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Review Open Access

Role of ceramides in diabetic foot ulcers (Review)

  • Authors:
    • Ying Wang
    • Zhen Sun
    • Guangyao Zang
    • Lili Zhang
    • Zhongqun Wang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 26
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    Published online on: February 6, 2023
       https://doi.org/10.3892/ijmm.2023.5229
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Abstract

Diabetes mellitus (DM) is a metabolic disorder, which if not managed properly, can lead to serious health problems over time and impose significant financial burden on the patient, their family and society as a whole. The study of this disease and the underlying biological mechanism is gaining momentum. Multiple pieces of conclusive evidence show that ceramides are involved in the occurrence and development of diabetes. The present review focuses on the function of ceramides, a type of sphingolipid signaling molecule, to provide a brief description of ceramides and their metabolism, discuss the significant roles of ceramides in the healthy skin barrier, and speculate on the potential involvement of ceramides in the pathogenesis and development of diabetic foot ulcers (DFUs). Understanding these aspects of this disease more thoroughly is crucial to establish how ceramides contribute to the etiology of diabetic foot infections and identify possible therapeutic targets for the treatment of DFUs.
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1 

Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H and Martín C: Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 21:62752020. View Article : Google Scholar : PubMed/NCBI

2 

Zheng Y, Ley SH and Hu FB: Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 14:88–98. 2018. View Article : Google Scholar

3 

Demir S, Nawroth PP, Herzig S and Ekim Üstünel B: Emerging targets in type 2 diabetes and diabetic complications. Adv Sci (Weinh). 8:21002752021. View Article : Google Scholar : PubMed/NCBI

4 

Everett E and Mathioudakis N: Update on management of diabetic foot ulcers:. Ann N Y Acad Sci. 1411:153–165. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Wolf SJ, Melvin WJ and Gallagher K: Macrophage-mediated inflammation in diabetic wound repair. Semin Cell Dev Biol. 119:111–118. 2021. View Article : Google Scholar : PubMed/NCBI

6 

Gomez-Larrauri A, Presa N, Dominguez-Herrera A, Ouro A, Trueba M and Gomez-Muñoz A: Role of bioactive sphingolipids in physiology and pathology. Essays Biochem. 64:579–589. 2020. View Article : Google Scholar : PubMed/NCBI

7 

Castro BM, Prieto M and Silva LC: Ceramide: A simple sphingolipid with unique biophysical properties. Prog Lipid Res. 54:53–67. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Summers SA: Editorial: The role of ceramides in diabetes and cardiovascular disease. Front Endocrinol (Lausanne). 12:6678852021. View Article : Google Scholar : PubMed/NCBI

9 

Raichur S, Brunner B, Bielohuby M, Hansen G, Pfenninger A, Wang B, Bruning JC, Larsen PJ and Tennagels N: The role of C16:0 ceramide in the development of obesity and type 2 diabetes: CerS6 inhibition as a novel therapeutic approach. Mol Metab. 21:36–50. 2019. View Article : Google Scholar : PubMed/NCBI

10 

Field BC, Gordillo R and Scherer PE: The role of ceramides in diabetes and cardiovascular disease regulation of ceramides by adipokines. Front Endocrinol (Lausanne). 11:5692502020. View Article : Google Scholar : PubMed/NCBI

11 

Lechner A, Akdeniz M, Tomova-Simitchieva T, Bobbert T, Moga A, Lachmann N, Blume-Peytavi U and Kottner J: Comparing skin characteristics and molecular markers of xerotic foot skin between diabetic and non-diabetic subjects: An exploratory study. J Tissue Viability. 28:200–209. 2019. View Article : Google Scholar : PubMed/NCBI

12 

Summers SA, Chaurasia B and Holland WL: Metabolic messengers: Ceramides. Nat Metab. 1:1051–1058. 2019. View Article : Google Scholar

13 

Custodia A, Aramburu-Núñez M, Correa-Paz C, Posado-Fernández A, Gómez-Larrauri A, Castillo J, Gómez-Muñoz A, Sobrino T and Ouro A: Ceramide metabolism and Parkinson's disease-therapeutic targets. Biomolecules. 11:9452021. View Article : Google Scholar : PubMed/NCBI

14 

Alexandropoulou I, Grammatikopoulou MG, Gkouskou KK, Pritsa AA, Vassilakou T, Rigopoulou E, Lindqvist HM and Bogdanos DP: Ceramides in autoimmune rheumatic diseases: Existing evidence and therapeutic considerations for diet as an anticeramide treatment. Nutrients. 15:2292023. View Article : Google Scholar : PubMed/NCBI

15 

Mandell EW and Savani RC: Ceramides, autophagy, and apoptosis mechanisms of ventilator-induced lung injury and potential therapeutic targets. Am J Respir Crit Care Med. 199:687–689. 2019. View Article : Google Scholar :

16 

Pal P, Atilla-Gokcumen GE and Frasor J: Emerging roles of ceramides in breast cancer biology and therapy. Int J Mol Sci. 23:111782022. View Article : Google Scholar : PubMed/NCBI

17 

Wattenberg BW: The long and the short of ceramides. J Biol Chem. 293:9922–9923. 2018. View Article : Google Scholar : PubMed/NCBI

18 

Cha HJ, He C, Zhao H, Dong Y, An IS and An S: Intercellular and intracellular functions of ceramides and their metabolites in skin (Review). Int J Mol Med. 38:16–22. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Magnan C and Le Stunff H: Role of hypothalamic de novo ceramides synthesis in obesity and associated metabolic disorders. Mol Metab. 53:1012982021. View Article : Google Scholar : PubMed/NCBI

20 

Insausti-Urkia N, Solsona-Vilarrasa E, Garcia-Ruiz C and Fernandez-Checa JC: Sphingomyelinases and liver diseases. Biomolecules. 10:14972020. View Article : Google Scholar : PubMed/NCBI

21 

Taniguchi M and Okazaki T: Role of ceramide/sphingomyelin (SM) balance regulated through 'SM cycle' in cancer. Cell Signal. 87:1101192021. View Article : Google Scholar

22 

Hammerschmidt P and Brüning JC: Contribution of specific ceramides to obesity-associated metabolic diseases. Cell Mol Life Sci. 79:3952022. View Article : Google Scholar : PubMed/NCBI

23 

Bhattacharya N, Sato WJ, Kelly A, Ganguli-Indra G and Indra AK: Epidermal lipids: Key mediators of atopic dermatitis pathogenesis. Trends Mol Med. 25:551–562. 2019. View Article : Google Scholar : PubMed/NCBI

24 

Roszczyc-Owsiejczuk K and Zabielski P: Sphingolipids as a culprit of mitochondrial dysfunction in insulin resistance and type 2 diabetes. Front Endocrinol (Lausanne). 12:6351752021. View Article : Google Scholar : PubMed/NCBI

