Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Potential Role of SUMO and SUMOylation in the Pathogenesis of Diabetes Mellitus

Author(s): Mahvash Sadeghi, Sajad Dehnavi, Mojtaba Shohan, Tannaz Jamialahmadi, Thozhukat Sathyapalan and Amirhossein Sahebkar*

Volume 30, Issue 14, 2023

Published on: 23 September, 2022

Page: [1623 - 1637] Pages: 15

DOI: 10.2174/0929867329666220817142848

Price: $65


Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia and associated with multiple organ systems complications. The incidence and prevalence of diabetes are increasing in an epidemic proportion worldwide. In addition to environmental factors, some epigenetic and post-translational modifications have critical roles in the pathogenesis of diabetes and its complications. Reversible covalent modification such as SUMOylation by SUMO (Small Ubiquitin-like Modifier) has emerged as a new mechanism that affects the dynamic regulation of proteins. In this review, we initially focus on the function of SUMO and SUMOylation. Subsequently, we assess the potential effects of this process in the pathogenesis of type 1 and 2 diabetes mellitus.

Keywords: Diabetes mellitus, Small Ubiquitin-like modifier, SUMO, SUMOylation, hyperglycemia, epigenetic.

Mathis, D.; Vence, L.; Benoist, C. β-Cell death during progression to diabetes. Nature, 2001, 414(6865), 792-798.
[] [PMID: 11742411]
Al-Haddad, R.; Karnib, N.; Assaad, R.A.; Bilen, Y.; Emmanuel, N.; Ghanem, A.; Younes, J.; Zibara, V.; Stephan, J.S.; Sleiman, S.F. Epigenetic changes in diabetes. Neurosci. Lett., 2016, 625, 64-69.
[] [PMID: 27130819]
Shaw, J.E.; Sicree, R.A.; Zimmet, P.Z. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res. Clin. Pract., 2010, 87(1), 4-14.
[] [PMID: 19896746]
Noso, S.; Fujisawa, T.; Kawabata, Y.; Asano, K.; Hiromine, Y.; Fukai, A.; Ogihara, T.; Ikegami, H. Association of small ubiquitin-like modifier 4 (SUMO4) variant, located in IDDM5 locus, with type 2 diabetes in the Japanese population. J. Clin. Endocrinol. Metab., 2007, 92(6), 2358-2362.
[] [PMID: 17374705]
American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care, 2013, 36(4), 1033-1046.
[] [PMID: 23468086]
Scheen, A. Diabetes mellitus in the elderly: Insulin resistance and/or impaired insulin secretion? Diabetes Metabol., 2005, 31, 5S27-5S34.
Mercado, M.M.; McLenithan, J.C.; Silver, K.D.; Shuldiner, A.R. Genetics of insulin resistance. Curr. Diab. Rep., 2002, 2(1), 83-95.
[] [PMID: 12643127]
Todd, J.A. Etiology of type 1 diabetes. Immunity, 2010, 32(4), 457-467.
[] [PMID: 20412756]
Feil, R.; Fraga, M.F. Epigenetics and the environment: Emerging patterns and implications. Nat. Rev. Genet., 2012, 13(2), 97-109.
[] [PMID: 22215131]
Bird, A. Perceptions of epigenetics. Nature, 2007, 447(7143), 396-398.
[] [PMID: 17522671]
Dohmen, R.J. SUMO protein modification. Biochim. Biophys. Acta, 2004, 1695(1-3), 113-131.
Shetty, P.M.V.; Rangrez, A.Y.; Frey, N. SUMO proteins in the cardiovascular system: Friend or foe? J. Biomed. Sci., 2020, 27(1), 98.
