Elevated Serum Apelin, Insulin, and IL-17 Levels in Middle-Aged Patients with Type 2 Diabetes Mellitus: Associations with Hepatic Enzyme Alterations
Keywords:
Type 2 diabetes, Apelin, Insulin, IL-17, Hepatic enzymes
Abstract
The "current study investigated changes in serum levels of apelin, insulin, and the pro-inflammatory cytokine interleukin 17 (IL-17) in patients with type 2 diabetes mellitus (type 2 DM). Additionally, as biomarkers for hepatic disorders, serum levels of the liver enzymes ALP, AST, and ALT were assessed in type 2 DM patients aged 40-60 years, with an equal distribution of men and women. Comparative analysis revealed a significant increase (p<0.05) in serum levels of apelin and insulin, with similar trends observed across both genders. Notably, IL-17 levels were also significantly elevated (p<0.05) in the type 2 DM group compared to control subjects. Furthermore, serum levels of ALP, AST, and ALT were significantly higher (p<0.05) in type 2 DM patients than in the control group. These findings, consistent with prior research, indicate that type 2 DM is associated with elevated apelin and IL-17 levels, contributing to significant insulin resistance through complex signaling pathways. Consequently, patients, irrespective of gender but likely influenced by their age (40-60 years), exhibit higher serum insulin levels compared to healthy" controls.
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References
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25. Winn-Deen E S, David H, Sigler G, and Chavez R. Clin Chem.1988;34:2005.
26. German Society for Clinical Chemistry: Recommendations of the Enzyme Commision. Z. Klin. Chem. Klin. Biochem. 1972;10 : 281.
27. Cavallo, M. G., Sentinelli, F., Barchetta, I., Costantino, C., Incani, M., Perra, L. et al. Altered glucose homeostasis is associated with increased serum apelin levels in type 2 diabetes mellitus. PloS one,2012. 7(12), e51236.
28. Soriguer, F., Garrido-Sanchez, L., Garcia-Serrano, S., Garcia-Almeida, J. M., Garcia-Arnes, J., Tinahones, F. J. et al. Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus. Obes. Surg.2009, 19(11), 1574-1580.
29. Krysiak, R., Gdula-Dymek, A., Bachowski, R. and Okopień, B. Pleiotropic effects of atorvastatin and fenofibrate in metabolic syndrome and different types of prediabetes. Diabetes Care,2010. 33: 2266-2270.
30. Heinonen, M. V., Laaksonen, D. E., Karhu, T., Karhunen, L., Laitinen, T., Kainulainen, S. et al. Effect of diet-induced weight loss on plasma apelin and cytokine levels in individuals with the metabolic syndrome. Nutr. Metab. Cardiovasc. Dis.2009, 19(9), 626-633.
31. Nishida, M. and Hamaoka, K. The Apelin–APJ system: Its role in renal physiology and potential therapeutic applications for renal disease. OA Nephrology,2013. 1(1), 7.
32. Freedman, D. S., Dietz, W. H., Srinivasan, S. R., & Berenson, G. S. (1999). The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics, 103(6), 1175-1182.
33. Hamidi, A., Fakhrzadeh, H., Moayyeri, A., Heshmat, R., Ebrahimpour, P., & Larjani, B. (2006). Metabolic syndrome and leptin concentrations in obese children. The Indian Journal of Pediatrics, 73, 593-596.
34. Marwaha, A. K., Leung, N. J., McMurchy, A. N., & Levings, M. K. (2012). TH17 cells in autoimmunity and immunodeficiency: protective or pathogenic?. Frontiers in immunology, 3, 129.
35. Ohshima, K., Mogi, M., Jing, F., Iwanami, J., Tsukuda, K., Min, L. J., ... & Horiuchi, M. (2012). Roles of interleukin 17 in angiotensin ii type 1 receptor–mediated insulin resistance. Hypertension, 59(2), 493499.
36. De Morales, J. M. G. R., Puig, L., Daudén, E., Cañete, J. D., Pablos, J. L., Martín, A. O., ... & González-Gay, M. Á. (2020). Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies. Autoimmunity reviews, 19(1), 102429.
37. Shu, L., Zien, K., Gutjahr, G., Oberholzer, J., Pattou, F., KerrConte, J., & Maedler, K. (2012). TCF7L2 promotes beta cell regeneration in human and mouse pancreas. Diabetologia, 55, 3296-3307.
38. Qiu, A. W., Cao, X., Zhang, W. W., & Liu, Q. H. (2021). IL-17A is involved in diabetic inflammatory pathogenesis by its receptor IL-17RA. Experimental Biology and Medicine, 246(1), 57-65.