25 

Aldoghachi AF, Baharudin A, Ahmad U, Chan SC, Ong TA, Yunus R, Razack AH, Yusoff K and Veerakumarasivam A: Evaluation of CERS2 gene as a potential biomarker for bladder cancer. Dis Markers. 2019:38751472019. View Article : Google Scholar : PubMed/NCBI

26 

Polubothu S, Glover M, Holder SE and Kinsler VA: Uniparental disomy as a mechanism for CERS3-mutated autosomal recessive congenital ichthyosis. Br J Dermatol. 179:1214–1215. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Sheridan M and Ogretmen B: The role of ceramide metabolism and signaling in the regulation of mitophagy and cancer therapy. Cancers (Basel). 13:24752021. View Article : Google Scholar : PubMed/NCBI

28 

Kurz J, Parnham MJ, Geisslinger G and Schiffmann S: Ceramides as novel disease biomarkers. Trends Mol Med. 25:20–32. 2019. View Article : Google Scholar

29 

Mullen TD, Hannun YA and Obeid LM: Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J. 441:789–802. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Parveen F, Bender D, Law SH, Mishra VK, Chen CC and Ke LY: Role of ceramidases in sphingolipid metabolism and human diseases. Cells. 8:15732019. View Article : Google Scholar : PubMed/NCBI

31 

Li Q, Fang H, Dang E and Wang G: The role of ceramides in skin homeostasis and inflammatory skin diseases. J Dermatol Sci. 97:2–8. 2020. View Article : Google Scholar

32 

Jung K, Kim SH, Joo KM, Lim SH, Shin JH, Roh J, Kim E, Park W and Kim W: Oral intake of enzymatically decomposed AP collagen peptides improves skin moisture and ceramide and natural moisturizing factor contents in the stratum corneum. Nutrients. 13:43722021. View Article : Google Scholar : PubMed/NCBI

33 

Ramírez-Vélez R, Martínez-Velilla N, Correa-Rodríguez M, Sáez de Asteasu ML, Zambom-Ferraresi F, Palomino-Echeverria S, García-Hermoso A and Izquierdo M: Lipidomic signatures from physically frail and robust older adults at hospital admission. Geroscience. 44:1677–1688. 2022. View Article : Google Scholar : PubMed/NCBI

34 

Coderch L, López O, de la Maza A and Parra JL: Ceramides and skin function. Am J Clin Dermatol. 4:107–129. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Badhe Y, Gupta R and Rai B: Structural and barrier properties of the skin ceramide lipid bilayer: A molecular dynamics simulation study. J Mol Model. 25:1402019. View Article : Google Scholar : PubMed/NCBI

36 

Vollmer DL, West VA and Lephart ED: Enhancing skin health: By oral administration of natural compounds and minerals with implications to the dermal microbiome. Int J Mol Sci. 19:30592018. View Article : Google Scholar : PubMed/NCBI

37 

Kim B, Shon JC, Seo HS, Liu KH, Lee JW, Ahn SK and Hong SP: Decrease of ceramides with long-chain fatty acids in psoriasis: Possible inhibitory effect of interferon gamma on chain elongation. Exp Dermatol. 31:122–132. 2022. View Article : Google Scholar

38 

Wang L, Liu M, Ning D, Zhu H, Shan G, Wang D, Ping B, Yu Y, Yang H, Yan K, et al: Low serum ZAG levels correlate with determinants of the metabolic syndrome in Chinese subjects. Front Endocrinol (Lausanne). 11:1542020. View Article : Google Scholar : PubMed/NCBI

39 

Fujiwara A, Morifuji M, Kitade M, Kawahata K, Fukasawa T, Yamaji T, Itoh H and Kawashima M: Age-related and seasonal changes in covalently bound ceramide content in forearm stratum corneum of Japanese subjects: Determination of molecular species of ceramides. Arch Dermatol Res. 310:729–735. 2018. View Article : Google Scholar : PubMed/NCBI

40 

Łuczaj W, Jastrząb A, do Rosário Domingues M, Domingues P and Skrzydlewska E: Changes in phospholipid/ceramide profiles and eicosanoid levels in the plasma of rats irradiated with UV rays and treated topically with cannabidiol. Int J Mol Sci. 22:87002021. View Article : Google Scholar : PubMed/NCBI

41 

Fujii M: The pathogenic and therapeutic implications of ceramide abnormalities in atopic dermatitis. Cells. 10:23862021. View Article : Google Scholar : PubMed/NCBI

42 

Meckfessel MH and Brandt S: The structure, function, and importance of ceramides in skin and their use as therapeutic agents in skin-care products. J Am Acad Dermatol. 71:177–184. 2014. View Article : Google Scholar : PubMed/NCBI

43 

Draelos ZD: The science behind skin care: Moisturizers. J Cosmet Dermatol. 17:138–144. 2018. View Article : Google Scholar : PubMed/NCBI

44 

Wertz PW: Roles of lipids in the permeability barriers of skin and oral mucosa. Int J Mol Sci. 22:52292021. View Article : Google Scholar : PubMed/NCBI

45 

Bocheńska K and Gabig-Cimińska M: Unbalanced sphingolipid metabolism and its implications for the pathogenesis of psoriasis. Molecules. 25:11302020. View Article : Google Scholar

46 

Santinha DR, Marques DR, Maciel EA, Simões CS, Rosa S, Neves BM, Macedo B, Domingues P, Cruz MT and Domingues MR: Profiling changes triggered during maturation of dendritic cells: A lipidomic approach. Anal Bioanal Chem. 403:457–471. 2012. View Article : Google Scholar : PubMed/NCBI

47 

Paget C, Deng S, Soulard D, Priestman DA, Speca S, von Gerichten J, Speak AO, Saroha A, Pewzner-Jung Y, Futerman AH, et al: TLR9-mediated dendritic cell activation uncovers mammalian ganglioside species with specific ceramide backbones that activate invariant natural killer T cells. PLoS Biol. 17:e30001692019. View Article : Google Scholar : PubMed/NCBI

48 

Scheiblich H, Schlütter A, Golenbock DT, Latz E, Martinez-Martinez P and Heneka MT: Activation of the NLRP3 inflammasome in microglia: The role of ceramide. J Neurochem. 143:534–550. 2017. View Article : Google Scholar : PubMed/NCBI

49 

Zheng Y, Hunt RL, Villaruz AE, Fisher EL, Liu R, Liu Q, Cheung GYC, Li M and Otto M: Commensal staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides. Cell Host Microbe. 30:301–313.e9. 2022. View Article : Google Scholar : PubMed/NCBI

50 

Wang Y, Shao T, Wang J, Huang X, Deng X, Cao Y, Zhou M and Zhao C: An update on potential biomarkers for diagnosing diabetic foot ulcer at early stage. Biomed Pharmacother. 133:1109912021. View Article : Google Scholar

