Expanding arsenal against diabetic neuropathy through betaine: Success so far and bottlenecks
Vol 8, Issue 2, 2024
VIEWS - 120 (Abstract) 53 (PDF)
Abstract
Diabetes mellitus is one of the main chronic metabolic syndromes that contains a number of repercussions and risk factors because hyperglycemia leads other organs to malfunction. Despite the existence of cutting-edge methods for the treatment of diabetes, the proper therapeutic medication distribution remains a serious worry in the current situation. Betaine, also known as N,N-trimethyl glycine, is an amino acid derivative with a number of advantageous health effects. This chemical is available to both humans and other animals because it is consumed and created endogenously. Additionally, some pathological conditions, such as type 2 diabetes, result in a decrease in the amount of betaine in the tissues. Betaine has been found in rodent studies to considerably lessen a number of abnormalities associated with diabetes. changes in the liver and other insulin-sensitive organs. Researchers believe that AMP-activated protein kinase is crucial to the mechanism through which betaine exerts its anti-diabetic effects. Also, betaine has been demonstrated to reduce endoplasmic reticulum stress and inflammation in rodent models of diabetes. Since betaine has shown promising therapeutic benefits in animal trials, its potential use in treating diabetes has been raised.
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1. Mire-Sluis A, Das AR. Lernmark, American diabetes association. Diabetes/metabolism research and reviews. 1999; 15(1): 78-79.
2. Solis-Herrera C, Triplitt C, Pharm D, et al. Pathogenesis of type 2 diabetes mellitus. Endotext; 2021.
3. Federation I. IDF Diabetes Atlas, tenth. International Diabetes. 2021.
4. Abraham MM, Tyng TS, Rekha K, et al. Comparison of Four Screening Methods for Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus Patients: A Cross Sectional Study. Research Journal of Pharmacy and Technology. 2018; 11(12): 5551. doi: 10.5958/0974-360x.2018.01010.7
5. Awasthi A, Singh SK, Kumar B, et al. Treatment Strategies Against Diabetic Foot Ulcer: Success so Far and the Road Ahead. Current Diabetes Reviews. 2021; 17(4): 421-436. doi: 10.2174/1573399816999201102125537
6. Padhi S, Nayak AK, Behera A. Type II diabetes mellitus: a review on recent drug based therapeutics. Biomedicine & Pharmacotherapy. 2020; 131: 110708. doi: 10.1016/j.biopha.2020.110708
7. Cheng AYY. Oral antihyperglycemic therapy for type 2 diabetes mellitus. Canadian Medical Association Journal. 2005; 172(2): 213-226. doi: 10.1503/cmaj.1031414
8. Arumugam MK, Paal MC, Donohue TM, et al. Beneficial Effects of Betaine: A Comprehensive Review. Biology. 2021; 10(6): 456. doi: 10.3390/biology10060456
9. Truitt C, Hoff WD, Deole R. Health Functionalities of Betaine in Patients with Homocystinuria. Frontiers in Nutrition. 2021; 8. doi: 10.3389/fnut.2021.690359
10. Chen ST, Hsieh CP, Lee MY, et al. Betaine prevents and reverses the behavioral deficits and synaptic dysfunction induced by repeated ketamine exposure in mice. Biomedicine & Pharmacotherapy. 2021; 144: 112369. doi: 10.1016/j.biopha.2021.112369
11. Jadhav G, Deshmukh A, Mundlod K. Effect of Linagliptin and Niclosamide on Streptozotocin Induced Diabetic Neuropathy in Rats. Research J. Pharm. and Tech. 2020; 13(5): 2101-2106. doi: 10.5958/0974-360X.2020.00378.9
12. Katulanda P, Ranasinghe P, Jayawardena R, et al. The prevalence, patterns and predictors of diabetic peripheral neuropathy in a developing country. Diabetology & Metabolic Syndrome. 2012; 4(1). doi: 10.1186/1758-5996-4-21
13. Kaur H, Kaur A, Kumar Prashar P, et al. Clinical Impact of Combination Therapy in Diabetic Neuropathy and Nephropathy. Research Journal of Pharmacy and Technology. 2021: 3471-3480. doi: 10.52711/0974-360x.2021.00603
14. Oyenihi AB, Ayeleso AO, Mukwevho E, et al. Antioxidant Strategies in the Management of Diabetic Neuropathy. BioMed Research International. 2015; 2015: 1-15. doi: 10.1155/2015/515042
15. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2016; 40(1): 136-154. doi: 10.2337/dc16-2042
16. Ahmad SI. Diabetes. Springer New York; 2012. doi: 10.1007/978-1-4614-5441-0
17. Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: An overview. Avicenna journal of medicine. 2020; 10(04): 174-188. doi: 10.4103/ajm.ajm_53_20
18. Boulton AJM, Vinik AI, Arezzo JC, et al. Diabetic Neuropathies. Diabetes Care. 2005; 28(4): 956-962. doi: 10.2337/diacare.28.4.956
