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Abstract
Background: Deficiency of vitamin B12 remains a health problem in both developed and developing countries. Many journal studies showed an association between deficiency of vitamin B12 and metabolic disorder, one of which is insulin resistance, one of the most significant metabolic diseases. Resistance to insulin may be assessed by changes in plasma glucose and insulin levels. This study explored a possible relationship between vitamin B12 restriction and glucose metabolism.
Materials and Methods: This study used an experimental method of 18 male Sprague Dawley rats (Rattus norvegicus, 300-400 gram, age 7-8 months), divided into three groups: control (G1), four weeks treatment group (G2 ) and 12-week treatment group (G3). In the control group, regular feed, the standard diet was given, while the treatment group was assigned vitamin B12, AIN-93M deficiency feed according to the treatment age.
Results: Plasma glucose increased in treatment group after 4 weeks (control vs P1= 104.7 ± 5.04 vs 206.8 ± 4.5 p = 0.000) and 12 weeks (control vs P3 = 99.9±6.3 vs 144.7±6.8 p<0.01). Plasma insulin decreased in treatment group after 4 weeks (control vs P1=63.8 ± 1.5 vs 59.9 ± 0.7 p > 0.05) and 12 weeks (control vs P3 = 61.5±0.64 vs 57.4±1 p>0.05).
Conclusion: Increased homocysteine deficiency due to dietary vitamin B12 can cause insulin resistance syndrome. As a result, glucose and plasma insulin levels are disrupted
Keywords: Homocysteine, vitamin B12 Deficiency, Glucose, Insulin, Insulin Resistance
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References
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- Pessin JE, Saltiel AR. Signaling pathways in insulin action : molecular targets of insulin resistance. J Clin Invest. 2000;106(2):165–9.
- Schmitz-peiffer C. Signalling aspects of insulin resistance in skeletal muscle : mechanisms induced by lipid oversupply. 2010;12(2000):583–94.
- Golbahar J, Aminzadeh MA, Kassab SE, Omrani GR. Hyperhomocysteinemia induces insulin resistance in male Sprague-Dawley rats. Diabetes Res Clin Pract. 2007;76(1):1–5.
- Najib S, Sánchez-Margalet V. Homocysteine thiolactone inhibits insulin-stimulated DNA and protein synthesis: Possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation. J Mol Endocrinol. 2005;34(1):119–26.
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- Jakubowski H. Molecular basis of homocysteine toxicity in humans. Cell Mol Life Sci. 2004;61(4):470–87.
- Undas A, PerÅ‚a J, Åacinski M, Trzeciak W, Kaźmierski R, Jakubowski H. Autoantibodies against N-homocysteinylated proteins in humans: Implications for atherosclerosis. Stroke. 2004;35(6):1299–304.
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- Ai Y, Sun Z, Peng C, Liu L, Xiao X, Li J. Homocysteine induces hepatic steatosis involving ER stress response in high methionine diet-fedmice. Nutrients. 2017;9(4):1–10.
- Oh RC, Hustead TR, Ali SM, Pantsari MW. Mildly Elevated Liver Transaminase Levels: Causes and Evaluation. Am Fam Physician. 2017;96(11):709–15.
- Lebeaupin C, Vallée D, Hazari Y, Hetz C, Chevet E, Bailly-Maitre B. Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. J Hepatol [Internet]. 2018;69(4):927–47. Available from: https://doi.org/10.1016/j.jhep.2018.06.008
- Rencurel F, Waeber G, Antoine B, Rocchiccioli F, Maulard P, Girard J, et al. Requirement of glucose metabolism for regulation of glucose transporter type 2 (GLUT2) gene expression in liver. Biochem J [Internet]. 1996;314 ( Pt 3:903–9. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1217142&tool=pmcentrez&rendertype=abstract
- Lee J, Kang HS, Park HY, Moon Y, Kang YN, Oh B, et al. OPEN PPAR α -dependent Insig2a overexpression inhibits SREBP-1c processing during fasting. Sci Rep [Internet]. 2017;(May):1–12. Available from: http://dx.doi.org/10.1038/s41598-017-10523-7
- Purwanto B, Sudiana IK, Herawati L, Aksono B. Muscle Glucose Transporter 1 ( Glut-1 ) Expression in Diabetic Rat Models. FOlia Medica Indones. 2013;49:21–5.
- Sharma RS, Harrison DJ, Kisielewski D, Cassidy DM, McNeilly AD, Gallagher JR, et al. Experimental Nonalcoholic Steatohepatitis and Liver Fibrosis Are Ameliorated by Pharmacologic Activation of Nrf2 (NF-E2 p45-Related Factor 2). Cmgh [Internet]. 2018;5(3):367–98. Available from: https://doi.org/10.1016/j.jcmgh.2017.11.016
References
Yu X, Huang Y, Hu Q, Ma L. Hyperhomocysteinemia stimulates hepatic glucose output and PEPCK expression. Acta Biochim Biophys Sin (Shanghai). 2009;41(12):1027–32.
