EFFECT OF HYPERHOMOCYSTEINEMIA ON BLOOD GLUCOSE HOMEOSTASIS

DING Tian-qi; CHEN Jian; WEN Bo; CHU Wen-bin; FAN Rong; CHEN Xue-wei

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (1) : 22-27.

ORIGINAL ARTICLES

DING Tian-qi¹, CHEN Jian¹, WEN Bo¹, CHU Wen-bin¹, FAN Rong^1,2, CHEN Xue-wei¹

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Abstract

Objective To explore the effects of hyperhomocysteinemia (HHcy) on blood glucose homeostasis. Methods C57BL / 6 mice were randomly divided into two groups: control group (CHOW) and model group (HMD), 10 mice per group. The CHOW group was fed the AIN-93G diet, and the HMD group fed the AIN-93G+2% methionine diet. The oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and insulin secretion experiment were performed. The morphological changes in the pancreas were observed by hematoxylin-eosin (HE) staining, pancreatic insulin expression by immunofluorescence staining, and total pancreatic insulin content by enzyme-linked immunosorbent assay (ELISA). Results Compared with the CHOW group, after 1 month of feeding, plasma Hcy was significantly increased in the HMD group (P<0.0001). After 4 months of feeding, there was no significant difference in fasting blood glucose between the two groups, but mice in the HMD group had significantly increased random blood glucose (P<0.0001), impaired glucose tolerance (P<0.001) and insulin tolerance (P<0.001); Compared with the CHOW group, the glucose-stimulated insulin secretion was reduced in the HMD group (P<0.0001). The results of HE staining showed that there was no significant change in the pancreatic morphology between the two groups. Immunofluorescence chemical analysis revealed enhanced insulin fluorescence intensity in the pancreas of the HMD group (P<0.001). Compared with the CHOW group, the total pancreatic insulin content increased significantly in the HMD group. The difference was statistically significant (P<0.0001). Conclusion HHcy can cause the development of type 2 diabetes mellitus (T2DM), and homocysteine may affect blood glucose homeostasis by damaging insulin secretion function.

Key words

Hcy / HHcy / blood glucose homeostasis / pancreatic β-cells / insulin secretion

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DING Tian-qi, CHEN Jian, WEN Bo, CHU Wen-bin, FAN Rong, CHEN Xue-wei. EFFECT OF HYPERHOMOCYSTEINEMIA ON BLOOD GLUCOSE HOMEOSTASIS[J]. Acta Nutrimenta Sinica. 2024, 46(1): 22-27

References

[1] Brustolin S, Giugliani R, Félix TM.Genetics of homocysteine metabolism and associated disorders[J]. Braz J Med Biol Res, 2010, 43:1–7.
[2] Zaric BL, Obradovic M, Bajic V, et al. Homocysteine and hyperhomocysteinaemia[J]. Curr Med Chem, 2019, 26:2948–2961.
[3] Maron BA, Loscalzo J.Homocysteine[J]. Clin Lab Med, 2006, 26:591–609.
[4] Galicia-Garcia U, Benito-Vicente A, Jebari S, et al. Pathophysiology of type 2 diabetes mellitus[J]. Int J Mol Sci, 2020, 21: 6275–6309.
[5] Ala OA, Akintunde AA, Ikem RT, et al. Association between insulin resistance and total plasma homocysteine levels in type 2 diabetes mellitus patients in south west Nigeria[J]. Diabetes Metab Syndr, 2017, 11: S803–S809.
[6] Joshi MB, Baipadithaya G, Balakrishnan A, et al. Elevated homocysteine levels in type 2 diabetes induce constitutive neutrophil extracellular traps[J]. Sci Rep, 2016, 6: 36362–36377.
[7] 王越, 张雄. 高同型半胱氨酸血症与2型糖尿病相互影响机制的研究进展[J].内蒙古医学杂志, 2022, 54: 1498–1502.
[8] Luo WM, Zhang ZP, Zhang W, et al. The association of homocysteine and diabetic retinopathy in homocysteine cycle in Chinese patients with type 2 diabetes[J]. Front Endocrinol (Lausanne), 2022, 13: 883845–883856.
[9] González R, Pedro T, Martinez-Hervas S, et al. Plasma homocysteine levels are independently associated with the severity of peripheral polyneuropathy in type 2 diabetic subjects[J]. J Peripher Nerv Syst, 2012, 17: 191–6.
[10] Wang T, Wang Q, Wang Z, et al. Diagnostic value of the combined measurement of serum Hcy, serum Cys C, and urinary microalbumin in type 2 diabetes mellitus with early complicating diabetic nephropathy[J].ISRN Endocrinol, 2013, 2013: 407452–407458.
[11] Jan M, Cueto R, Jiang X, et al. Molecular processes mediating hyperhomocysteinemia-induced metabolic reprogramming, redox regulation and growth inhibition in endothelial cells[J]. Redox Biol, 2021, 45: 102018–102036.
[12] Lee SH, Park SY, Choi CS.Insulin resistance: from mechanisms to therapeutic strategies[J]. Diabetes Metab J, 2022, 46: 15–37.
[13] Zhang X, Qu YY, Liu L, et al. Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation[J]. Cell Rep, 2021, 37: 109821–109840.
[14] Li Y, Zhang H, Jiang C, et al. Hyperhomocysteinemia promotes insulin resistance by inducing endoplasmic reticulum stress in adipose tissue[J]. J Biol Chem, 2013, 288: 9583–9592.
[15] Rachdaoui N.Insulin: The friend and the foe in the development of type 2 diabetes mellitus[J]. Int J Mol Sci, 2020, 21: 1770–1791.
[16] 储文彬, 丁天琪, 文波, 等. 氢对高蛋氨酸饮食诱导的高同型半胱氨酸血症和脂肪肝的缓解作用[J]. 中国应用生理学杂志, 2022, 38: 787–793.
[17] DeFronzo RA, Ferrannini E, Groop L, et al. Type 2 diabetes mellitus[J]. Nat Rev Dis Primers, 2015, 1:15019–15019.
[18] Jang C, Oh SF, Wada S, et al. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance[J]. Nat Med, 2016, 22: 421–6.
[19] Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes[J]. Nat Med, 2011, 17: 448–53.
[20] Cheng CK, Wang C, Shang W, et al. A high methionine and low folate diet alters glucose homeostasis and gut microbiome[J]. Biochem Biophys Rep, 2021, 25: 100921–100928.
[21] Cueto R, Zhang L, Shan HM, et al. Identification of homocysteine-suppressive mitochondrial ETC complex genes and tissue expression profile-Novel hypothesis establishment[J]. Redox Biol, 2018, 17: 70–88.
[22] Zhang SY, Dong YQ, Wang P, et al. Adipocyte-derived lysophosphatidylcholine activates adipocyte and adipose tissue macrophage nod-like receptor protein 3 inflammasomes mediating homocysteine-induced insulin resistance[J]. EBioMedicine, 2018, 31: 202–216.
[23] Huang T, Ren J, Huang J, et al. Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach[J]. BMC Genomics, 2013, 14: 867–878.