19. Feldman E. The Diabetes Mellitus Manual. McGraw-Hill New York; 2005.
20. Feldman E, Sullivan K, Lentz S, et al. J. Criteria for Creating and Assessing Mouse Models of Diabetic Neuropathy. Current Drug Targets. 2008; 9(1): 3-13. doi: 10.2174/138945008783431763
21. Ghezzi P, Cerami A. Tissue-Protective Cytokines. Humana Press; 2013. doi: 10.1007/978-1-62703-308-4
22. Polydefkis M, Hauer P, Sheth S, et al. The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain. 2004; 127(7): 1606-1615. doi: 10.1093/brain/awh175
23. Hsu WC, Chiu YH, Chen WH, et al. Simplified Electrodiagnostic Criteria of Diabetic Polyneuropathy in Field Study (KCIS No. 14). Neuroepidemiology. 2007; 28(1): 50-55. doi: 10.1159/000098517
24. Hébert HL, Veluchamy A, Torrance N, et al. Risk factors for neuropathic pain in diabetes mellitus. Pain. 2016; 158(4): 560-568. doi: 10.1097/j.pain.0000000000000785
25. Raputova J, Srotova I, Vlckova E, et al. Sensory phenotype and risk factors for painful diabetic neuropathy: a cross-sectional observational study. Pain. 2017; 158(12): 2340-2353. doi: 10.1097/j.pain.0000000000001034
26. Themistocleous AC, Ramirez JD, Shillo PR, et al. The Pain in Neuropathy Study (PiNS). Pain. 2016; 157(5): 1132-1145. doi: 10.1097/j.pain.0000000000000491
27. Keller JN, Hanni KB, Markesbery WR. Oxidized Low‐Density Lipoprotein Induces Neuronal Death. Journal of Neurochemistry. 1999; 72(6): 2601-2609. doi: 10.1046/j.1471-4159.1999.0722601.x
28. Cerf ME. Beta Cell Dysfunction and Insulin Resistance. Frontiers in Endocrinology. 2013; 4. doi: 10.3389/fendo.2013.00037
29. Bunney PE, Zink AN, Holm AA, et al. Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet. Physiology & Behavior. 2017; 176: 139-148. doi: 10.1016/j.physbeh.2017.03.040
30. Fu Z R, Gilbert E, Liu D. Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes. Current Diabetes Reviews. 2013; 9(1): 25-53. doi: 10.2174/157339913804143225
31. Halban PA. Proinsulin processing in the regulated and the constitutive secretory pathway. Diabetologia. 1994; 37(S2): S65-S72. doi: 10.1007/bf00400828
32. Boland BB, Rhodes CJ, Grimsby JS. The dynamic plasticity of insulin production in β-cells. Molecular Metabolism. 2017; 6(9): 958-973. doi: 10.1016/j.molmet.2017.04.010
33. Rorsman P, Ashcroft FM. Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men. Physiological Reviews. 2018; 98(1): 117-214. doi: 10.1152/physrev.00008.2017
34. Seino S, Shibasaki T, Minami K. Dynamics of insulin secretion and the clinical implications for obesity and diabetes. Journal of Clinical Investigation. 2011; 121(6): 2118-2125. doi: 10.1172/jci45680
35. Islam MdS. The Ryanodine Receptor Calcium Channel of β-Cells. Diabetes. 2002; 51(5): 1299-1309. doi: 10.2337/diabetes.51.5.1299
36. Cuíñas A, García-Morales V, Viña D, et al. Activation of PKA and Epac proteins by cyclic AMP depletes intracellular calcium stores and reduces calcium availability for vasoconstriction. Life Sciences. 2016; 155: 102-109. doi: 10.1016/j.lfs.2016.03.059
37. Lustig KD, Shiau AK, Brake AJ, et al. Expression cloning of an ATP receptor from mouse neuroblastoma cells. Proceedings of the National Academy of Sciences. 1993; 90(11): 5113-5117. doi: 10.1073/pnas.90.11.5113
38. Simon J, Webb TE, King BF, et al., Characterisation of a recombinant P2Y purinoceptor. European Journal of Pharmacology: Molecular Pharmacology. 1995; 291(3): 281-289. doi: 10.1016/0922-4106(95)90068-3
39. Valera S, Hussy N, Evans RJ, et al. A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP. Nature. 1994; 371(6497): 516-519. doi: 10.1038/371516a0
40. Blachier F, Malaisse W. Effect of exogenous ATP upon inositol phosphate production, cationic fluxes and insulin release in pancreatic islet cells. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 1988; 970(2): 222-229. doi. 10.1016/0167-4889(88)90182-6
