Impact of Glyphosate on the Development of Type-2 Diabetes in Adipose Tissue: Role of Insulin-Like Growth Factor 1 and Tumor Necrosis Factor Alpha Expression

Download Article

DOI: 10.21522/TIJPH.2013.SE.24.01.Art023

Authors : Vishnu Priya Veeraraghavan, Gayathri R, Kavitha S, J. Selvaraj, Medha Rajiv Ranjan


Glyphosate, a commonly used herbicide in agricultural and residential settings, has sparked concerns regarding its potential health impacts. Despite numerous studies exploring potential associations between glyphosate exposure and diabetes, the precise mechanisms remain unclear. Tumor Necrosis Factor-alpha (TNF-α) and Insulin-Like Growth Factor 1 (IGF-1) are implicated in insulin resistance and pancreatic beta cell dysfunction, playing crucial roles in diabetes pathogenesis, especially Type 2 diabetes. This study aimed to assess the effect of glyphosate on TNF-α and IGF-1 expression in male Wistar rats. The results revealed a dose-dependent increase (p<0.05) in TNF-α and IGF-1 expression in adipose tissue following glyphosate exposure compared to the control group. These findings suggest that glyphosate exposure may contribute to the development of diabetes by altering the expression of IGF-1 and TNF-α.


[1] Gardner, J. G., Nelson, G. C., 2008, Herbicides, glyphosate resistance and acute mammalian toxicity: simulating an environmental effect of glyphosate-resistant weeds in the USA. Pest Management Science, 64(4), 470–478.

[2] de Castilhos Ghisi, N., Zuanazzi, N. R., Fabrin, T. M. C., Oliveira, E. C. 2020, Glyphosate and its toxicology: A scientometric review. The Science of the Total Environment, 733, 139359.

[3] Clair, E., Mesnage, R., Travert, C., Séralini, G. É., 2012, A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decreases at lower levels. Toxicology in vitro : an international journal published in association with BIBRA, 26(2), 269–279.

[4] Gętek-Paszek, M., Całyniuk, B., Ganczarek-Gamrot, A., Janion, K., Muc-Wierzgoń, M., Nowakowska-Zajdel, E., 2020, Recommendations of the Polish Society of Diabetology and the Lifestyle of Patients with Type 2 Diabetes Mellitus: An Own Research. Healthcare (Basel, Switzerland), 8(4), 504.

[5] Wild S. H., 2011, Diabetes, treatments for diabetes and their effect on cancer incidence and mortality: attempts to disentangle the web of associations. Diabetologia, 54(7), 1589–1592.

[6] Thomas, A. G., Holly, J. M., Taylor, F., Miller, V., 1993, Insulin like growth factor-I, insulin like growth factor binding protein-1, and insulin in childhood Crohn's disease. Gut, 34(7), 944–947.

[7] Parameswaran, N., Patial, S., 2010, Tumor necrosis factor-α signaling in macrophages. Critical reviews in eukaryotic gene expression, 20(2), 87–103.

[8] Wu, F., Zhu, J., Li, G., Wang, J., Veeraraghavan, V. P., Krishna Mohan, S., & Zhang, Q. (2019). Biologically Synthesized Green Gold Nanoparticles from Siberian Ginseng Induce Growth-Inhibitory Effect on Melanoma Cells (B16). Artificial Cells, Nanomedicine, And Biotechnology, 47(1), 3297–3305.

[9] Chen, F., Tang, Y., Sun, Y., Veeraraghavan, V. P., Mohan, S. K., Cui, C., 2019, 6-shogaol, an active constiuents of ginger prevents UVB radiation mediated inflammation and oxidative stress through modulating NrF2 signaling in human epidermal keratinocytes (HaCaT cells). Journal of Photochemistry and Photobiology. B, Biology, 197, 111518.

[10] Li, Z., Veeraraghavan, V. P., Mohan, S. K., Bolla, S. R., Lakshmanan, H., Kumaran, S., Aruni, W., Aladresi, A. A. M., Shair, O. H. M., Alharbi, S. A., Chinnathambi, A., 2020, Apoptotic induction and anti-metastatic activity of eugenol encapsulated chitosan nanopolymer on rat glioma C6 cells via alleviating the MMP signaling pathway. Journal of Photochemistry and Photobiology. B, Biology, 203, 111773.

[11] Babu, S., Jayaraman, S., 2020, An update on β-sitosterol: A potential herbal nutraceutical for diabetic management. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 131, 110702.