Pessin JE, Saltiel AR. Signaling pathways in insulin action : molecular targets of insulin resistance. J Clin Invest. 2000;106(2):165–9.
Schmitz-peiffer C. Signalling aspects of insulin resistance in skeletal muscle : mechanisms induced by lipid oversupply. 2010;12(2000):583–94.
Golbahar J, Aminzadeh MA, Kassab SE, Omrani GR. Hyperhomocysteinemia induces insulin resistance in male Sprague-Dawley rats. Diabetes Res Clin Pract. 2007;76(1):1–5.
Najib S, Sánchez-Margalet V. Homocysteine thiolactone inhibits insulin-stimulated DNA and protein synthesis: Possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation. J Mol Endocrinol. 2005;34(1):119–26.
Gammon CS, von Hurst PR, Coad J, Kruger R, Stonehouse W. Vegetarianism, vitamin B12 status, and insulin resistance in a group of predominantly overweight/obese South Asian women. Nutrition [Internet]. 2012;28(1):20–4. Available from: http://dx.doi.org/10.1016/j.nut.2011.05.006
Santoso DIS, Murthi AK, Yolanda S, Amani P, Ujianti I, Sianipar IR. The impact of cobalamin deficiency on heart function: A study on abnormalities in electrocardiography patterns. Int J Appl Pharm. 2019;11(Special Issue 6).
Amani P, Prijanti AR, Jusuf AA, Kartinah NT, Ujianti I, Murthi AK, et al. Cobalamin restriction with AIN-93M chow modification: Hematology and cardiovascular parameter assessment. In: AIP Conference Proceedings. 2019.
Kumari C, Kapoor S, Varughese B, Pollipali SK, Ramji S. Mutation Analyses in Selected Exons of the MUT Gene in Indian Patients with Methylmalonic Acidemia. Indian J Clin Biochem. 2017;32(3):266–74.
Jakubowski H. Molecular basis of homocysteine toxicity in humans. Cell Mol Life Sci. 2004;61(4):470–87.
Undas A, PerÅ‚a J, Åacinski M, Trzeciak W, Kaźmierski R, Jakubowski H. Autoantibodies against N-homocysteinylated proteins in humans: Implications for atherosclerosis. Stroke. 2004;35(6):1299–304.
Najib S, Sánchez-Margalet V. Homocysteine thiolactone inhibits insulin signaling, and glutathione has a protective effect. J Mol Endocrinol. 2001;27(1):85–91.
Li Z, Gueant-Rodriguez RM, Quilliot D, Sirveaux MA, Meyre D, Gueant JL, et al. Folate and vitamin B12 status is associated with insulin resistance and metabolic syndrome in morbid obesity. Clin Nutr [Internet]. 2017;(July):1–7. Available from: http://dx.doi.org/10.1016/j.clnu.2017.07.008
Ai Y, Sun Z, Peng C, Liu L, Xiao X, Li J. Homocysteine induces hepatic steatosis involving ER stress response in high methionine diet-fedmice. Nutrients. 2017;9(4):1–10.
Oh RC, Hustead TR, Ali SM, Pantsari MW. Mildly Elevated Liver Transaminase Levels: Causes and Evaluation. Am Fam Physician. 2017;96(11):709–15.
Lebeaupin C, Vallée D, Hazari Y, Hetz C, Chevet E, Bailly-Maitre B. Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. J Hepatol [Internet]. 2018;69(4):927–47. Available from: https://doi.org/10.1016/j.jhep.2018.06.008
Rencurel F, Waeber G, Antoine B, Rocchiccioli F, Maulard P, Girard J, et al. Requirement of glucose metabolism for regulation of glucose transporter type 2 (GLUT2) gene expression in liver. Biochem J [Internet]. 1996;314 ( Pt 3:903–9. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1217142&tool=pmcentrez&rendertype=abstract
Lee J, Kang HS, Park HY, Moon Y, Kang YN, Oh B, et al. OPEN PPAR α -dependent Insig2a overexpression inhibits SREBP-1c processing during fasting. Sci Rep [Internet]. 2017;(May):1–12. Available from: http://dx.doi.org/10.1038/s41598-017-10523-7
Purwanto B, Sudiana IK, Herawati L, Aksono B. Muscle Glucose Transporter 1 ( Glut-1 ) Expression in Diabetic Rat Models. FOlia Medica Indones. 2013;49:21–5.
Sharma RS, Harrison DJ, Kisielewski D, Cassidy DM, McNeilly AD, Gallagher JR, et al. Experimental Nonalcoholic Steatohepatitis and Liver Fibrosis Are Ameliorated by Pharmacologic Activation of Nrf2 (NF-E2 p45-Related Factor 2). Cmgh [Internet]. 2018;5(3):367–98. Available from: https://doi.org/10.1016/j.jcmgh.2017.11.016