41. Li G, Milani D, Dunne MJ, et al. Extracellular ATP causes Ca2(+)-dependent and-independent insulin secretion in RINm5F cells. Phospholipase C mediates Ca2+ mobilization but not Ca2+ influx and membrane depolarization. Journal of Biological Chemistry. 1991; 266(6): 3449-3457. doi: 10.1016/S0021-9258(19)67816-6
42. Christensen AA, Gannon M. The Beta Cell in Type 2 Diabetes. Current Diabetes Reports. 2019; 19(9). doi: 10.1007/s11892-019-1196-4
43. Halban PA, Polonsky KS, Bowden DW, et al. β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment. The Journal of Clinical Endocrinology & Metabolism. 2014; 99(6): 1983-1992. doi: 10.1210/jc.2014-1425
44. Yamamoto WR, Bone RN, Sohn P, et al. Endoplasmic reticulum stress alters ryanodine receptor function in the murine pancreatic β cell. Journal of Biological Chemistry. 2019; 294(1): 168-181. doi: 10.1074/jbc.ra118.005683
45. Hoang DO, Thorn P. Insulin secretion from beta cells within intact islets: Location matters. Clinical and Experimental Pharmacology and Physiology. 2015; 42(4): 406-414. doi: 10.1111/1440-1681.12368
46. Liu M, Weiss MA, Arunagiri A, et al. Biosynthesis, structure, and folding of the insulin precursor protein. Diabetes, Obesity and Metabolism. 2018; 20(S2): 28-50. doi: 10.1111/dom.13378
47. Dilger RN, Garrow TA, Baker DH. Betaine Can Partially Spare Choline in Chicks but Only When Added to Diets Containing a Minimal Level of Choline. The Journal of Nutrition. 2007; 137(10): 2224-2228. doi: 10.1093/jn/137.10.2224
48. Ganu RS, Ishida Y, Koutmos M, et al. Evolutionary Analyses and Natural Selection of Betaine-Homocysteine S-Methyltransferase (BHMT) and BHMT2 Genes. PLOS ONE. 2015; 10(7): e0134084. doi: 10.1371/journal.pone.0134084
49. Slow S, Donaggio M, Cressey PJ, et al. The betaine content of New Zealand foods and estimated intake in the New Zealand diet. Journal of Food Composition and Analysis. 2005; 18(6): 473-485. doi: 10.1016/j.jfca.2004.05.004
50. Olthof M, Verhoef P. Effects of Betaine Intake on Plasma Homocysteine Concentrations and Consequences for Health. Current Drug Metabolism. 2005; 6(1): 15-22. doi: 10.2174/1389200052997366
51. Atkinson W, Downer P, Lever M, et al. Effects of orange juice and proline betaine on glycine betaine and homocysteine in healthy male subjects. European Journal of Nutrition. 2007; 46(8): 446-452. doi: 10.1007/s00394-007-0684-5
52. Lever M, Slow S. The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clinical Biochemistry. 2010; 43(9): 732-744. doi: 10.1016/j.clinbiochem.2010.03.009
53. Rosas-Rodríguez JA, Valenzuela-Soto EM. The glycine betaine role in neurodegenerative, cardiovascular, hepatic, and renal diseases: Insights into disease and dysfunction networks. Life Sciences. 2021; 285: 119943. doi: 10.1016/j.lfs.2021.119943
54. Craig SA. Betaine in human nutrition. The American Journal of Clinical Nutrition. 2004; 80(3): 539-549. doi: 10.1093/ajcn/80.3.539
55. Mahmoud AM, Ali MM. Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome. Nutrients. 2019; 11(3): 608. doi: 10.3390/nu11030608
56. Konstantinova SV, Tell GS, Vollset SE, et al. Dietary patterns, food groups, and nutrients as predictors of plasma choline and betaine in middle-aged and elderly men and women. The American Journal of Clinical Nutrition. 2008; 88(6): 1663-1669. doi: 10.3945/ajcn.2008.26531
57. Lever M, George PM, Atkinson W, et al. Plasma Lipids and Betaine Are Related in an Acute Coronary Syndrome Cohort. Tomé D, ed. PLoS ONE. 2011; 6(7): e21666. doi: 10.1371/journal.pone.0021666
58. Slow S, Lever M, Chambers S, et al. Plasma dependent and independent accumulation of betaine in male and female rat tissues. Physiological Research. Published online 2009: 403-410. doi: 10.33549/physiolres.931569