39. Al-Salhi, Farah Ghali. Yassin, Israa Ismail. Naji, Nizar Ahmed. Measuring the activity of the alkaline phosphatase enzyme from diabetes testers and partially purifying its analogues. Karbala Journal of Pharmaceutical Sciences 2011.
40. Abdilkarim Yehia J. AL-Sammraie , Al-Mustansiriyah ., Evaluation of Vitamin D Status in Patients with Type 1 Diabetes Mellitus . Journal of Science ,Vol. 26, No 1, 2015
41. Bolkent, S. ; Özlem Saçan2, Ayşe Karatuğ1, Refiye Yanardağ. The Effects of Vitamin B6 on the Liver of Diabetic Rats: A Morphological and Biochemical Study. IUFS Journal of Biology. IUFS. J .Biol. 2008;67(1): 17.
42. Angulo , P and Lindor, K.D. Kuadrennial Review Non-alcoholic fatty liver disease. Journal of Gastroenterology and Hepatology. 2007 21 (1).
43. Farswan, M.; Papiya Mitra Mazumder, V.; Percha. Protective effect of Cassia glauca Linn. on the serum glucose and hepatic enzymes level instreptozotocin induced NIDDM in rats. Indian J. Pharmacol. 2009; 1(41): 19-22.
44. Moller, D. New drug targets for type 2 diabetes and the metabolic syndrome: A review. Nature. 414, 2001; 821-7.
45. Eteng, M. U.; Bassey, B. J.; Atangwho, I. J.; Egbung, G. E.; et al . Biochemical indices of Macrovascular complication in diabetic rat model: compared effects of Vernoia amygdalina, Catharantus roseus and chlorpro pamide", Asia. J. Biochem. 2008; 3: 228- 234.
2. M. A. El-Missiry, M. A. Amer,, F. A. Hemieda, A. I. Othman, D. A. Sakr and H. L. Abdulhad. Cardio ameliorative effect of punicalagin against streptozotocin-induced apoptosis, redox imbalance, metabolic changes and inflammation. Egyptian Journal of Basic and Applied Sciences. 2, 247-260 (2015).
3. S. M. Genuth, J. P. Palmer, and D. M. Nathan. Classification and diagnosis of diabetes.2021.
4. R Cheng, N Taleb, M Stainforth-Dubois, & R Rabasa-Lhoret. The promising future of insulin therapy in diabetes mellitus. American Journal of Physiology-Endocrinology and Metabolism. 320(5), E886-E890 (2021).
5. P Rorsman, F. M. Ashcroft. Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men. Physiol Rev. Jan 1;98(1):117-214.(2018).
6. R Goyal, M Singhal, I Jialal. Type 2 Diabetes. 2023 Jun 23. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 30020625.
7. V Kumar, N Fausto,A. K. Abbas, S Cotran, Ramzi, Robbins , Stanley LRobbins and cotranpathologic Basis of Disease ; 7thEd Philadelphia , Pa:Saunders, Pp.1194-1195 (2005).
8. S Pannain and C Touma. Does lack of sleep cause diabetes .Cleveland Cli. J. med. 2011; 78 (8): 549-58 .
9. C Li, H Cheng, BK Adhikari, S Wang, N Yang, W Liu, J Sun, Y Wang. The Role of Apelin-APJ System in Diabetes and Obesity. Front Endocrinol (Lausanne). Mar 9;13:820002 (2022).
10. Vargas E, Podder V, Carrillo Sepulveda MA. Physiology, Glucose Transporter Type 4. 2023 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 30726007.
11. Dray C, Knauf C, Daviaud D, Waget A, Boucher J, Buléon M, Cani PD, Attané C, Guigné C, Carpéné C, Burcelin R, Castan-Laurell I, Valet P. Apelin stimulates glucose utilization in normal and obese insulin-resistant mice. Cell Metab. 2008 Nov;8(5):437-45. doi: 10.1016/j.cmet.2008.10.003. PMID: 19046574.
12. Kai Chen, Xin-Lan Zhao, Lang-Bo Li, Ling-Yun Huang, Zhuo Tang, Juan Luo, Li Yang, Ai-Ping Qin, Fang Hu,miR-503/Apelin-12 mediates high glucose-induced microvascular endothelial cells injury via JNK and p38MAPK signaling pathway,Regenerative Therapy, Volume 14, 2020, Pages 111-118, ISSN 2352-3204,
13. Sharma B, John S. Nonalcoholic Steatohepatitis (NASH). 2023 Apr 7. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 29262166.