51 

Abbott CA, Chatwin KE, Foden P, Hasan AN, Sange C, Rajbhandari SM, Reddy PN, Vileikyte L, Bowling FL, Boulton AJM and Reeves ND: Innovative intelligent insole system reduces diabetic foot ulcer recurrence at plantar sites: A prospective, randomised, proof-of-concept study. Lancet Digit Health. 1:e308–e318. 2019. View Article : Google Scholar : PubMed/NCBI

52 

Kim EJ and Han K: Factors related to self-care behaviours among patients with diabetic foot ulcers. J Clin Nurs. 29:1712–1722. 2020. View Article : Google Scholar : PubMed/NCBI

53 

Bandyk DF: The diabetic foot: Pathophysiology, evaluation, and treatment. Semin Vasc Surg. 31:43–48. 2018. View Article : Google Scholar : PubMed/NCBI

54 

Aldana PC, Cartron AM and Khachemoune A: Reappraising diabetic foot ulcers: A focus on mechanisms of ulceration and clinical evaluation. Int J Low Extrem Wounds. 21:294–302. 2022. View Article : Google Scholar

55 

Rubitschung K, Sherwood A, Crisologo AP, Bhavan K, Haley RW, Wukich DK, Castellino L, Hwang H, La Fontaine J, Chhabra A, et al: Pathophysiology and molecular imaging of diabetic foot infections. Int J Mol Sci. 22:115522021. View Article : Google Scholar : PubMed/NCBI

56 

Armstrong DG, Boulton AJM and Bus SA: Diabetic foot ulcers and their recurrence. N Engl J Med. 376:2367–2375. 2017. View Article : Google Scholar : PubMed/NCBI

57 

Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, Bril V, Russell JW and Viswanathan V: Diabetic neuropathy. Nat Rev Dis Primers. 5:422019. View Article : Google Scholar : PubMed/NCBI

58 

Volpe CMO, Villar-Delfino PH, dos Anjos PMF and Nogueira-Machado JA: Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 9:1192018. View Article : Google Scholar : PubMed/NCBI

59 

Bönhof GJ, Herder C, Strom A, Papanas N, Roden M and Ziegler D: Emerging biomarkers, tools, and treatments for diabetic polyneuropathy. Endocr Rev. 40:153–192. 2019. View Article : Google Scholar

60 

Hammad SM, Baker NL, El Abiad JM, Spassieva SD, Pierce JS, Rembiesa B, Bielawski J, Lopes-Virella MF and Klein RL; DCCT/EDIC Group of Investigators: Increased plasma levels of select deoxy-ceramide and ceramide species are associated with increased odds of diabetic neuropathy in type 1 diabetes: A pilot study. Neuromolecular Med. 19:46–56. 2017. View Article : Google Scholar :

61 

Strain WD and Paldánius PM: Diabetes, cardiovascular disease and the microcirculation. Cardiovasc Diabetol. 17:572018. View Article : Google Scholar : PubMed/NCBI

62 

Criqui MH, Matsushita K, Aboyans V, Hess CN, Hicks CW, Kwan TW, McDermott MM, Misra S, Ujueta F; American Heart Association Council on Epidemiology and Prevention; et al: Lower extremity peripheral artery disease: Contemporary epidemiology, management gaps, and future directions: A scientific statement from the american heart association. Circulation. 144. pp. e171–e191. 2021, View Article : Google Scholar

63 

He X and Schuchman EH: Ceramide and ischemia/reperfusion injury. J Lipids. 2018:36467252018. View Article : Google Scholar : PubMed/NCBI

64 

Davis FM, Kimball A, Boniakowski A and Gallagher K: Dysfunctional wound healing in diabetic foot ulcers: New crossroads. Curr Diab Rep. 18:22018. View Article : Google Scholar : PubMed/NCBI

65 

Sloan G, Selvarajah D and Tesfaye S: Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy. Nat Rev Endocrinol. 17:400–420. 2021. View Article : Google Scholar : PubMed/NCBI

66 

Zweier JL and Ilangovan G: Regulation of nitric oxide metabolism and vascular tone by cytoglobin. Antioxid Redox Signal. 32:1172–1187. 2020. View Article : Google Scholar :

67 

Sun HJ, Wu ZY, Nie XW and Bian JS: Role of endothelial dysfunction in cardiovascular diseases: The link between inflammation and hydrogen sulfide. Front Pharmacol. 10:15682020. View Article : Google Scholar : PubMed/NCBI

68 

Chabowski DS, Cohen KE, Abu-Hatoum O, Gutterman DD and Freed JK: Crossing signals: Bioactive lipids in the microvasculature. Am J Physiol Heart Circ Physiol. 318:H1185–H1197. 2020. View Article : Google Scholar : PubMed/NCBI

69 

Zhang QJ, Holland WL, Wilson L, Tanner JM, Kearns D, Cahoon JM, Pettey D, Losee J, Duncan B, Gale D, et al: Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex. Diabetes. 61:1848–1859. 2012. View Article : Google Scholar : PubMed/NCBI

70 

Akawi N, Checa A, Antonopoulos AS, Akoumianakis I, Daskalaki E, Kotanidis CP, Kondo H, Lee K, Yesilyurt D, Badi I, et al: Fat-secreted ceramides regulate vascular redox state and influence outcomes in patients with cardiovascular disease. J Am Coll Cardiol. 77:2494–2513. 2021. View Article : Google Scholar : PubMed/NCBI

71 

Akhiyat N, Vasile V, Ahmad A, Sara JD, Nardi V, Lerman LO, Jaffe A and Lerman A: Plasma ceramide levels are elevated in patients with early coronary atherosclerosis and endothelial dysfunction. J Am Heart Assoc. 11:e0228522022. View Article : Google Scholar : PubMed/NCBI

72 

Karakashian AA, Giltiay NV, Smith GM and Nikolova-Karakashian MN: Expression of neutral sphingomyelinase-2 (NSMase-2) in primary rat hepatocytes modulates IL-beta-induced JNK activation. FASEB J. 18:968–970. 2004. View Article : Google Scholar : PubMed/NCBI

73 

Parker BA, Walton CM, Carr ST, Andrus JL, Cheung ECK, Duplisea MJ, Wilson EK, Draney C, Lathen DR, Kenner KB, et al: β-Hydroxybutyrate elicits favorable mitochondrial changes in skeletal muscle. Int J Mol Sci. 19:22472018. View Article : Google Scholar

74 

Cogolludo A, Villamor E, Perez-Vizcaino F and Moreno L: Ceramide and regulation of vascular tone. Int J Mol Sci. 20:4112019. View Article : Google Scholar : PubMed/NCBI

75 

Sletten AC, Peterson LR and Schaffer JE: Manifestations and mechanisms of myocardial lipotoxicity in obesity. J Intern Med. 284:478–491. 2018. View Article : Google Scholar : PubMed/NCBI