[] [PMID: 33099299]
Su, S.; Zhang, Y.; Liu, P. Roles of ubiquitination and SUMOylation in DNA damage response. Curr. Issues Mol. Biol., 2020, 35(1), 59-84.
[] [PMID: 31422933]
Flotho, A.; Melchior, F. Sumoylation: A regulatory protein modification in health and disease. Annu. Rev. Biochem., 2013, 82(1), 357-385.
[] [PMID: 23746258]
Baczyk, D.; Audette, M.C.; Drewlo, S.; Levytska, K.; Kingdom, J.C. SUMO-4: A novel functional candidate in the human placental protein SUMOylation machinery. PLoS One, 2017, 12(5), e0178056.
[] [PMID: 28545138]
Liang, Y-C.; Lee, C-C.; Yao, Y-L.; Lai, C-C.; Schmitz, M.L.; Yang, W-M. SUMO5, a novel poly-SUMO isoform, regulates PML nuclear bodies. Sci. Rep., 2016, 6(1), 26509.
[] [PMID: 27211601]
Dehnavi, S., Sadeghi, M., Penson, P.E., Banach, M., Jamialahmadi, T., Sahebkar, A. The role of protein SUMOylation in the pathogenesis of atherosclerosis. J. Clin. Med., 20198(11), art. no. 1856.
Dehnavi, S.; Sadeghi, M.; Johnston, T.P.; Barreto, G.; Shohan, M.; Sahebkar, A. The role of protein SUMOylation in rheumatoid arthritis. J. Autoimmun., 2019, 102, 1-7.
[] [PMID: 31078376]
Yang, Y.; He, Y.; Wang, X.; Liang, Z.; He, G.; Zhang, P.; Zhu, H.; Xu, N.; Liang, S. Protein SUMOylation modification and its associations with disease. Open Biol., 2017, 7(10), 170167.
[] [PMID: 29021212]
Seeler, J-S.; Dejean, A. SUMO and the robustness of cancer. Nat. Rev. Cancer, 2017, 17(3), 184-197.
[] [PMID: 28134258]
Zhang, Q.; Liu, D.; Zhao, Z.Y.; Sun, Q.; Ding, L.X.; Wang, Y.X. Association between the SUMO4 M55V polymorphism and susceptibility to type 2 diabetes mellitus: A meta-analysis. Biomed. Environ. Sci., 2017, 30(4), 288-295.
[] [PMID: 28494838]
Li, H.; Lindholm, E.; Almgren, P.; Gustafsson, A.; Forsblom, C.; Groop, L.; Tuomi, T. Possible human leukocyte antigen-mediated genetic interaction between type 1 and type 2 Diabetes. J. Clin. Endocrinol. Metab., 2001, 86(2), 574-582.
[] [PMID: 11158011]
Kroetz, M.B. SUMO: A ubiquitin-like protein modifier. Yale J. Biol. Med., 2005, 78(4), 197-201.
[PMID: 16720014]
Shao, C.; Cobb, M.H. Sumoylation regulates the transcriptional activity of MafA in pancreatic β cells. J. Biol. Chem., 2009, 284(5), 3117-3124.
[] [PMID: 19029092]
Dai, X-Q.; Kolic, J.; Marchi, P.; Sipione, S.; Macdonald, P.E. SUMOylation regulates Kv2.1 and modulates pancreatic β-cell excitability. J. Cell Sci., 2009, 122(Pt 6), 775-779.
[] [PMID: 19223394]
He, X.; Lai, Q.; Chen, C.; Li, N.; Sun, F.; Huang, W.; Zhang, S.; Yu, Q.; Yang, P.; Xiong, F.; Chen, Z.; Gong, Q.; Ren, B.; Weng, J.; Eizirik, D.L.; Zhou, Z.; Wang, C.Y. Both conditional ablation and overexpression of E2 SUMO-conjugating enzyme (UBC9) in mouse pancreatic beta cells result in impaired beta cell function. Diabetologia, 2018, 61(4), 881-895.
[] [PMID: 29299635]
Dai, X-Q.; Plummer, G.; Casimir, M.; Kang, Y.; Hajmrle, C.; Gaisano, H.Y.; Manning Fox, J.E.; MacDonald, P.E. SUMOylation regulates insulin exocytosis downstream of secretory granule docking in rodents and humans. Diabetes, 2011, 60(3), 838-847.