[12] Malaikolundhan, H., Mookkan, G., Krishnamoorthi, G., Matheswaran, N., Alsawalha, M., Veeraraghavan, V. P., Krishna Mohan, S., Di, A., 2020, Anticarcinogenic effect of gold nanoparticles synthesized from Albizia lebbeck on HCT-116 colon cancer cell lines. Artificial cells, Nanomedicine, and Biotechnology, 48(1), 1206–1213.

[13] Han, X., Jiang, X., Guo, L., Wang, Y., Veeraraghavan, V. P., Krishna Mohan, S., Wang, Z., Cao, D.2019, Anticarcinogenic potential of gold nanoparticles synthesized from Trichosanthes kirilowii in colon cancer cells through the induction of apoptotic pathway. Artificial Cells, Nanomedicine, And Biotechnology, 47(1), 3577–3584.

[14] Gothai, S., Muniandy, K., Gnanaraj, C., Ibrahim, I. A. A., Shahzad, N., Al-Ghamdi, S. S., Ayoub, N., Veeraraghavan, V. P., Kumar, S. S., Esa, N. M., Arulselvan, P., 2018, Pharmacological insights into antioxidants against colorectal cancer: A detailed review of the possible mechanisms. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 107, 1514–1522.

[15] Veeraraghavan, V.P., Hussain, S., Balakrishna, J.P., Dhawale, L., Kullappan, M., Ambrose, J.M, et al., 2021, A Comprehensive and Critical Review on Ethnopharmacological Importance of Desert Truffles: Terfezia claveryi, Terfezia boudieri, and Tirmania nivea, Food Reviews International, 1–20.

[16] Sathya, S., Ragul, V., Veeraraghavan, V.P., Singh, L., Niyas Ahamed, M.I., 2020, An in vitro study on hexavalent chromium [Cr(VI)] remediation using iron oxide nanoparticles-based beads, Environmental Nanotechnology, Monitoring & Management, 2020, 14, 100333.

[17] Yang, Z., Pu, M., Dong, X., Ji, F., Priya Veeraraghavan, V., Yang, H., 2020, Piperine loaded zinc oxide nanocomposite inhibits the PI3K/AKT/mTOR signaling pathway via attenuating the development of gastric carcinoma: In vitroandin vivostudies. Arabian Journal of Chemistry, 13(5), 5501–16.

[18] Rajendran, P., Alzahrani, A.M., Rengarajan, T., Veeraraghavan, V.P., Krishna Mohan, S., 2020, Consumption of reused vegetable oil intensifies BRCA1 mutations, Crit Rev Food Sci Nutr, 27,1–8.

[19] Barma, M.D., Muthupandiyan, I., Samuel, S.R., Amaechi, B.T., 2021, Inhibition of Streptococcus mutans, antioxidant property and cytotoxicity of novel nano-zinc oxide varnish. Arch Oral Biol, 126, 105132.

[20] Samuel, S.R., Can 5-year-olds sensibly self-report the impact of developmental enamel defects on their quality of life? Int J Paediatr Dent, 31(2), 285–6.

[21] Samuel SR, Kuduruthullah S, Khair AMB, Shayeb MA, Elkaseh A, Varma SR. Dental pain, parental SARS-CoV-2 fear and distress on quality of life of 2- to 6-year-old children during COVID-19. Int J Paediatr Dent. 2021 May;31(3):436–41.

[22] Tang, Y., Rajendran, P., Veeraraghavan, V.P., Hussain, S., Balakrishna. J.P., Chinnathambi, A., et al. 2020, Osteogenic differentiation and mineralization potential of zinc oxide nanoparticles from Scutellaria baicalensis on human osteoblast-like MG-63 cells, Materials Science and Engineering: C, 119, 111656. 

[23] Yin Z, Yang Y, Guo T, Veeraraghavan VP, Wang X. Potential chemotherapeutic effect of betalain against human non-small cell lung cancer through PI3K/Akt/mTOR signaling pathway. Environ Toxicol. 2021 Jun;36(6):1011–20.

[24] Veeraraghavan, V. P., Periadurai, N. D., Karunakaran, T., Hussain, S., Surapaneni, K. M., Jiao, X., 2021, Green synthesis of silver nanoparticles from aqueous extract of Scutellaria barbata and coating on the cotton fabric for antimicrobial applications and wound healing activity in fibroblast cells (L929), Saudi Journal of Biological Sciences, 28(7), 3633–3640.

[25] Mickymaray, S., Alfaiz, F. A., Paramasivam, A., Veeraraghavan, V. P., Periadurai, N. D., Surapaneni, K. M., Niu, G., 2021, Rhaponticin suppresses osteosarcoma through the inhibition of PI3K-Akt-mTOR pathway. Saudi Journal of Biological Sciences, 28(7), 3641–3649.