76 

Arsenault EJ, McGill CM and Barth BM: Sphingolipids as regulators of neuro-inflammation and NADPH oxidase 2. Neuromolecular Med. 23:25–46. 2021. View Article : Google Scholar : PubMed/NCBI

77 

Patwardhan GA, Beverly LJ and Siskind LJ: Sphingolipids and mitochondrial apoptosis. J Bioenerg Biomembr. 48:153–168. 2016. View Article : Google Scholar

78 

Colombini M: Ceramide channels and mitochondrial outer membrane permeability. J Bioenerg Biomembr. 49:57–64. 2017. View Article : Google Scholar

79 

Cantalupo A, Sasset L, Gargiulo A, Rubinelli L, Del Gaudio I, Benvenuto D, Wadsack C, Jiang XC, Bucci MR and Di Lorenzo A: Endothelial sphingolipid de novo synthesis controls blood pressure by regulating signal transduction and NO via ceramide. Hypertension. 75:1279–1288. 2020. View Article : Google Scholar : PubMed/NCBI

80 

Pérez-Villavicencio R, Flores-Estrada J, Franco M, Escalante B, Pérez-Méndez O, Mercado A and Bautista-Pérez R: Effect of empagliflozin on sphingolipid catabolism in diabetic and hypertensive rats. Int J Mol Sci. 23:28832022. View Article : Google Scholar : PubMed/NCBI

81 

Lin YH, Jewell BE, Gingold J, Lu L, Zhao R, Wang LL and Lee DF: Osteosarcoma: Molecular pathogenesis and iPSC modeling. Trends Mol Med. 23:737–755. 2017. View Article : Google Scholar : PubMed/NCBI

82 

Altura BM, Gebrewold A, Carella A, Shah NC, Shah GJ, Resnick LM and Altura BT: Why vasculitis probably can be ameliorated with magnesium and antagonists of ceramides and platelet-activating factor. MOJ Anat Physiol. 6:120–123. 2019.

83 

Borodzicz-Jażdżyk S, Jażdżyk P, Łysik W, Cudnoch-Jedrzejewska A and Czarzasta K: Sphingolipid metabolism and signaling in cardiovascular diseases. Front Cardiovasc Med. 9:9159612022. View Article : Google Scholar

84 

Zhang Y, Zhao H, Liu B, Shu H, Zhang L, Bao M, Yi W, Tan Y, Ji X, Zhang C, et al: Human serum metabolomic analysis reveals progression for high blood pressure in type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 9:e0023372021. View Article : Google Scholar : PubMed/NCBI

85 

Li X, Wang HF, Li XX and Xu M: Contribution of acid sphingomyelinase to angiotensin II-induced vascular adventitial remodeling via membrane rafts/Nox2 signal pathway. Life Sci. 219:303–310. 2019. View Article : Google Scholar : PubMed/NCBI

86 

Liu A, Chu YJ, Wang X, Yu R, Jiang H, Li Y, Zhou H, Gong LL, Yang WQ and Ju J: Serum metabolomics study based on LC-MS and antihypertensive effect of uncaria on spontaneously hypertensive rats. Evid Based Complement Alternat Med. 2018:92819462018. View Article : Google Scholar : PubMed/NCBI

87 

Shu H, Peng Y, Hang W, Li N, Zhou N and Wang DW: Emerging roles of ceramide in cardiovascular diseases. Aging Dis. 13:232–245. 2022. View Article : Google Scholar : PubMed/NCBI

88 

Choi SR, Lim JH, Kim MY, Kim EN, Kim Y, Choi BS, Kim YS, Kim HW, Lim KM, Kim MJ and Park CW: Adiponectin receptor agonist AdipoRon decreased ceramide, and lipotoxicity, and ameliorated diabetic nephropathy. Metabolism. 85:348–360. 2018. View Article : Google Scholar : PubMed/NCBI

89 

Yaribeygi H, Bo S, Ruscica M and Sahebkar A: Ceramides and diabetes mellitus: An update on the potential molecular relationships. Diabet Med. 37:11–19. 2020. View Article : Google Scholar

90 

Kane JP, Pullinger CR, Goldfine ID and Malloy MJ: Dyslipidemia and diabetes mellitus: Role of lipoprotein species and inter-related pathways of lipid metabolism in diabetes mellitus. Curr Opin Pharmacol. 61:21–27. 2021. View Article : Google Scholar : PubMed/NCBI

91 

Guitton J, Bandet CL, Mariko ML, Tan-Chen S, Bourron O, Benomar Y, Hajduch E and Le Stunff H: Sphingosine-1-phosphate metabolism in the regulation of obesity/type 2 diabetes. Cells. 9:16822020. View Article : Google Scholar : PubMed/NCBI

92 

Miller LG Jr, Young JA, Ray SK, Wang G, Purohit S, Banik NL and Dasgupta S: Sphingosine toxicity in EAE and MS: Evidence for ceramide generation via serine-palmitoyltransferase activation. Neurochem Res. 42:2755–2768. 2017. View Article : Google Scholar : PubMed/NCBI

93 

Siskind LJ: Mitochondrial ceramide and the induction of apoptosis. J Bioenerg Biomembr. 37:143–153. 2005. View Article : Google Scholar : PubMed/NCBI

94 

Mancini A, Imperlini E, Nigro E, Montagnese C, Daniele A, Orrù S and Buono P: Biological and nutritional properties of palm oil and palmitic acid: Effects on health. Molecules. 20:17339–17361. 2015. View Article : Google Scholar : PubMed/NCBI

95 

Park IB, Kim MH, Han JS and Park WJ: Gryllus bimaculatus extract protects against palmitate-induced β-cell death by inhibiting ceramide synthesis. Appl Biol Chem. 65:722022. View Article : Google Scholar

96 

Tong X, Chaudhry Z, Lee CC, Bone RN, Kanojia S, Maddatu J, Sohn P, Weaver SA, Robertson MA, Petrache I, et al: Cigarette smoke exposure impairs β-cell function through activation of oxidative stress and ceramide accumulation. Mol Metab. 37:1009752020. View Article : Google Scholar

97 

Xu YN, Wang Z, Zhang SK, Xu JR, Pan ZX, Wei X, Wen HH, Luo YS, Guo MJ and Zhu Q: Low-grade elevation of palmitate and lipopolysaccharide synergistically induced β-cell damage via inhibition of neutral ceramidase. Mol Cell Endocrinol. 539:1114732022. View Article : Google Scholar

98 

Šrámek J, Němcová-Fürstová V and Kovář J: Molecular mechanisms of apoptosis induction and its regulation by fatty acids in pancreatic β-cells. Int J Mol Sci. 22:42852021. View Article : Google Scholar