[] [PMID: 21266332]
Xu, G.; Kaneto, H.; Laybutt, D.R.; Duvivier-Kali, V.F.; Trivedi, N.; Suzuma, K.; King, G.L.; Weir, G.C.; Bonner-Weir, S. Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: Possible contribution to impaired incretin effects in diabetes. Diabetes, 2007, 56(6), 1551-1558.
[] [PMID: 17360984]
Rajan, S.; Torres, J.; Thompson, M.S.; Philipson, L.H. SUMO downregulates GLP-1-stimulated cAMP generation and insulin secretion. Am. J. Physiol. Endocrinol. Metab., 2012, 302(6), E714-E723.
[] [PMID: 22234371]
Hansen, K.B.; Vilsbøll, T.; Bagger, J.I.; Holst, J.J.; Knop, F.K. Reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet impairs the incretin effect in healthy subjects. J. Clin. Endocrinol. Metab., 2010, 95(7), 3309-3317.
[] [PMID: 20410219]
Knop, F.K.; Vilsbøll, T.; Højberg, P.V.; Larsen, S.; Madsbad, S.; Vølund, A.; Holst, J.J.; Krarup, T. Reduced incretin effect in type 2 diabetes: Cause or consequence of the diabetic state? Diabetes, 2007, 56(8), 1951-1959.
[] [PMID: 17513701]
Nauck, M.A.; Meier, J.J. Individualised incretin-based treatment for type 2 diabetes. Lancet, 2010, 376(9739), 393-394.
[] [PMID: 20580425]
Geiss-Friedlander, R.; Melchior, F. Concepts in sumoylation: A decade on. Nat. Rev. Mol. Cell Biol., 2007, 8(12), 947-956.
[] [PMID: 18000527]
Palacios, S.; Perez, L.H.; Welsch, S.; Schleich, S.; Chmielarska, K.; Melchior, F.; Locker, J.K. Quantitative SUMO-1 modification of a vaccinia virus protein is required for its specific localization and prevents its self-association. Mol. Biol. Cell, 2005, 16(6), 2822-2835.
[] [PMID: 15800065]
Davey, J.S.; Carmichael, R.E.; Craig, T.J. Protein SUMOylation regulates insulin secretion at multiple stages. Sci. Rep., 2019, 9(1), 2895.
[] [PMID: 30814610]
Fajans, S.S.; Bell, G.I.; Polonsky, K.S. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N. Engl. J. Med., 2001, 345(13), 971-980.
[] [PMID: 11575290]
Mitchell, S.M.; Frayling, T.M. The role of transcription factors in maturity-onset diabetes of the young. Mol. Genet. Metab., 2002, 77(1-2), 35-43.
[] [PMID: 12359128]
Estrada, K.; Aukrust, I.; Bjørkhaug, L.; Burtt, N.P.; Mercader, J.M.; García-Ortiz, H.; Huerta-Chagoya, A.; Moreno-Macías, H.; Walford, G.; Flannick, J.; Williams, A.L.; Gómez-Vázquez, M.J.; Fernandez-Lopez, J.C.; Martínez-Hernández, A.; Jiménez-Morales, S.; Centeno-Cruz, F.; Mendoza-Caamal, E.; Revilla-Monsalve, C.; Islas-Andrade, S.; Córdova, E.J.; Soberón, X.; González-Villalpando, M.E.; Henderson, E.; Wilkens, L.R.; Le Marchand, L.; Arellano-Campos, O.; Ordóñez-Sánchez, M.L.; Rodríguez-Torres, M.; Rodríguez-Guillén, R.; Riba, L.; Najmi, L.A.; Jacobs, S.B.; Fennell, T.; Gabriel, S.; Fontanillas, P.; Hanis, C.L.; Lehman, D.M.; Jenkinson, C.P.; Abboud, H.E.; Bell, G.I.; Cortes, M.L.; Boehnke, M.; González-Villalpando, C.; Orozco, L.; Haiman, C.A.; Tusié-Luna, T.; Aguilar-Salinas, C.A.; Altshuler, D.; Njølstad, P.R.; