Abstract
Background
The current study was designed to highlight the effects of heterologous platelet-rich plasma (PRP) on deteriorated hepatic tissues and impaired glucose metabolism of alloxan-induced diabetic mice.
Methods
30 male mice were divided into a control (CG), PRP (PG), diabetic (DG), and two treated groups (T1G and T2G). PG was given PRP treatment (0.5 ml/kg body weight) twice a week for four weeks. DG, T1G and T2G were given alloxan (150 mg/kg) to induce diabetes. After confirmation, PRP treatment was given to T1G and T2G for two and four weeks respectively while DG was left untreated. Upon completion of the said experimental period, liver samples were taken for histological and gene expression analyses.
Results
The study found that the liver tissue of the DG group showed signs of damage, including hepatocyte ballooning, sinusoid dilatation, and collagen deposition. However, these changes were significantly reduced in both T1G and T2G groups. The expression of several genes related to liver function was also affected, with upregulation of Fbp1 and Pklr, and downregulation of Pck1 in the DG group. PRP treatment restored Fbp1 expression and also increased the expression of glycolytic pathway genes Hk1 and Gck, as well as Wnt signalling pathway genes Wnt2, Wnt4, and Wnt9a in both treated groups.
Conclusion
Current study revealed that heterologous PRP may partly alleviate high glucose levels in diabetics possibly by mediating glucose metabolism via inhibition of Wnt signalling pathway.
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Abbreviations
- DG:
-
Diabetic group
- DM:
-
Diabetes Mellitus
- ECM:
-
Extracellular matrix
- GFs:
-
Growth factors
- HSCs:
-
Hepatic stellate cells
- PRP:
-
Platelet-rich plasma
- T1G:
-
Treated group 1
- T2G:
-
Treated group 2
References
Andreadi A, Bellia A, Di Daniele N, Meloni M, Lauro R, Della-Morte D, Lauro D (2022) The molecular link between oxidative stress, insulin resistance, and type 2 diabetes: a target for new therapies against cardiovascular diseases. Curr Opin Pharmacol 62:85–96. https://doi.org/10.1016/j.coph.2021.11.010
Rebelos E, Iozzo P, Guzzardi MA, Brunetto MR, Bonino F (2021) Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease. World J Gastroenterol 27(30):4999. https://doi.org/10.3748%2Fwjg.v27.i30.4999
Oberhauser L, Maechler P (2022) Lipid-induced adaptations of the pancreatic beta-cell to glucotoxic conditions sustain insulin secretion. Int J Mol Sci 23(1):324. https://doi.org/10.3390/ijms23010324
Tong X, Liu S, Stein R, Imai Y (2022) Lipid droplets’ role in the regulation of β-Cell function and β-Cell demise in type 2 diabetes. Endocrinology 163(3):bqac007. https://doi.org/10.1210/endocr/bqac007
Scott SN, Anderson L, Morton JP, Wagenmakers AJ, Riddell MC (2019) Carbohydrate restriction in type 1 diabetes: a realistic therapy for improved glycaemic control and athletic performance. Nutrients 11:1022. https://doi.org/10.3390/nu11051022
Khin PP, Lee JH, Jun HS (2023) Pancreatic Beta-cell dysfunction in type 2 diabetes. Eur J Inflamm. https://doi.org/10.1177/1721727X231154152. .21:1721727X231154152
Jiang S, Young JL, Wang K, Qian Y, Cai L (2020) Diabetic–induced alterations in hepatic glucose and lipid metabolism: the role of type 1 and type 2 diabetes mellitus. Mol Med Rep 22:603–611. https://doi.org/10.3892/mmr.2020.11175
Murakami S, Funahashi K, Tamagawa N, Ning M, Ito T (2022) Taurine ameliorates streptozotocin-induced diabetes by modulating hepatic glucose metabolism and oxidative stress in mice. Metabolites 12(6):524. https://doi.org/10.3390/metabo12060524