99 

Canals D, Salamone S and Hannun YA: Visualizing bioactive ceramides. Chem Phys Lipids. 216:142–151. 2018. View Article : Google Scholar : PubMed/NCBI

100 

Marra F and Svegliati-Baroni G: Lipotoxicity and the gut-liver axis in NASH pathogenesis. J Hepatol. 68:280–295. 2018. View Article : Google Scholar

101 

Meikle PJ and Summers SA: Sphingolipids and phospholipids in insulin resistance and related metabolic disorders. Nat Rev Endocrinol. 13:79–91. 2017. View Article : Google Scholar

102 

Bandet CL, Tan-Chen S, Bourron O, Stunff HL and Hajduch E: Sphingolipid metabolism: New insight into ceramide-induced lipotoxicity in muscle cells. Int J Mol Sci. 20:4792019. View Article : Google Scholar : PubMed/NCBI

103 

Fang Z, Pyne S and Pyne NJ: Ceramide and sphingosine 1-phosphate in adipose dysfunction. Prog Lipid Res. 74:145–159. 2019. View Article : Google Scholar : PubMed/NCBI

104 

Bekhite M, González-Delgado A, Hübner S, Haxhikadrija P, Kretzschmar T, Müller T, Wu JMF, Bekfani T, Franz M, Wartenberg M, et al: The role of ceramide accumulation in human induced pluripotent stem cell-derived cardiomyocytes on mitochondrial oxidative stress and mitophagy. Free Radic Biol Med. 167:66–80. 2021. View Article : Google Scholar : PubMed/NCBI

105 

Chavez JA, Knotts TA, Wang LP, Li G, Dobrowsky RT, Florant GL and Summers SA: A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem. 278:10297–10303. 2003. View Article : Google Scholar : PubMed/NCBI

106 

Zalewska A, Maciejczyk M, Szulimowska J, Imierska M and Błachnio-Zabielska A: High-fat diet affects ceramide content, disturbs mitochondrial redox balance, and induces apoptosis in the submandibular glands of mice. Biomolecules. 9:8772019. View Article : Google Scholar : PubMed/NCBI

107 

Holland WL, Brozinick JT, Wang LP, Hawkins ED, Sargent KM, Liu Y, Narra K, Hoehn KL, Knotts TA, Siesky A, et al: Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab. 5:167–179. 2007. View Article : Google Scholar : PubMed/NCBI

108 

Petersen MC and Shulman GI: Mechanisms of insulin action and insulin resistance. Physiol Rev. 98:2133–2223. 2018. View Article : Google Scholar : PubMed/NCBI

109 

Gasparini SJ, Swarbrick MM, Kim S, Thai LJ, Henneicke H, Cavanagh LL, Tu J, Weber MC, Zhou H and Seibel MJ: Androgens sensitise mice to glucocorticoid-induced insulin resistance and fat accumulation. Diabetologia. 62:1463–1477. 2019. View Article : Google Scholar : PubMed/NCBI

110 

Linn SC, Kim HS, Keane EM, Andras LM, Wang E and Merrill AH Jr: Regulation of de novo sphingolipid biosynthesis and the toxic consequences of its disruption. Biochem Soc Trans. 29:831–835. 2001. View Article : Google Scholar : PubMed/NCBI

111 

Choi KM, Lee YS, Choi MH, Sin DM, Lee S, Ji SY, Lee MK, Lee YM, Yun YP, Hong JT and Yoo HS: Inverse relationship between adipocyte differentiation and ceramide level in 3T3-L1 cells. Biol Pharm Bull. 34:912–916. 2011. View Article : Google Scholar : PubMed/NCBI

112 

Li Y, Talbot CL, Chandravanshi B, Ksiazek A, Sood A, Chowdhury KH, Maschek JA, Cox J, Babu AKS, Paz HA, et al: Cordyceps inhibits ceramide biosynthesis and improves insulin resistance and hepatic steatosis. Sci Rep. 12:72732022. View Article : Google Scholar : PubMed/NCBI

113 

Kumar DP, Caffrey R, Marioneaux J, Santhekadur PK, Bhat M, Alonso C, Koduru SV, Philip B, Jain MR, Giri SR, et al: The PPAR α/γ agonist saroglitazar improves insulin resistance and steatohepatitis in a diet induced animal model of nonalcoholic fatty liver disease. Sci Rep. 10:93302020. View Article : Google Scholar

114 

Kucuk S, Niven J, Caamano J, Jones SW, Camacho-Muñoz D, Nicolaou A and Mauro C: Unwrapping the mechanisms of ceramide and fatty acid-initiated signals leading to immune-inflammatory responses in obesity. Int J Biochem Cell Biol. 135:1059722021. View Article : Google Scholar : PubMed/NCBI

115 

Gilbert M: Role of skeletal muscle lipids in the pathogenesis of insulin resistance of obesity and type 2 diabetes. J Diabetes Investig. 12:1934–1941. 2021. View Article : Google Scholar : PubMed/NCBI

116 

Reidy PT, Mahmassani ZS, McKenzie AI, Petrocelli JJ, Summers SA and Drummond MJ: Influence of exercise training on skeletal muscle insulin resistance in aging: Spotlight on muscle ceramides. Int J Mol Sci. 21:15142020. View Article : Google Scholar : PubMed/NCBI

117 

Coen PM and Goodpaster BH: Role of intramyocelluar lipids in human health. Trends Endocrinol Metab. 23:391–398. 2012. View Article : Google Scholar : PubMed/NCBI

118 

Galadari S, Rahman A, Pallichankandy S, Galadari A and Thayyullathil F: Role of ceramide in diabetes mellitus: Evidence and mechanisms. Lipids Health Dis. 12:982013. View Article : Google Scholar : PubMed/NCBI

119 

Choi RH, Tatum SM, Symons JD, Summers SA and Holland WL: Ceramides and other sphingolipids as drivers of cardiovascular disease. Nat Rev Cardiol. 18:701–711. 2021. View Article : Google Scholar : PubMed/NCBI

120 

Edsfeldt A, Dunér P, Ståhlman M, Mollet IG, Asciutto G, Grufman AHM, Nitulescu M, Persson AF, Fisher RM, Melander O, et al: Proinflammatory role of sphingolipids and glycosphingolipids in the human atherosclerotic plaque. Arterioscler Thromb Vasc Biol. 36:1132–1140. 2016. View Article : Google Scholar : PubMed/NCBI

121 

Wang P, Zeng G, Yan Y, Zhang SY, Dong Y, Zhang Y, Zhang X, Liu H, Zhang Z, Jiang C and Pang Y: Disruption of adipocyte HIF-1 α improves atherosclerosis through the inhibition of ceramide generation. Acta Pharm Sin B. 12:1899–1912. 2022. View Article : Google Scholar : PubMed/NCBI

