IMPACT OF INSULIN AND MELATONIN ON HEPATIC ANATOMY, CELLULAR BIOCHEMISTRY, AND RECEPTOR EXPRESSION IN DIABETIC HEPATIC DAMAGE

Main Article Content

Dr Bashir Ahmed Chandio
Dr Syed Faizan Ali Shah
Dr Abdullah Khilji
Dr Khalil Ahmed Sanghro

Keywords

Insulin, melatonin, DM, Hepatic injury

Abstract

Objectives:                                                                                                               


To examine the influence of exogenous melatonin and insulin on the biochemical, serological, histological, and receptor expression patterns within liver tissues following hepatic damage.


Materials and Methods:  This observational study was conducted at Ghulam Muhammad Mahar Medical college Sukkur, Pakistan. We have enrolled 74 patients with DM. The study was conducted from July, 2023 to December, 2023. All patients enrolled underwent liver function test and lipid profile. The patients received a combination therapy involving melatonin and insulin. Blood samples were obtained from each participant and forwarded for laboratory analysis. The treatment's efficacy was documented by observing outcomes across all patients. Data collection utilized a predetermined questionnaire.


Results: The mean age and BMI of the entire group of 74 patients were 49.17±9.42 years and 27.31±4.08 (kg/m²) respectively. Our analysis revealed elevated levels of ALT (765.14±154.8), AST (694.59±158.4), ALP (705.70±149.3), serum cholesterol (179.98±8.27), LDL (96.68±3.8), and VLDL (83.37±7.37), accompanied by a reduction in HDL levels (45.22±3.51). Based on Hepatic Anatomy, cirrhosis was observed in 16(21.6%), and fatty liver was observed in 16(21.6%) patients. Hepatic injury recovery was observed in 69 out of 74 cases (93.2%). Remarkable enhancements were detected in the biochemical profile, cellular structure of liver cells, and the expression pattern of MT1, MT2, and IR receptors, suggesting substantial recovery and restoration.


Conclusion: It was concluded that the combined administration of melatonin and insulin among diabetic patients with hepatic injury yielded notably favorable outcomes in terms of effectiveness and disease recuperation. 