14. Leow WQ, Chan AW, Mendoza PGL, Lo R, Yap K, Kim H. Non-alcoholic fatty liver disease: the pathologist's perspective. Clin Mol Hepatol. 2023 Feb;29(Suppl):S302-S318. doi: 10.3350/cmh.2022.0329. Epub 2022 Nov 15. PMID: 36384146; PMCID: PMC10029955.
15. Moriles KE, Zubair M, Azer SA. Alanine Aminotransferase (ALT) Test. 2024 Feb 27. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 32644704.
16. M. Sue Kirkman, Vanessa Jones Briscoe, Nathaniel Clark, Hermes Florez, Linda B. Haas, Jeffrey B. Halter, Elbert S. Huang, Mary T. Korytkowski, Medha N. Munshi, Peggy Soule Odegard, Richard E. Pratley, Carrie S. Swift; Diabetes in Older Adults. Diabetes Care 1 December 2012; 35 (12): 2650–2664.
17. Assar ME, Angulo J, Rodríguez-Mañas L. Diabetes and ageing-induced vascular inflammation. J Physiol. 2016 Apr 15;594(8):2125-46. doi: 10.1113/JP270841. Epub 2015 Nov 2. PMID: 26435167; PMCID: PMC4933100.
18. Aderinto N, Olatunji G, Abdulbasit M, Ashinze P, Faturoti O, Ajagbe A, Ukoaka B, Aboderin G. The impact of diabetes in cognitive impairment: A review of current evidence and prospects for future investigations. Medicine (Baltimore). 2023 Oct 27;102(43):e35557. doi: 10.1097/MD.0000000000035557. PMID: 37904406; PMCID: PMC10615478.
19. Garber D, Zhu S. Implications of Caspase 1/ Interleukin-1 Beta (IL-1β) Signaling and Hypoxia-Inducible Factor 1-Alpha (HIF-1α) on Diabetic Retinopathy Pathology. Cureus. 2023 Jul 26;15(7):e42479. doi: 10.7759/cureus.42479. PMID: 37637673; PMCID: PMC10451098.
20. Velikova TV, Kabakchieva PP, Assyov YS, Georgiev TА. Targeting Inflammatory Cytokines to Improve Type 2 Diabetes Control. Biomed Res Int. 2021 Sep 13;2021:7297419. doi: 10.1155/2021/7297419. PMID: 34557550; PMCID: PMC8455209.
21. Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther. 2022 Jul 6;7(1):216. doi: 10.1038/s41392-022-01073-0. PMID: 35794109; PMCID: PMC9259665.
22. Yuen DY, Dwyer RM, Matthews VB, Zhang L, Drew BG, Neill B, Kingwell BA, Clark MG, Rattigan S, Febbraio MA. Interleukin-6 attenuates insulin-mediated increases in endothelial cell signaling but augments skeletal muscle insulin action via differential effects on tumor necrosis factor-alpha expression. Diabetes. 2009 May;58(5):1086-95. doi: 10.2337/db08-0775. Epub 2009 Feb 2. PMID: 19188427; PMCID: PMC2671037.
23. Zakir M, Ahuja N, Surksha MA, Sachdev R, Kalariya Y, Nasir M, Kashif M, Shahzeen F, Tayyab A, Khan MSM, Junejo M, Manoj Kumar F, Varrassi G, Kumar S, Khatri M, Mohamad T. Cardiovascular Complications of Diabetes: From Microvascular to Macrovascular Pathways. Cureus. 2023 Sep 24;15(9):e45835. doi: 10.7759/cureus.45835. PMID: 37881393; PMCID: PMC10594042.
24. Garber D, Zhu S. Implications of Caspase 1/ Interleukin-1 Beta (IL-1β) Signaling and Hypoxia-Inducible Factor 1-Alpha (HIF-1α) on Diabetic Retinopathy Pathology. Cureus. 2023 Jul 26;15(7):e42479. doi: 10.7759/cureus.42479. PMID: 37637673; PMCID: PMC10451098.
25. Winn-Deen E S, David H, Sigler G, and Chavez R. Clin Chem.1988;34:2005.
26. German Society for Clinical Chemistry: Recommendations of the Enzyme Commision. Z. Klin. Chem. Klin. Biochem. 1972;10 : 281.
27. Cavallo, M. G., Sentinelli, F., Barchetta, I., Costantino, C., Incani, M., Perra, L. et al. Altered glucose homeostasis is associated with increased serum apelin levels in type 2 diabetes mellitus. PloS one,2012. 7(12), e51236.
28. Soriguer, F., Garrido-Sanchez, L., Garcia-Serrano, S., Garcia-Almeida, J. M., Garcia-Arnes, J., Tinahones, F. J. et al. Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus. Obes. Surg.2009, 19(11), 1574-1580.