122 

Yang RX, Pan Q, Liu XL, Zhou D, Xin FZ, Zhao ZH, Zhang RN, Zeng J, Qiao L, Hu CX, et al: Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis. Lipids Health Dis. 18:1792019. View Article : Google Scholar : PubMed/NCBI

123 

Zhang X, Zhang Y, Wang P, Zhang SY, Dong Y, Zeng G, Yan Y, Sun L, Wu Q, Liu H, et al: Adipocyte hypoxia-inducible factor 2α suppresses atherosclerosis by promoting adipose ceramide catabolism. Cell Metab. 30:937–951.e5. 2019. View Article : Google Scholar

124 

Dany M, Gencer S, Nganga R, Thomas RJ, Oleinik N, Baron KD, Szulc ZM, Ruvolo P, Kornblau S, Andreeff M and Ogretmen B: Targeting FLT3-ITD signaling mediates ceramide-dependent mitophagy and attenuates drug resistance in AML. Blood. 128:1944–1958. 2016. View Article : Google Scholar : PubMed/NCBI

125 

Zhang Y, Huang NQ, Yan F, Jin H, Zhou SY, Shi JS and Jin F: Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link. Behav Brain Res. 339:57–65. 2018. View Article : Google Scholar

126 

Yang Y, Xu G, Xu Y, Cheng X, Xu S, Chen S and Wu L: Ceramide mediates radiation-induced germ cell apoptosis via regulating mitochondria function and MAPK factors in caenorhabditis elegans. Ecotoxicol Environ Saf. 208:1115792021. View Article : Google Scholar : PubMed/NCBI

127 

Ganesan V, Perera MN, Colombini D, Datskovskiy D, Chadha K and Colombini M: Ceramide and activated Bax act synergistically to permeabilize the mitochondrial outer membrane. Apoptosis. 15:553–562. 2010. View Article : Google Scholar : PubMed/NCBI

128 

James BN, Oyeniran C, Sturgill JL, Newton J, Martin RK, Bieberich E, Weigel C, Maczis MA, Palladino END, Lownik JC, et al: Ceramide in apoptosis and oxidative stress in allergic inflammation and asthma. J Allergy Clin Immunol. 147:1936–1948.e9. 2021. View Article : Google Scholar :

129 

Römer A, Linn T and Petry SF: Lipotoxic impairment of mitochondrial function in β-cells: A review. Antioxidants (Basel). 10:2932021. View Article : Google Scholar

130 

Onyango AN: Cellular stresses and stress responses in the pathogenesis of insulin resistance. Oxid Med Cell Longev. 2018:43217142018. View Article : Google Scholar : PubMed/NCBI

131 

Ueda N: A rheostat of ceramide and sphingosine-1-phosphate as a determinant of oxidative stress-mediated kidney injury. Int J Mol Sci. 23:40102022. View Article : Google Scholar : PubMed/NCBI

132 

Poole LP and Macleod KF: Mitophagy in tumorigenesis and metastasis. Cell Mol Life Sci. 78:3817–3851. 2021. View Article : Google Scholar : PubMed/NCBI

133 

Srivastava S and Chan C: Hydrogen peroxide and hydroxyl radicals mediate palmitate-induced cytotoxicity to hepatoma cells: Relation to mitochondrial permeability transition. Free Radic Res. 41:38–49. 2007. View Article : Google Scholar

134 

Law BA, Liao X, Moore KS, Southard A, Roddy P, Ji R, Szulc Z, Bielawska A, Schulze PC and Cowart LA: Lipotoxic very-long-chain ceramides cause mitochondrial dysfunction, oxidative stress, and cell death in cardiomyocytes. FASEB J. 32:1403–1416. 2018. View Article : Google Scholar :

135 

Botta A, Elizbaryan K, Tashakorinia P, Lam NH and Sweeney G: An adiponectin-S1P autocrine axis protects skeletal muscle cells from palmitate-induced cell death. Lipids Health Dis. 19:1562020. View Article : Google Scholar : PubMed/NCBI

136 

Simon JN, Chowdhury SAK, Warren CM, Sadayappan S, Wieczorek DF, Solaro RJ and Wolska BM: Ceramide-mediated depression in cardiomyocyte contractility through PKC activation and modulation of myofilament protein phosphorylation. Basic Res Cardiol. 109:4452014. View Article : Google Scholar : PubMed/NCBI

137 

Kim C and Kim B: Anti-cancer natural products and their bioactive compounds inducing ER stress-mediated apoptosis: A review. Nutrients. 10:10212018. View Article : Google Scholar : PubMed/NCBI

138 

Hu H, Tian M, Ding C and Yu S: The C/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection. Front Immunol. 9:30832019. View Article : Google Scholar : PubMed/NCBI

139 

Xiang C, Wang Y, Zhang H and Han F: The role of endoplasmic reticulum stress in neurodegenerative disease. Apoptosis. 22:1–26. 2017. View Article : Google Scholar

140 

Szpigel A, Hainault I, Carlier A, Venteclef N, Batto AF, Hajduch E, Bernard C, Ktorza A, Gautier JF, Ferré P, et al: Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes. Diabetologia. 61:399–412. 2018. View Article : Google Scholar

141 

Xu G, Chen J, Jing G, Grayson TB and Shalev A: miR-204 targets PERK and regulates UPR signaling and β-cell apoptosis. Mol Endocrinol. 30:917–924. 2016. View Article : Google Scholar : PubMed/NCBI

142 

Ojo OA, Grant S, Amanze JC, Oni AI, Ojo AB, Elebiyo TC, Obafemi TO, Ayokunle DI and Ogunlakin AD: Annona muricata L. peel extract inhibits carbohydrate metabolizing enzymes and reduces pancreatic β-cells, inflammation, and apoptosis via upregulation of PI3K/AKT genes. PLoS One. 17:e02769842022. View Article : Google Scholar

143 

Wang Y, Liu J, Akatsu C, Zhang R, Zhang H, Zhu H, Liu K, Zhu HY, Min Q, Meng X, et al: LAPTM5 mediates immature B cell apoptosis and B cell tolerance by regulating the WWP2-PTEN-AKT pathway. Proc Natl Acad Sci USA. 119:e22056291192022. View Article : Google Scholar : PubMed/NCBI

144 

Hsu CM, Lin JJ, Su JH and Liu CI: 13-Acetoxysarcocrassolide induces apoptosis in human hepatocellular carcinoma cells through mitochondrial dysfunction and suppression of the PI3K/AKT/mTOR/p70S6K signalling pathway. Pharm Biol. 60:2276–2285. 2022. View Article : Google Scholar : PubMed/NCBI

145 

Cui F and He X: IGF-1 ameliorates streptozotocin-induced pancreatic β cell dysfunction and apoptosis via activating IRS1/PI3K/Akt/FOXO1 pathway. Inflamm Res. 71:669–680. 2022. View Article : Google Scholar : PubMed/NCBI