59. Schwab U, Törrönen A, Meririnne E, et al. Orally Administered Betaine Has an Acute and Dose-Dependent Effect on Serum Betaine and Plasma Homocysteine Concentrations in Healthy Humans. The Journal of Nutrition. 2006; 136(1): 34-38. doi: 10.1093/jn/136.1.34
60. Atkinson W, Slow S, Elmslie J, et al. Dietary and supplementary betaine: Effects on betaine and homocysteine concentrations in males. Nutrition, Metabolism and Cardiovascular Diseases. 2009; 19(11): 767-773. doi: 10.1016/j.numecd.2009.01.004
61. Lever M, Sizeland PCM, Frampton CM, et al. Short and long-term variation of plasma glycine betaine concentrations in humans. Clinical Biochemistry. 2004; 37(3): 184-190. doi: 10.1016/j.clinbiochem.2003.11.004
62. Lever M, Atkinson W, Sizeland PCB, et al. Inter- and intra-individual variations in normal urinary glycine betaine excretion. Clinical Biochemistry. 2007; 40(7): 447-453. doi: 10.1016/j.clinbiochem.2006.10.029
63. Lever M, Atkinson W, Slow S, et al. Plasma and urine betaine and dimethylglycine variation in healthy young male subjects. Clinical Biochemistry. 2009; 42(7-8): 706-712. doi: 10.1016/j.clinbiochem.2009.02.001
64. Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011; 472(7341): 57-63. doi: 10.1038/nature09922
65. Holm PI, Bleie Ø, Ueland PM, et al. Betaine as a Determinant of Postmethionine Load Total Plasma Homocysteine Before and After B-Vitamin Supplementation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2004; 24(2): 301-307. doi: 10.1161/01.atv.0000114569.54976.31
66. Ueland PM, Holm PI, Hustad S. Betaine: a key modulator of one-carbon metabolism and homocysteine status. Clinical Chemistry and Laboratory Medicine (CCLM). 2005; 43(10). doi: 10.1515/cclm.2005.187
67. Bønaa KH, Njølstad I, Ueland PM, et al. Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction. New England Journal of Medicine. 2006; 354(15): 1578-1588. doi: 10.1056/nejmoa055227
68. Lonn E. Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. Nat Clin Pract Cardiovasc Med. 2006; 3: 414-415.
69. Albert CM, Cook NR, Gaziano JM, et al. Effect of Folic Acid and B Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease. JAMA. 2008; 299(17): 2027. doi: 10.1001/jama.299.17.2027
70. Kettunen H, Peuranen S, Tiihonen K, et al. Intestinal uptake of betaine in vitro and the distribution of methyl groups from betaine, choline, and methionine in the body of broiler chicks. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology. 2001; 128(2): 269-278. doi: 10.1016/S1095-6433(00)00301-9
71. Kettunen H, Tiihonen K, Peuranen S, et al. Dietary betaine accumulates in the liver and intestinal tissue and stabilizes the intestinal epithelial structure in healthy and coccidia-infected broiler chicks. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology. 2001; 130(4): 759-769. doi: 10.1016/S1095-6433(01)00410-X
72. Craig SS, Craig SA, Ganio MS, et al. The betaine content of sweat from adolescent females. Journal of the International Society of Sports Nutrition. 2010; 7(1). doi: 10.1186/1550-2783-7-3
73. Nijhout HF, Reed MC, Lam SL, et al. In silico experimentation with a model of hepatic mitochondrial folate metabolism. Theoretical Biology and Medical Modelling. 2006; 3(1). doi: 10.1186/1742-4682-3-40
74. Suarez MC, Machado CJV, Lima LMTR, et al. Role of Hydration in the Closed-to-Open Transition Involved in Ca2+ Binding by Troponin C. Biochemistry. 2003; 42(18): 5522-5530. doi: 10.1021/bi027102h
75. Matz RL. (1) The Relationship of Protein Expression and Cell Division, (2) 3D Imaging of Cells Using Digital Holography, and (3) General Chemistry Enrollment at University of Michigan. University of Michigan; 2012.