29. Krysiak, R., Gdula-Dymek, A., Bachowski, R. and Okopień, B. Pleiotropic effects of atorvastatin and fenofibrate in metabolic syndrome and different types of prediabetes. Diabetes Care,2010. 33: 2266-2270.
30. Heinonen, M. V., Laaksonen, D. E., Karhu, T., Karhunen, L., Laitinen, T., Kainulainen, S. et al. Effect of diet-induced weight loss on plasma apelin and cytokine levels in individuals with the metabolic syndrome. Nutr. Metab. Cardiovasc. Dis.2009, 19(9), 626-633.
31. Nishida, M. and Hamaoka, K. The Apelin–APJ system: Its role in renal physiology and potential therapeutic applications for renal disease. OA Nephrology,2013. 1(1), 7.
32. Freedman, D. S., Dietz, W. H., Srinivasan, S. R., & Berenson, G. S. (1999). The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics, 103(6), 1175-1182.
33. Hamidi, A., Fakhrzadeh, H., Moayyeri, A., Heshmat, R., Ebrahimpour, P., & Larjani, B. (2006). Metabolic syndrome and leptin concentrations in obese children. The Indian Journal of Pediatrics, 73, 593-596.
34. Marwaha, A. K., Leung, N. J., McMurchy, A. N., & Levings, M. K. (2012). TH17 cells in autoimmunity and immunodeficiency: protective or pathogenic?. Frontiers in immunology, 3, 129.
35. Ohshima, K., Mogi, M., Jing, F., Iwanami, J., Tsukuda, K., Min, L. J., ... & Horiuchi, M. (2012). Roles of interleukin 17 in angiotensin ii type 1 receptor–mediated insulin resistance. Hypertension, 59(2), 493499.
36. De Morales, J. M. G. R., Puig, L., Daudén, E., Cañete, J. D., Pablos, J. L., Martín, A. O., ... & González-Gay, M. Á. (2020). Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies. Autoimmunity reviews, 19(1), 102429.
37. Shu, L., Zien, K., Gutjahr, G., Oberholzer, J., Pattou, F., KerrConte, J., & Maedler, K. (2012). TCF7L2 promotes beta cell regeneration in human and mouse pancreas. Diabetologia, 55, 3296-3307.
38. Qiu, A. W., Cao, X., Zhang, W. W., & Liu, Q. H. (2021). IL-17A is involved in diabetic inflammatory pathogenesis by its receptor IL-17RA. Experimental Biology and Medicine, 246(1), 57-65.
39. Al-Salhi, Farah Ghali. Yassin, Israa Ismail. Naji, Nizar Ahmed. Measuring the activity of the alkaline phosphatase enzyme from diabetes testers and partially purifying its analogues. Karbala Journal of Pharmaceutical Sciences 2011.
40. Abdilkarim Yehia J. AL-Sammraie , Al-Mustansiriyah ., Evaluation of Vitamin D Status in Patients with Type 1 Diabetes Mellitus . Journal of Science ,Vol. 26, No 1, 2015
41. Bolkent, S. ; Özlem Saçan2, Ayşe Karatuğ1, Refiye Yanardağ. The Effects of Vitamin B6 on the Liver of Diabetic Rats: A Morphological and Biochemical Study. IUFS Journal of Biology. IUFS. J .Biol. 2008;67(1): 17.
42. Angulo , P and Lindor, K.D. Kuadrennial Review Non-alcoholic fatty liver disease. Journal of Gastroenterology and Hepatology. 2007 21 (1).
43. Farswan, M.; Papiya Mitra Mazumder, V.; Percha. Protective effect of Cassia glauca Linn. on the serum glucose and hepatic enzymes level instreptozotocin induced NIDDM in rats. Indian J. Pharmacol. 2009; 1(41): 19-22.
44. Moller, D. New drug targets for type 2 diabetes and the metabolic syndrome: A review. Nature. 414, 2001; 821-7.
45. Eteng, M. U.; Bassey, B. J.; Atangwho, I. J.; Egbung, G. E.; et al . Biochemical indices of Macrovascular complication in diabetic rat model: compared effects of Vernoia amygdalina, Catharantus roseus and chlorpro pamide", Asia. J. Biochem. 2008; 3: 228- 234.
Published
2025-01-14
How to Cite
Sami Khlaif Mansoor. (2025). Elevated Serum Apelin, Insulin, and IL-17 Levels in Middle-Aged Patients with Type 2 Diabetes Mellitus: Associations with Hepatic Enzyme Alterations. Central Asian Journal of Theoretical and Applied Science, 6(1), 7-15. Retrieved from https://cajotas.centralasianstudies.org/index.php/CAJOTAS/article/view/1532
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