146 

Denhez B, Rousseau M, Spino C, Dancosst DA, Dumas MÈ, Guay A, Lizotte F and Geraldes P: Saturated fatty acids induce insulin resistance in podocytes through inhibition of IRS1 via activation of both IKKβ and mTORC1. Sci Rep. 10:216282020. View Article : Google Scholar

147 

Jennemann R, Kaden S, Volz M, Nordström V, Herzer S, Sandhoff R and Gröne HJ: Gangliosides modulate insulin secretion by pancreatic beta cells under glucose stress. Glycobiology. 30:722–734. 2020. View Article : Google Scholar : PubMed/NCBI

148 

Benito-Vicente A, Jebari-Benslaiman S, Galicia-Garcia U, Larrea-Sebal A, Uribe KB and Martin C: Molecular mechanisms of lipotoxicity-induced pancreatic β-cell dysfunction. Int Rev Cell Mol Biol. 359:357–402. 2021. View Article : Google Scholar

149 

Huang X, Liu G, Guo J and Su Z: The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci. 14:1483–1496. 2018. View Article : Google Scholar : PubMed/NCBI

150 

Obanda DN, Ribnicky D, Yu Y, Stephens J and Cefalu WT: An extract of Urtica dioica L. mitigates obesity induced insulin resistance in mice skeletal muscle via protein phosphatase 2A (PP2A). Sci Rep. 6:222222016. View Article : Google Scholar : PubMed/NCBI

151 

Li J, Huang J, Lu J, Guo Z, Li Z, Gao H, Wang P, Luo W, Cai S, Hu Y, et al: Sirtuin 1 represses PKC-ζ activity through regulating interplay of acetylation and phosphorylation in cardiac hypertrophy. Br J Pharmacol. 176:416–435. 2019.

152 

Ivey RA, Sajan MP and Farese RV: Requirements for pseudosubstrate arginine residues during autoinhibition and phosphatidylinositol 3,4,5-(PO4)3-dependent activation of atypical PKC. J Biol Chem. 289:25021–25030. 2014. View Article : Google Scholar : PubMed/NCBI

153 

Campana M, Bellini L, Rouch C, Rachdi L, Coant N, Butin N, Bandet CL, Philippe E, Meneyrol K, Kassis N, et al: Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats. Mol Metab. 8:23–36. 2018. View Article : Google Scholar

154 

Wali JA, Jarzebska N, Raubenheimer D, Simpson SJ, Rodionov RN and O'Sullivan JF: Cardio-metabolic effects of high-fat diets and their underlying mechanisms-a narrative review. Nutrients. 12:15052020. View Article : Google Scholar : PubMed/NCBI

155 

Huang H, Aminian A, Hassan M, Dan O, Axelrod CL, Schauer PR, Brethauer SA and Kirwan JP: Gastric bypass surgery improves the skeletal muscle ceramide/S1P ratio and upregulates the AMPK/SIRT1/PGC-1α pathway in Zucker diabetic fatty rats. Obes Surg. 29:2158–2165. 2019. View Article : Google Scholar : PubMed/NCBI

156 

Matsuzaka T, Kuba M, Koyasu S, Yamamoto Y, Motomura K, Arulmozhiraja S, Ohno H, Sharma R, Shimura T, Okajima Y, et al: Hepatocyte ELOVL fatty acid elongase 6 determines ceramide Acyl-chain length and hepatic insulin sensitivity in mice. Hepatology. 71:1609–1625. 2020. View Article : Google Scholar

157 

Yazıcı D and Sezer H: Insulin resistance, obesity and lipotoxicity. Engin AB and Engin A: Obesity and Lipotoxicity. Advances in Experimental Medicine and Biology. 960. Springer International Publishing; pp. 277–304. 2017, View Article : Google Scholar

158 

Xia QS, Lu FE, Wu F, Huang ZY, Dong H, Xu LJ and Gong J: New role for ceramide in hypoxia and insulin resistance. World J Gastroenterol. 26:2177–2186. 2020. View Article : Google Scholar : PubMed/NCBI

159 

Obata Y, Kita S, Koyama Y, Fukuda S, Takeda H, Takahashi M, Fujishima Y, Nagao H, Masuda S, Tanaka Y, et al: Adiponectin/T-cadherin system enhances exosome biogenesis and decreases cellular ceramides by exosomal release. JCI Insight. 3:e996802018. View Article : Google Scholar : PubMed/NCBI

160 

Santovito D, De Nardis V, Marcantonio P, Mandolini C, Paganelli C, Vitale E, Buttitta F, Bucci M, Mezzetti A, Consoli A and Cipollone F: Plasma exosome microRNA profiling unravels a new potential modulator of adiponectin pathway in diabetes: Effect of glycemic control. J Clin Endocrinol Metab. 99:E1681–E1685. 2014. View Article : Google Scholar : PubMed/NCBI

161 

Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, Ofrecio JM, Wollam J, Hernandez-Carretero A, Fu W, et al: Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell. 171:372–384.e12. 2017. View Article : Google Scholar

162 

Tian F, Tang P, Sun Z, Zhang R, Zhu D, He J, Liao J, Wan Q and Shen J: miR-210 in exosomes derived from macrophages under high glucose promotes mouse diabetic obesity pathogenesis by suppressing NDUFA4 expression. J Diabetes Res. 2020:68946842020. View Article : Google Scholar : PubMed/NCBI

163 

Ruiz-León AM, Lapuente M, Estruch R and Casas R: Clinical advances in immunonutrition and atherosclerosis: A review. Front Immunol. 10:8372019. View Article : Google Scholar : PubMed/NCBI

164 

Geovanini GR and Libby P: Atherosclerosis and inflammation: Overview and updates. Clin Sci (Lond). 132:1243–1252. 2018. View Article : Google Scholar : PubMed/NCBI

165 

Ho QWC, Zheng X and Ali Y: Ceramide Acyl chain length and its relevance to intracellular lipid regulation. Int J Mol Sci. 23:96972022. View Article : Google Scholar : PubMed/NCBI

166 

Sindhu S, Leung YH, Arefanian H, Madiraju SRM, Al-Mulla F, Ahmad R and Prentki M: Neutral sphingomyelinase-2 and cardiometabolic diseases. Obes Rev. 22:e132482021. View Article : Google Scholar : PubMed/NCBI

167 

Chen X, Guo X, Ge Q, Zhao Y, Mu H and Zhang J: ER stress activates the NLRP3 inflammasome: A novel mechanism of atherosclerosis. Oxid Med Cell Longev. 2019:34625302019. View Article : Google Scholar : PubMed/NCBI

168 

Alaaeldin R, Abdel-Rahman IAM, Hassan HA, Youssef N, Allam AE, Abdelwahab SF, Zhao QL and Fathy M: Carpachromene ameliorates insulin resistance in HepG2 cells via modulating IR/IRS1/PI3k/Akt/GSK3/FoxO1 pathway. Molecules. 26:76292021. View Article : Google Scholar : PubMed/NCBI