76. Lang F. Mechanisms and Significance of Cell Volume Regulation. Journal of the American College of Nutrition. 2007; 26(sup5): 613S-623S. doi: 10.1080/07315724.2007.10719667
77. Yamauchi A, Uchida S, Kwon HM, et al. Cloning of a Na(+)- and Cl(-)-dependent betaine transporter that is regulated by hypertonicity. Journal of Biological Chemistry. 1992; 267(1): 649-652. doi: 10.1016/S0021-9258(18)48543-2
78. Kempson SA, Montrose MH. Osmotic regulation of renal betaine transport: transcription and beyond. Pflgers Archiv—European Journal of Physiology. 2004; 449(3): 227-234. doi: 10.1007/s00424-004-1338-6
79. Denkert C, Warskulat U, Hensel F, et al. Osmolyte Strategy in Human Monocytes and Macrophages: Involvement of p38MAPKin Hyperosmotic Induction of Betaine and Myoinositol Transporters. Archives of Biochemistry and Biophysics. 1998; 354(1): 172-180. doi: 10.1006/abbi.1998.0661
80. Olsen M, Sarup A, Larsson OM, et al. Effect of Hyperosmotic Conditions on the Expression of the Betaine-GABA-Transporter (BGT-1) in Cultured Mouse Astrocytes. Neurochemical Research. 2005; 30(6-7): 855-865. doi: 10.1007/s11064-005-6879-3
81. Thwaites DT, Anderson CMH. Deciphering the mechanisms of intestinal imino (and amino) acid transport: The redemption of SLC36A1. Biochimica et Biophysica Acta (BBA)—Biomembranes. 2007; 1768(2): 179-197. doi: 10.1016/j.bbamem.2006.10.001
82. Petronini PG, Alfieri RR, Losio MN, et al. Induction of BGT-1 and amino acid System A transport activities in endothelial cells exposed to hyperosmolarity. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2000; 279(5): R1580-R1589. doi: 10.1152/ajpregu.2000.279.5.r1580
83. Alfieri RR, Cavazzoni A, Petronini PG, et al. Compatible osmolytes modulate the response of porcine endothelial cells to hypertonicity and protect them from apoptosis. The Journal of Physiology. 2002; 540(2): 499-508. doi: 10.1113/jphysiol.2001.013395
84. Häussinger D. The role of cellular hydration in the regulation of cell function. Biochemical Journal. 1996; 313(3): 697-710. doi: 10.1042/bj3130697
85. Yancey PH, Somero GN. Counteraction of urea destabilization of protein structure by methylamine osmoregulatory compounds of elasmobranch fishes. Biochemical Journal. 1979; 183(2): 317-323. doi: 10.1042/bj1830317
86. Delgado-Reyes CV, Garrow TA. High sodium chloride intake decreases betaine-homocysteineS-methyltransferase expression in guinea pig liver and kidney. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2005; 288(1): R182-R187. doi: 10.1152/ajpregu.00406.2004
87. Xu B, Hu Y, Luo YT, et al. Changes in expression of follicular glucose transporters may be involved in ovarian function impairment during diabetic hyperglycemia. Annals of Clinical & Laboratory Science. 2019; 49(6): 785-793.
88. Samie KA, Tabandeh MR, Afrough M. Betaine ameliorates impaired steroidogenesis and apoptosis in mice granulosa cells induced by high glucose concentration. Systems Biology in Reproductive Medicine. 2020; 66(6): 400-409. doi: 10.1080/19396368.2020.1811423
89. Norris OC, Schermerhorn T. The mean cell volume difference (dMCV) reflects serum hypertonicity in diabetic dogs. PLOS ONE. 2019; 14(7): e0219864. doi: 10.1371/journal.pone.0219864
90. Burgos JI, Morell M, Mariángelo JIE, et al. Hyperosmotic stress promotes endoplasmic reticulum stress-dependent apoptosis in adult rat cardiac myocytes. Apoptosis. 2019; 24(9-10): 785-797. doi: 10.1007/s10495-019-01558-4
91. Pihán P, Carreras-Sureda A, Hetz C. BCL-2 family: integrating stress responses at the ER to control cell demise. Cell Death & Differentiation. 2017; 24(9): 1478-1487. doi: 10.1038/cdd.2017.82
92. Zhao G, He F, Wu C, et al. Betaine in Inflammation: Mechanistic Aspects and Applications. Frontiers in Immunology. 2018; 9. doi: 10.3389/fimmu.2018.01070
93. Tripathi M, Zhang CW, Singh BK, et al. Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation. Cell Death & Disease. 2016; 7(12): e2513-e2513. doi: 10.1038/cddis.2016.374
94. Nazari M, Moghimipour E, Tabandeh MR. Betaine Down Regulates Apelin Gene Expression in Cardiac and Adipose Tissues of Insulin Resistant Diabetic Rats Fed by High-Calorie Diet. International Journal of Peptide Research and Therapeutics. 2016; 23(2): 181-190. doi: 10.1007/s10989-016-9551-7
