
Ali II, D'Souza C, Singh J, Adeghate E. Adropin's role in energy homeostasis and metabolic disorders. Int J Mol Sci. 2022; 23(15):8318.
|
| [5] |
Aydin S, Kuloglu T, Aydin S, et al. Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes. Mol Cell Biochem. 2013; 380(1–2): 73-81.
|
| [6] |
Chen L, Lu J, Hu J, Gong X. Unveiling the multifaceted role of adropin in various diseases (review). Int J Mol Med. 2024; 54(4):90.
|
| [7] |
Jasaszwili M, Billert M, Strowski MZ, Nowak KW, Skrzypski M. Adropin as a fat-burning hormone with multiple functions—review of a decade of research. Molecules. 2020; 25(3):549.
|
| [8] |
Ali II, D'Souza C, Tariq S, Adeghate EA. Adropin is expressed in pancreatic islet cells and reduces glucagon release in diabetes mellitus. Int J Mol Sci. 2024; 25(18):9824.
|
| [9] |
Zhao ZW, Ren YG, Liu J. Low serum adropin levels are associated with coronary slow flow phenomenon. Acta Cardiol Sin. 2018; 34(4): 307-312.
|
| [10] |
Soltani S, Kolahdouz-Mohammadi R, Aydin S, Yosaee S, Clark CCT, Abdollahi S. Circulating levels of adropin and overweight/obesity: a systematic review and meta-analysis of observational studies. Hormones (Athens). 2022; 21(1): 15-22.
|
| [11] |
Li S, Sun J, Hu W, et al. The association of serum and vitreous adropin concentrations with diabetic retinopathy. Ann Clin Biochem Int J Lab Med. 2019; 56(2): 253-258.
|
| [12] |
Hu W, Chen L. Association of serum adropin concentrations with diabetic nephropathy. Mediat Inflamm. 2016; 2016:6038261.
|
| [13] |
Sato K, Yamashita T, Shirai R, et al. Adropin contributes to anti-atherosclerosis by suppressing monocyte-endothelial cell adhesion and smooth muscle cell proliferation. Int J Mol Sci. 2018; 19(5): 1-16.
|
| [14] |
Liu Q, Zhang S, Liu G, et al. Adropin deficiency worsens TNBS-induced colitis. Int Immunopharmacol. 2023; 124:110891.
|
| [15] |
Gao F, Fang J, Chen F, et al. Enho mutations causing low adropin: a possible pathomechanism of MPO-ANCA associated lung injury. EBioMedicine. 2016; 9: 324-335.
|
| [16] |
Li B, Wang Z, He Y, et al. Adropin improves radiation-induced myocardial injury via VEGFR2/PI3K/Akt pathway. Oxidative Med Cell Longev. 2022; 2022:8230214.
|
| [17] |
Maurya S, Tripathi S, Arora T, Singh A. Adropin may regulate ovarian functions by improving antioxidant potential in adult mouse. J Steroid Biochem Mol Biol. 2024; 242:106524.
|
| [18] |
Lovren F, Pan Y, Quan A, et al. Adropin is a novel regulator of endothelial function. Circulation. 2010; 122(11 SUPPL. 1): 185-192.
|
| [19] |
Tuna BG, Atalay PB, Altunbek M, Kalkan BM, Dogan S. Effects of chronic and intermittent calorie restriction on adropin levels in breast cancer. Nutr Cancer. 2017; 69(7): 1003-1010.
|
| [20] |
Rao A, Herr DR. G protein-coupled receptor GPR19 regulates E-cadherin expression and invasion of breast cancer cells. Biochim Biophys Acta, Mol Cell Res. 2017; 1864(7): 1318-1327.
|
| [21] |
Hu J, Wu Q, Ding Q, Wu W, Li Q, Zheng Z. High level of Adropin promotes the progression of pancreatic ductal adenocarcinoma. Curr Cancer Drug Targets. 2023; 24(6): 629-641.
|
| [22] |
Akcilar R, Kocak FE, Simsek H, et al. Antidiabetic and hypolipidemic effects of adropinin streoptozotocin-induced type 2 diabetic rats. Bratisl Lek Listy. 2016; 116(2): 100-105.