Abstract 111 | pdf Downloads 68

References

1. Blüher M. Obesity: global epidemiology and pathogenesis. Nature Reviews Endocrinology. 2019;15(5):288-98.
2. López-Suárez A. Burden of cancer attributable to obesity, type 2 diabetes and associated risk factors. Metabolism. 2019;92:136-46.
3. Popkin BM, Gordon-Larsen P. The nutrition transition: worldwide obesity dynamics and their determinants. International journal of obesity. 2004;28(3):S2-S9.
4. Nabi M, Muhammad A, Subhan Z, Hassan G, Mohammad NS, Salam A, et al. Insulin and Melatonin Modulates the Histo Architecture, Cellular Biochemistry and Receptor Expression During Injury of Hepatic in Diabetic individuals and its treatment. Pakistan Journal of Medical & Health Sciences. 2022;16(08):417-.
5. Arendt J, Aulinas A. Physiology of the pineal gland and melatonin. Endotext [Internet]. 2022.
6. Nikolaev G, Robeva R, Konakchieva R. Membrane melatonin receptors activated cell signaling in physiology and disease. International journal of molecular sciences. 2021;23(1):471.
7. Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS, Slominski AT. Melatonin membrane receptors in peripheral tissues: distribution and functions. Molecular and cellular endocrinology. 2012;351(2):152-66.
8. Schernthaner GH, Schernthaner G. Insulin resistance and inflammation in the early phase of type 2 diabetes: potential for therapeutic intervention. Scandinavian Journal of Clinical and Laboratory Investigation. 2005;65(sup240):30-40.
9. Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre‐Jimenez M, Qin L. Melatonin as an antioxidant: under promises but over delivers. Journal of pineal research. 2016;61(3):253-78.
10. Das J, Acharyya A, Hasan KN. Melatonin: pleiotropic action for the regulation of fish reproduction in aquaculture. Advances in animal science and zoology. 2022;20:55-115.
11. Fadillioglu E, Kurcer Z, Parlakpinar H, Iraz M, Gursul C. Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus. Archives of pharmacal research. 2008;31:705-12.
12. Kurçer Z, Parlakpinar H, Vardi N, Tasdemir S, Iraz M, Fadillioglu E, et al. Protective effects of chronic melatonin treatment against renal ischemia/reperfusion injury in streptozotocin-induced diabetic rats. Experimental and clinical endocrinology & diabetes. 2007;115(06):365-71.
13. Peschke E, Mühlbauer E. New evidence for a role of melatonin in glucose regulation. Best practice & research Clinical endocrinology & metabolism. 2010;24(5):829-41.
14. Rai S, Hajam YA, Basheer M, Ghosh H. Biochemical and histopathological inflections in hepato-renal tissues of streptozotocin (STZ) induced diabetic male rats: Impact of exogenous melatonin administration. J Clin Res Bioeth. 2016;7(2).
15. Gupta S, Nayak MT, Sunitha J, Dawar G, Sinha N, Rallan NS. Correlation of salivary glucose level with blood glucose level in diabetes mellitus. Journal of oral and maxillofacial pathology: JOMFP. 2017;21(3):334.
16. PJ L, Sanchez N A-S, JM G. Melatonin and glucose metabolism: clinical relevance. Current pharmaceutical design. 2014;20(30):4841-53.
17. Mayo JC, Aguado A, Cernuda-Cernuda R, Álvarez-Artime A, Cepas V, Quirós-González I, et al. Melatonin uptake by cells: an answer to its relationship with glucose? Molecules. 2018;23(8):1999.
18. Qaid MM, Abdelrahman MM. Role of insulin and other related hormones in energy metabolism—A review. Cogent Food & Agriculture. 2016;2(1):1267691.
19. Kanter M, Uysal H, Karaca T, Sagmanligil HO. Depression of glucose levels and partial restoration of pancreatic β-cell damage by melatonin in streptozotocin-induced diabetic rats. Archives of toxicology. 2006;80:362-9.
20. Richardson A, Park WG. Acute pancreatitis and diabetes mellitus: a review. The Korean journal of internal medicine. 2021;36(1):15.
21. Szkudelski T. Streptozotocin–nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Experimental biology and medicine. 2012;237(5):481-90.
22. Kosmachevskaya OV, Novikova NN, Topunov AF. Carbonyl stress in red blood cells and hemoglobin. Antioxidants. 2021;10(2):253.
23. Taskin E, Guven C, Kaya ST, Sahin L, Kocahan S, Degirmencioglu AZ, et al. The role of toll-like receptors in the protective effect of melatonin against doxorubicin-induced pancreatic beta cell toxicity. Life sciences. 2019;233:116704.
24. Ostadmohammadi V, Soleimani A, Bahmani F, Aghadavod E, Ramezani R, Reiter RJ, et al. The effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis patients: a randomized, double-blind, placebo-controlled trial. Journal of renal nutrition. 2020;30(3):242-50.
25. Karamitri A, Renault N, Clement N, Guillaume J-L, Jockers R. Minireview: Toward the establishment of a link between melatonin and glucose homeostasis: association of melatonin MT2 receptor variants with type 2 diabetes. Molecular endocrinology. 2013;27(8):1217-33.
26. Bähr I, Mühlbauer E, Albrecht E, Peschke E. Evidence of the receptor‐mediated influence of melatonin on pancreatic glucagon secretion via the Gαq protein‐coupled and PI3K signaling pathways. Journal of Pineal Research. 2012;53(4):390-8.
27. Batty I, Hickinson D, Downes C. Cross-talk between phospholipase C and phosphoinositide 3-kinase signalling pathways. Biochemical Society Transactions. 1997;25(4):1132-7