95. Park SW, Jun HOH, Kwon E, et al. Antiangiogenic effect of betaine on pathologic retinal neovascularization via suppression of reactive oxygen species mediated vascular endothelial growth factor signaling. Vascular Pharmacology. 2017; 90: 19-26. doi: 10.1016/j.vph.2016.07.007
96. Ejaz A, Martinez-Guino L, Goldfine AB, et al. Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice. Diabetes. 2016; 65(4): 902-912. doi: 10.2337/db15-1094
97. Kanbak G, Akyüz F, İnal M. Preventive effect of betaine on ethanol-induced membrane lipid composition and membrane ATPases. Archives of Toxicology. 2001; 75(1): 59-61. doi: 10.1007/s002040000179
98. Ghyczy M, Boros M. Electrophilic methyl groups present in the diet ameliorate pathological states induced by reductive and oxidative stress: a hypothesis. British Journal of Nutrition. 2001; 85(4): 409-414. doi: 10.1079/bjn2000274
99. Kim SK, Kim YC. Effects of betaine supplementation on hepatic metabolism of sulfur-containing amino acids in mice. Journal of Hepatology. 2005; 42(6): 907-913. doi: 10.1016/j.jhep.2005.01.017
100. Waisberg M, Joseph P, Hale B, et al. Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology. 2003; 192(2-3): 95-117. doi: 10.1016/S0300-483X (03)00305-6
101. Fouad AA, Jresat I. Protective effect of telmisartan against cadmium-induced nephrotoxicity in mice. Life Sciences. 2011; 89(1-2): 29-35. doi: 10.1016/j.lfs.2011.04.019
102. Huang Y, Shih C, Huang C, et al. Effects of cadmium on structure and enzymatic activity of Cu, Zn‐SOD and oxidative status in neural cells. Journal of Cellular Biochemistry. 2006; 98(3): 577-589. doi: 10.1002/jcb.20772
103. Chance B, Greenstein D, Roughton F. The mechanism of catalase action. I. Steady-state analysis. Archives of Biochemistry and Biophysics. 1952; 37(2): 301-321. doi: 10.1016/0003-9861(52)90194-X
104. Meister A, Anderson ME. Glutathione. Annual Review of Biochemistry. 1983; 52(1): 711-760. doi: 10.1146/annurev.bi.52.070183.003431
105. Sunitha S, Nagaraj M, Varalakshmi P. Hepatoprotective effect of lupeol and lupeol linoleate on tissue antioxidant defence system in cadmium-induced hepatotoxicity in rats. Fitoterapia. 2001; 72(5): 516-523. doi: 10.1016/S0367-326X (01)00259-3
106. Gambhir J, Nath R. Effect of cadmium on tissue glutathione and glutathione peroxidase in rats: influence of selenium supplementation. Indian journal of experimental biology. 1992; 30(7): 597-601.
107. Chen L, Chen Y, Wang L, et al. Higher homocysteine and lower betaine increase the risk of microangiopathy in patients with diabetes mellitus carrying the GG genotype of PEMT G774C. Diabetes/Metabolism Research and Reviews. 2013; 29(8): 607-617. doi: 10.1002/dmrr.2432
108. Sun J, Wen S, Zhou J, et al. Association between malnutrition and hyperhomocysteine in Alzheimer’s disease patients and diet intervention of betaine. Journal of Clinical Laboratory Analysis. 2016; 31(5): e22090. doi: 10.1002/jcla.22090
109. Kunisawa K, Kido K, Nakashima N, et al. Betaine attenuates memory impairment after water-immersion restraint stress and is regulated by the GABAergic neuronal system in the hippocampus. European Journal of Pharmacology. 2017; 796: 122-130. doi: 10.1016/j.ejphar.2016.12.007
110. Di Pierro F, Orsi R, Settembre R. Role of betaine in improving the antidepressant effect of S-adenosyl-methionine in patients with mild-to-moderate depression. Journal of Multidisciplinary Healthcare. 2015; 39. doi: 10.2147/jmdh.s77766
111. Knight LS, Piibe Q, Lambie I, et al. Betaine in the Brain: Characterization of Betaine Uptake, its Influence on Other Osmolytes and its Potential Role in Neuroprotection from Osmotic Stress. Neurochemical Research. 2017; 42(12): 3490-3503. doi: 10.1007/s11064-017-2397-3
112. Roe AJ, Zhang S, Bhadelia RA, et al. Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults. The American Journal of Clinical Nutrition. 2017; 105(6): 1283-1290. doi: 10.3945/ajcn.116.137158
113. Guéant-Rodriguez RM, Spada R, Moreno-Garcia M, et al. Homocysteine is a determinant of ApoA-I and both are associated with ankle brachial index, in an Ambulatory Elderly Population. Atherosclerosis. 2011; 214(2): 480-485. doi: 10.1016/j.atherosclerosis.2010.11.031
114. Jiang H, Stabler SP, Allen RH, et al. Altered expression of apoA-I, apoA-IV and PON-1 activity in CBS deficient homocystinuria in the presence and absence of treatment: Possible implications for cardiovascular outcomes. Molecular Genetics and Metabolism. 2012; 107(1-2): 55-65. doi: 10.1016/j.ymgme.2012.04.025