169 

Gündüz D, Troidl C, Tanislav C, Rohrbach S, Hamm C and Aslam M: Role of PI3K/Akt and MEK/ERK signalling in cAMP/Epac-mediated endothelial barrier stabilisation. Front Physiol. 10:13872019. View Article : Google Scholar : PubMed/NCBI

170 

Prasad M, Gatasheh MK, Alshuniaber MA, Krishnamoorthy R, Rajagopal P, K rishnamoor thy K, Periyasamy V, Veeraraghavan VP and Jayaraman S: Impact of glyphosate on the development of insulin resistance in experimental diabetic rats: Role of NFκB signalling pathways. Antioxidants (Basel). 11:24362022. View Article : Google Scholar

171 

Wright CJ, McKenna S, De Dios R, Boehmer BH, Nguyen L, Ghosh S, Sandoval J and Rozance PJ: Lower threshold to NFκB activity sensitizes murine β-cells to streptozotocin. J Endocrinol. 249:163–175. 2021. View Article : Google Scholar : PubMed/NCBI

172 

Lin Z, Ge J, Wang Z, Ren J, Wang X, Xiong H, Gao J, Zhang Y and Zhang Q: Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk. Sci Rep. 7:424982017. View Article : Google Scholar : PubMed/NCBI

173 

Olona A, Hateley C, Muralidharan S, Wenk MR, Torta F and Behmoaras J: Sphingolipid metabolism during Toll-like receptor 4 (TLR4)-mediated macrophage activation. Br J Pharmacol. 178:4575–4587. 2021. View Article : Google Scholar : PubMed/NCBI

174 

Engin A: The pathogenesis of obesity-associated adipose tissue inflammation. Obesity and Lipotoxicity. Advances in Experimental Medicine and Biology. Engin AB and Engin A: 960. Springer International Publishing; pp. 221–245. 2017, View Article : Google Scholar

175 

Berg M, Polyzos KA, Agardh H, Baumgartner R, Forteza MJ, Kareinen I, Gisterå A, Bottcher G, Hurt-Camejo E, Hansson GK and Ketelhuth DFJ: 3-Hydroxyanthralinic acid metabolism controls the hepatic SREBP/lipoprotein axis, inhibits inflammasome activation in macrophages, and decreases atherosclerosis in Ldlr-/- mice. Cardiovasc Res. 116:1948–1957. 2020. View Article : Google Scholar

176 

Hornemann T and Worgall TS: Sphingolipids and atherosclerosis. Atherosclerosis. 226:16–28. 2013. View Article : Google Scholar

177 

Dekker MJ, Baker C, Naples M, Samsoondar J, Zhang R, Qiu W, Sacco J and Adeli K: Inhibition of sphingolipid synthesis improves dyslipidemia in the diet-induced hamster model of insulin resistance: Evidence for the role of sphingosine and sphinganine in hepatic VLDL-apoB100 overproduction. Atherosclerosis. 228:98–109. 2013. View Article : Google Scholar : PubMed/NCBI

178 

Yang J and Liu Z: Mechanistic pathogenesis of endothelial dysfunction in diabetic nephropathy and retinopathy. Front Endocrinol (Lausanne). 13:8164002022. View Article : Google Scholar : PubMed/NCBI

179 

Sharma S, Schaper N and Rayman G: Microangiopathy: Is it relevant to wound healing in diabetic foot disease? Diabetes Metab Res Rev. 36(Suppl 1): e32442020. View Article : Google Scholar

180 

Wang S, Lei B, Zhang E, Gong P, Gu J, He L, Han L and Yuan Z: Targeted therapy for inflammatory diseases with mesenchymal stem cells and their derived exosomes: From basic to clinics. Int J Nanomedicine. 17:1757–1781. 2022. View Article : Google Scholar : PubMed/NCBI

181 

Gil CL, Hooker E and Larrivée B: Diabetic kidney disease, endothelial damage, and podocyte-endothelial crosstalk. Kidney Med. 3:105–115. 2020. View Article : Google Scholar

182 

Zhao WN, Xu SQ, Liang JF, Peng L, Liu HL, Wang Z, Fang Q, Wang M, Yin WQ, Zhang WJ and Lou JN: Endothelial progenitor cells from human fetal aorta cure diabetic foot in a rat model. Metabolism. 65:1755–1767. 2016. View Article : Google Scholar : PubMed/NCBI

183 

Basra R, Papanas N, Farrow F, Karalliedde J and Vas P: Diabetic foot ulcers and cardiac autonomic neuropathy. Clin Ther. 44:323–330. 2022. View Article : Google Scholar : PubMed/NCBI

184 

King RJ, Harrison L, Gilbey SG, Santhakumar A, Wyatt J, Jones R and Bodansky HJ: Diabetic hepatosclerosis: Another diabetes microvascular complication? Diabet Med. 33:e5–e7. 2016. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Sun Z, Zang G, Zhang L and Wang Z: Role of ceramides in diabetic foot ulcers (Review). Int J Mol Med 51: 26, 2023.
APA
Wang, Y., Sun, Z., Zang, G., Zhang, L., & Wang, Z. (2023). Role of ceramides in diabetic foot ulcers (Review). International Journal of Molecular Medicine, 51, 26. https://doi.org/10.3892/ijmm.2023.5229
MLA
Wang, Y., Sun, Z., Zang, G., Zhang, L., Wang, Z."Role of ceramides in diabetic foot ulcers (Review)". International Journal of Molecular Medicine 51.3 (2023): 26.
Chicago
Wang, Y., Sun, Z., Zang, G., Zhang, L., Wang, Z."Role of ceramides in diabetic foot ulcers (Review)". International Journal of Molecular Medicine 51, no. 3 (2023): 26. https://doi.org/10.3892/ijmm.2023.5229
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Sun Z, Zang G, Zhang L and Wang Z: Role of ceramides in diabetic foot ulcers (Review). Int J Mol Med 51: 26, 2023.
APA
Wang, Y., Sun, Z., Zang, G., Zhang, L., & Wang, Z. (2023). Role of ceramides in diabetic foot ulcers (Review). International Journal of Molecular Medicine, 51, 26. https://doi.org/10.3892/ijmm.2023.5229
MLA
Wang, Y., Sun, Z., Zang, G., Zhang, L., Wang, Z."Role of ceramides in diabetic foot ulcers (Review)". International Journal of Molecular Medicine 51.3 (2023): 26.
Chicago
Wang, Y., Sun, Z., Zang, G., Zhang, L., Wang, Z."Role of ceramides in diabetic foot ulcers (Review)". International Journal of Molecular Medicine 51, no. 3 (2023): 26. https://doi.org/10.3892/ijmm.2023.5229
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