[26] Teja, K.V., Ramesh, S., 2020, Is a filled lateral canal – A sign of superiority? Journal of Dental Sciences, 15, 562–3.

[27] Kadanakuppe, S., Hiremath, S., 2016, Social and Behavioural Factors Associated with Dental Caries Experience among Adolescent School Children in Bengaluru City, India, British Journal of Medicine and Medical Research. 14, 2016. p. 1–10. 

[28] 28. Garibyan, L., Avashia, N., 2013, Polymerase chain reaction. The Journal of Investigative Dermatology, 133(3), 1–4.

[29] 29. Samadikuchaksaraei, A., 2016, Polymerase Chain Reaction for Biomedical Applications. BoD – Books on Demand, 184.

[30] 30. Li, J. B., Wang, C. Y., Chen, J. W., Feng, Z. Q., Ma, H. T., 2004, Expression of liver insulin-like growth factor 1 gene and its serum level in patients with diabetes. World Journal of Gastroenterology, 10(2), 255–259.

[31] 31. Schofield, P.N., 1992, The Insulin-like Growth Factors: Structure and Biological Functions. Oxford University Press, USA; 284.

[32] 32. Bonavida B, Granger G. Tumor Necrosis Factor: Structure, Mechanism of Action, Role in Disease and Therapy. S Karger Ag; 1990. 252 p.

[33] Jagadheeswari, R., Vishnu Priya, V., Gayathri, R., 2020, Awareness of Vitamin-C Rich Foods Among South Indian Population: A Survey, Journal of Research in Medical and Dental Science, 8(7), 330-338.

[34] Ojastha, B.L., Selvaraj, J., Kavitha, S., Veeraraghavan Vishnu Priya., Gayathri R., 2023, Effect of Argyreia Nervosa on The Expression of Growth Factor Signaling In The Skeletal Muscle Of Streptozotocin-Induced Experimental Diabetic Rats. Journal of Namibian Studies: History Politics Culture, 33, 5942-5950.

[35] Selvi, V.T., Devi, R.G., Jothipriya, A. (2020). Prevalence of dental anxiety among the OP patients in Saveetha Dental College. Drug Invention Today, 14(1).

[36] Vishaka, S., Sridevi, G., Selvaraj, J., 2022, An in vitro analysis on the antioxidant and anti-diabetic properties of Kaempferia galanga rhizome using different solvent systems. Journal of Advanced Pharmaceutical Technology & Research, 13(2), S505–9.

[37] Ealla KKR, Veeraraghavan VP, Ravula NR, Durga CS, Ramani P, Sahu V, Poola PK, Patil S, Panta P (2022) Silk Hydrogel for Tissue Engineering: A Review. J Contemp Dent Pract 23:467–477

[38] Mithil Vora., Vishnu Priya, V., Selvaraj,J., Gayathri, R., Kavitha, S., 2021, Effect of Lupeol on proinflammatory Markers in Adipose Tissue of High-Fat Diet and Sucrose Induced Type-2 Diabetic Rats. Journal of Research in Medical and Dental Science, 9(10),116-121.

[39] Sadasivam, P., Ganapathy, D.M., Sasanka, L.K.,2023, Assessment of Depressive Behaviour among the Undergraduate Dental students-A Survey. Turkish Journal of Physiotherapy and Rehabilitation, 32, 2.

[40] Yasothkumar, D., Jayaraman, S., Ramalingam, K., Ramani, P., 2023. In vitro Anti-Inflammatory and Antioxidant Activity of Seed Ethanolic Extract of Pongamia pinnata. Biomedical and Pharmacology Journal, 16(4). 

[41] Ganesan A, Muthukrishnan A, Veeraraghavan V (2021) Effectiveness of Salivary Glucose in Diagnosing Gestational Diabetes Mellitus. Contemp Clin Dent 12:294–300

[42] Karthik EVG, Priya V (2021) Gayathri. R, Dhanraj Ganapathy. Health Benefits Of Annona Muricata-A Review. Int J Dentistry Oral Sci 8:2965–2967

[43] Priya DV, (2020) Knowledge and awareness on HIV/AIDS among college students in A university hospital setting. Int J Dent Oral Sci 1182–1186

[44] Prakash S, Balaji JN, Veeraraghavan VP, Mohan SK (2022) Telehealth: Is It a Post-COVID Reality in Early Diagnosis of Oral Cancer? J Contemp Dent Pract 23:1181–1182

[45] Priya VV, Sankaran K (2023) Aryl hydrocarbon receptor (AhR) as a potential therapeutic target in oral diseases. World J Dent 14:1–2