115. Nemmar A, Yuvaraju P, Beegam S, et al. Betaine (N, N, N-trimethylglycine) averts photochemically-induced thrombosis in pial microvesselsin vivoand platelet aggregationin vitro. Experimental Biology and Medicine. 2015; 240(7): 955-960. doi: 10.1177/1535370214564749
116. Rosas-Rodríguez JA, Soñanez-Organis JG, Godoy-Lugo JA, et al. Betaine Aldehyde Dehydrogenase expression during physiological cardiac hypertrophy induced by pregnancy. Biochemical and Biophysical Research Communications. 2017; 490(3): 623-628. doi: 10.1016/j.bbrc.2017.06.087
117. Rehman A, Mehta KJ. Betaine in ameliorating alcohol-induced hepatic steatosis. European Journal of Nutrition. 2021; 61(3): 1167-1176. doi: 10.1007/s00394-021-02738-2
118. Wang C, Ma C, Gong L, et al. Preventive and therapeutic role of betaine in liver disease: A review on molecular mechanisms. European Journal of Pharmacology. 2021; 912: 174604. doi: 10.1016/j.ejphar.2021.174604
119. Pekkinen J, Olli K, Huotari A, et al. Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach. Molecular Nutrition & Food Research. 2013; 57(11): 1959-1968. doi: 10.1002/mnfr.201300142
120. Airaksinen K, Jokkala J, Ahonen I, et al. High‐Fat Diet, Betaine, and Polydextrose Induce Changes in Adipose Tissue Inflammation and Metabolism in C57BL/6J Mice. Molecular Nutrition & Food Research. 2018; 62(23). doi: 10.1002/mnfr.201800455
121. Jung G, Won SB, Kim J, et al. Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice. Toxicol Res. 2013; 29(1): 7-14. doi: 10.5487/TR.2013.29.1.007
122. Wang LJ, Zhang HW, Zhou JY, et al. Betaine attenuates hepatic steatosis by reducing methylation of the MTTP promoter and elevating genomic methylation in mice fed a high-fat diet. The Journal of Nutritional Biochemistry. 2014; 25(3): 329-336. doi: 10.1016/j.jnutbio.2013.11.007
123. Šišková K, Dubničková M, Pašková Ľ, et al. Betaine Increases the Butyrylcholinesterase Activity in Rat Plasma. Physiological Research. 2016; 101-108. doi: 10.33549/physiolres.933028
124. Xu L, Huang D, Hu Q, et al. Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet. British Journal of Nutrition. 2015; 113(12): 1835-1843. doi: 10.1017/s0007114515001130
125. Ge CX, Yu R, Xu MX, et al. Betaine prevented fructose-induced NAFLD by regulating LXRα/PPARα pathway and alleviating ER stress in rats. European Journal of Pharmacology. 2016; 770: 154-164. doi: 10.1016/j.ejphar.2015.11.043
126. Song Z, Deaciuc I, Zhou Z, et al. Involvement of AMP-activated protein kinase in beneficial effects of betaine on high-sucrose diet-induced hepatic steatosis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2007; 293(4): G894-G902. doi: 10.1152/ajpgi.00133.2007
127. Jung GY, Won SB, Kim J, et al. Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice. Toxicological Research. 2013; 29(1): 7-14. doi: 10.5487/tr.2013.29.1.007
128. Szkudelski T, Dłużewicz K, Sadoch J, et al. Effects of the activation of heme oxygenase-1 on hormonal and metabolic changes in rats fed a high-fat diet. Biomedicine & Pharmacotherapy. 2017; 87: 375-380. doi: 10.1016/j.biopha.2016.12.060
129. Hirsch GE, Heck TG. Inflammation, oxidative stress and altered heat shock response in type 2 diabetes: the basis for new pharmacological and non-pharmacological interventions. Archives of Physiology and Biochemistry. 2019; 128(2): 411-425. doi: 10.1080/13813455.2019.1687522
130. Gross DN, van den Heuvel APJ, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008; 27(16): 2320-2336. doi: 10.1038/onc.2008.25
131. Kathirvel E, Morgan K, Nandgiri G, et al. Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2010; 299(5): G1068-G1077. doi: 10.1152/ajpgi.00249.2010
132. Kim DH, Kim SM, Lee B, et al. Effect of betaine on hepatic insulin resistance through FOXO1-induced NLRP3 inflammasome. The Journal of Nutritional Biochemistry. 2017; 45: 104-114. doi: 10.1016/j.jnutbio.2017.04.014
133. Deminice R, da Silva RP, Lamarre SG, et al. Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism. Amino Acids. 2015; 47(4): 839-846. doi: 10.1007/s00726-014-1913-x
134. Szkudelska K, Chan MH, Okulicz M, et al. Betaine supplementation to rats alleviates disturbances induced by high-fat diet: Pleiotropic effects in model of type 2 diabetes. J Physiol Pharmacol. 2021; 72: 763-775.