Zhang F, Xu X, Zhang Y, Zhou B, He Z, Zhai Q (2013) Gene expression profile analysis of type 2 diabetic mouse liver. PLoS ONE 8:e57766. https://doi.org/10.1371/journal.pone.0057766
Ashrafizadeh M, Ahmadi Z, Mohamamdinejad R, Yaribeygi H, Serban MC, Orafai MH, Sahebkar A (2020) Curcumin therapeutic modulation of the wnt signaling pathway. Curr Pharm Biotechnol 21:1006–1015. https://doi.org/10.2174/1389201021666200305115101
Nie X, Wei X, Ma H, Fan L, Chen WD (2021) The complex role of wnt ligands in type 2 diabetes mellitus and related complications. J Cell Mol Med 25:6479–6495. https://doi.org/10.1111/jcmm.16663
Sills ES, Wood SH (2019) Autologous activated platelet-rich plasma injection into adult human ovary tissue: molecular mechanism, analysis, and discussion of reproductive response. Biosci Rep. https://doi.org/10.1042/BSR20190805
Everts P, Onishi K, Jayaram P, Lana JF, Mautner K (2020) Platelet-rich plasma: new performance understandings and therapeutic considerations in 2020. Int J Mol Sci 21:7794. https://doi.org/10.3390/ijms21207794
Yu H, Zhou Z, Yu B, Sun T, Tang Q, Jia Y (2022) The efficacy of platelet-rich plasma applicated in spinal fusion surgery: a meta-analysis. Front Surg 9:924753. https://doi.org/10.3389/fsurg.2022.924753
Imam SS, Al-Abbasi FA, Hosawi S, Afzal M, Nadeem MS, Ghoneim MM, Alshehri S, Alzarea SI, Alquraini A, Gupta G, Kazmi I (2022) Role of platelet rich plasma mediated repair and regeneration of cell in early stage of cardiac injury. Regen Ther 19:144–153. https://doi.org/10.1016/j.reth.2022.01.006
Gentile P, Garcovich S (2021) Systematic review: adipose-derived mesenchymal stem cells, platelet-rich plasma and biomaterials as new regenerative strategies in chronic skin wounds and soft tissue defects. Int J Mol Sci 22:1538. https://doi.org/10.3390/ijms22041538
Lana JF, Huber SC, Purita J, Tambeli CH, Santos GS, Paulus C, Annichino-Bizzacchi JM (2019) Leukocyte-rich PRP versus leukocyte-poor PRP-The role of monocyte/macrophage function in the healing cascade. J Clin Orthop Trauma 10:S7–12. https://doi.org/10.1016/j.jcot.2019.05.008
El-Tahawy NF, Rifaai RA, Saber EA, Saied SR, Ibrahim RA (2017) Effect of platelet rich plasma (prp) injection on the endocrine pancreas of the experimentally induced diabetes in male albino rats: a histological and immunohistochemical study. J Diabetes Metab 8(730):2. https://doi.org/10.4172/2155-6156.1000730
Abbasi MH, Fatima S, Khawar MB, Jahan S, Sheikh N (2018) An In Vivo Study on intoxicating effects of Nerium oleander Water based extract on multiorgans of Wistar rat. Can J Gastroenterol Hepatol. https://doi.org/10.1155/2018/4739637
Dubey S, Yadav C, Bajpeyee A, Singh MP (2020) Effect of Pleurotus fossulatus aqueous extract on biochemical properties of liver and kidney in streptozotocin-induced diabetic rat. Diabetes Metab Syndr Obes 13:3035–3046. https://doi.org/10.2147%2FDMSO.S265798
Nemati M, Karbalaei N, Mokarram P, Dehghani F (2020) Effects of platelet-rich plasma on the pancreatic islet survival and function, islet transplantation outcome and pancreatic pdx1 and insulin gene expression in streptozotocin-induced diabetic rats. Growth Factors 38:137–151. https://doi.org/10.1080/08977194.2021.1881502
Zarin M, Karbalaei N, Keshtgar S, Nemati M (2019) Platelet-rich plasma improves impaired glucose hemostasis, disrupted insulin secretion, and pancreatic oxidative stress in streptozotocin-induced diabetic rat. Growth Factors 37:226–237. https://doi.org/10.1080/08977194.2020.1735382