|
| [23] |
Sun X, Kaufman PD. Ki-67: more than a proliferation marker. Chromosoma. 2018; 127(2): 175-186.
|
| [24] |
Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014; 383(9911): 69-82.
|
| [25] |
Yang W, Jiang Y, Wang Y, et al. Placental growth factor in beta cells plays an essential role in gestational beta-cell growth. BMJ Open Diabetes Res Care. 2020; 8(1):e000921.
|
| [26] |
Li J, Ying H, Cai G, Guo Q, Chen L. Pre-eclampsia-associated reduction in placental growth factor impaired Beta cell proliferation through PI3k Signalling. Cell Physiol Biochem. 2015; 36(1): 34-43.
|
| [27] |
Forbes S, Vig P, Poulsom R, Thomas H, Alison M. Pancreatic stem cells. 2002.
|
| [28] |
Jasaszwili M, Wojciechowicz T, Billert M, Strowski MZ, Nowak KW, Skrzypski M. Effects of adropin on proliferation and differentiation of 3T3-L1 cells and rat primary preadipocytes. Mol Cell Endocrinol. 2019; 496(July):110532.
|
| [29] |
Billert M, Jasaszwili M, Strowski M, Nowak KW, Skrzypski M. Adropin suppresses insulin expression and secretion in INS-1E cells and rat pancreatic islets. J Physiol Pharmacol. 2020; 71(1): 99-104.
|
| [30] |
Galicia-Garcia U, Benito-Vicente A, Jebari S, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 2020; 21(17):6275.
|
| [31] |
Ohiagu F, Ohiagu FO, Chikezie PC, Chikezie CM. Pathophysiology of diabetes mellitus complications: metabolic events and control. Biomed Res Ther. 2021; 8(3): 4243-4257.
|
| [32] |
Ammendola R, Cattaneo F, Ravera S, Black HS. A synopsis of the associations of oxidative stress, ROS, and antioxidants with diabetes mellitus. Antioxidants. 2022; 11(10):2003.
|
| [33] |
Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress—a concise review. Saudi Pharm J. 2016; 24(5): 547-553.
|
| [34] |
Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004; 134(3): 489-492.
|
| [35] |
Patel H, Chen J, Das KC, Kavdia M. Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC. Cardiovasc Diabetol. 2013; 12(1): 1-14.
|
| [36] |
Yu M, Wang D, Zhong D, Xie W, Luo J. Adropin carried by reactive oxygen species-responsive nanocapsules ameliorates renal lipid toxicity in diabetic mice. ACS Appl Mater Interfaces. 2022; 14(33): 37330-37344.
|
| [37] |
Rizk FH, el-Saka MH, Ibrahim RR, et al. Possible mitigating effect of adropin on lung injury in diabetic rats: targeting the role of rho a/rho-associated kinase pathway. Biofactors. 2023; 49: 928-939.
|
| [38] |
Tsalamandris S, Antonopoulos AS, Oikonomou E, et al. The role of inflammation in diabetes: current concepts and future perspectives. Eur Cardiol Rev. 2019; 14(1): 50-59.
|
| [39] |
Rohm TV, Meier DT, Olefsky JM, Donath MY. Inflammation in obesity, diabetes, and related disorders. Immunity. 2022; 55(1): 31-55.
|
| [40] |
Mastrandrea L, Yu J, Behrens T, et al. Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, double-blind study. Diabetes Care. 2009; 32(7): 1244-1249.
|
| [41] |
Larsen CM, Faulenbach M, Vaag A, Ehses JA, Donath MY, Mandrup-Poulsen T. Sustained effects of Interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care. 2009; 32(9): 1663-1668.
|
| [42] |
Chen S, Zeng K, Liu QC, et al. Adropin deficiency worsens HFD-induced metabolic defects. Cell Death Dis. 2017; 8(8):e3008.
|
| [43] |
Chen X, Xue H, Fang W, et al. Adropin protects against liver injury in nonalcoholic steatohepatitis via the Nrf2 mediated antioxidant capacity. Redox Biol. 2019; 21:101068.
|
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2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.
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