135. Wang Z, Yao T, Pini M, et al. Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2010; 298(5): G634-G642. doi: 10.1152/ajpgi.00249.2009
136. Ziolkowska S, Binienda A, Jabłkowski M, et al. The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease. International Journal of Molecular Sciences. 2021; 22(20): 11128. doi: 10.3390/ijms222011128
137. Zheng J, Xiao H, Duan Y, et al. Roles of amino acid derivatives in the regulation of obesity. Food & Function. 2021; 12(14): 6214-6225. doi: 10.1039/d1fo00780g
138. Dai X, Liu S, Cheng L, et al. Betaine Supplementation Attenuates S-Adenosylhomocysteine Hydrolase-Deficiency-Accelerated Atherosclerosis in Apolipoprotein E-Deficient Mice. Nutrients. 2022; 14(3): 718. doi: 10.3390/nu14030718
139. Gonzalez LL, Garrie K, Turner MD. Type 2 diabetes—An autoinflammatory disease driven by metabolic stress. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease. 2018; 1864(11): 3805-3823. doi: 10.1016/j.bbadis.2018.08.034
140. Kuryłowicz A, Koźniewski K. Anti-Inflammatory Strategies Targeting Metaflammation in Type 2 Diabetes. Molecules. 2020; 25(9): 2224. doi: 10.3390/molecules25092224
141. Huang X, Yang Z. Resistin’s, obesity and insulin resistance: the continuing disconnect between rodents and humans. Journal of Endocrinological Investigation. 2015; 39(6): 607-615. doi: 10.1007/s40618-015-0408-2
142. Fan CY, Wang MX, Ge CX, et al. Betaine supplementation protects against high-fructose-induced renal injury in rats. The Journal of Nutritional Biochemistry. 2014; 25(3): 353-362. doi: 10.1016/j.jnutbio.2013.11.010
143. Frühbeck G, Méndez-Giménez L, Fernández-Formoso JA, et al. Regulation of adipocyte lipolysis. Nutrition Research Reviews. 2014; 27(1): 63-93. doi: 10.1017/s095442241400002x
144. Barchetta I, Cimini FA, Ciccarelli G, et al. Sick fat: the good and the bad of old and new circulating markers of adipose tissue inflammation. Journal of Endocrinological Investigation. 2019; 42(11): 1257-1272. doi: 10.1007/s40618-019-01052-3
145. Liang W, Ye D. The potential of adipokines as biomarkers and therapeutic agents for vascular complications in type 2 diabetes mellitus. Cytokine & Growth Factor Reviews. 2019; 48: 32-39. doi: 10.1016/j.cytogfr.2019.06.002
146. Dilworth L, Facey A, Omoruyi F. Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues. International Journal of Molecular Sciences. 2021; 22(14): 7644. doi: 10.3390/ijms22147644
147. Jang A, Kim D, Sung KS, et al. The effect of dietary α-lipoic acid, betaine,l-carnitine, and swimming on the obesity of mice induced by a high-fat diet. Food Funct. 2014; 5(8): 1966-1974. doi: 10.1039/c4fo00246f
148. Du J, Shen L, Tan Z, et al. Betaine Supplementation Enhances Lipid Metabolism and Improves Insulin Resistance in Mice Fed a High-Fat Diet. Nutrients. 2018; 10(2): 131. doi: 10.3390/nu10020131
149. Zhou X, Chen J, Chen J, et al. The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase α1 subunit. The Journal of Nutritional Biochemistry. 2015; 26(12): 1678-1684. doi: 10.1016/j.jnutbio.2015.08.014
150. Fawcett KA, Barroso I. The genetics of obesity: FTO leads the way. Trends in Genetics. 2010; 26(6): 266-274. doi: 10.1016/j.tig.2010.02.006
151. Villalobos-Labra R, Subiabre M, Toledo F, et al. Endoplasmic reticulum stress and development of insulin resistance in adipose, skeletal, liver, and foetoplacental tissue in diabesity. Molecular Aspects of Medicine. 2019; 66: 49-61. doi: 10.1016/j.mam.2018.11.001
152. Ejaz A, Martinez-Guino L, Goldfine AB, et al. Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice. Diabetes. 2016; 65(4): 902-912. doi: 10.2337/db15-1094
153. Sobczak AIS, Blindauer CA, Stewart AJ. Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes. Nutrients. 2019; 11(9): 2022. doi: 10.3390/nu11092022
154. Blaak EE. Metabolic fluxes in skeletal muscle in relation to obesity and insulin resistance. Best Practice & Research Clinical Endocrinology & Metabolism. 2005; 19(3): 391-403. doi: 10.1016/j.beem.2005.04.001
155. Gemmink A, Goodpaster BH, Schrauwen P, et al. Intramyocellular lipid droplets and insulin sensitivity, the human perspective. Biochimica et Biophysica Acta (BBA)—Molecular and Cell Biology of Lipids. 2017; 1862(10): 1242-1249. doi: 10.1016/j.bbalip.2017.07.010
156. Wu H, Ballantyne CM. Skeletal muscle inflammation and insulin resistance in obesity. Journal of Clinical Investigation. 2017; 127(1): 43-54. doi: 10.1172/jci88880
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