Mistry J, Biswas M, Sarkar S, Ghosh S (2023) Antidiabetic activity of mango peel extract and mangiferin in alloxan-induced diabetic rats. Futur J Pharm Sci 9(1):1–3. https://doi.org/10.1186/s43094-023-00472-6
El-Shawi OE, El-Nashar HA, Abd El-Rahman SS, Eldahshan OA, Singab AN (2022) Protective effect of Acrocarpus fraxinifolius extract against hepatic fibrosis induced by gamma irradiation and carbon tetrachloride in albino rats. Int J Radiat Biol 22:1–1. https://doi.org/10.1080/09553002.2022.2087926
Plaz Torres MC, Jaffe A, Perry R, Marabotto E, Strazzabosco M, Giannini EG (2022) Diabetes medications and risk of HCC. Hepatology 76(6):1880–1897. https://doi.org/10.1002/hep.32439
Rosenblatt R, Atteberry P, Tafesh Z et al (2021) Uncontrolled diabetes mellitus increases risk of infection in patients with advanced cirrhosis. Dig Liver Dis 53:445–451. https://doi.org/10.1016/j.dld.2020.10.022
Faccioli LA, Dias ML, Paranhos BA, dos Santos Goldenberg RC (2022) Liver cirrhosis: an overview of experimental models in rodents. Life Sci 5:120615. https://doi.org/10.1016/j.lfs.2022.120615
Hatting M, Tavares CD, Sharabi K, Rines AK, Puigserver P (2018) Insulin regulation of gluconeogenesis. Ann N Y Acad Sci 1411:21–35. https://doi.org/10.1111/nyas.13435
Asghar A, Sharif A, Awan SJ, Akhtar B, Akhtar MF, Ali S (2023) Ficus johannis Boiss. Leaves ethanolic extract ameliorate streptozotocin-induced diabetes in rats by upregulating the expressions of GCK, GLUT4, and IGF and downregulating G6P. Environ Sci Pollut Res 30(17):49108–49124. https://doi.org/10.1007/s11356-023-25765-4
Li M, Dang Y, Li Q et al (2019) Berberine alleviates hyperglycemia by targeting hepatic glucokinase in diabetic db/db mice. Sci Rep 9:1–12. https://doi.org/10.1038/s41598-019-48075-7
Moreno-Navarrete JM, Fernández-Real JM (2017) Adipocyte differentiation Adipose tissue biology. Springer, Cham, pp 69–90. https://doi.org/10.1007/978-3-319-52031-5_3
Maschio DA, Matheus VA, Collares-Buzato CB (2019) Islet cells are the source of wnts that can induce beta‐cell proliferation in vitro. J Cell Physiol 234(11):19852–19865. https://doi.org/10.1002/jcp.28584
Acknowledgements
The authors are highly thankful to the Vice-Chancellor, University of the Punjab, Lahore, Pakistan for his support for accomplishing this research work. Furthermore, it stated that this manuscript has been submitted to a preprint platform having DOI: https://doi.org/10.21203/rs.3.rs-1910439/v1 and licensed under a Creative Commons Attribution 4.0 International License.
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AA and AF performed the major part of this research work, did statistical analysis, interpretation of results, and initial draft. MBK revised the figures, improved the initial draft, and helped in lab work. TA, RM and TS, HAA and MA helped in lab work. MHA and NS conceived the idea, supervised the work, revised, modified, and approved the final draft.
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Arif, A., Farooq, A., Abbasi, M.H. et al. Effect of heterologous platelet-rich plasma on liver and modulation of glucose metabolism and Wnt signalling pathways in diabetic mice. Mol Biol Rep 50, 7145–7154 (2023). https://doi.org/10.1007/s11033-023-08600-4
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DOI: https://doi.org/10.1007/s11033-023-08600-4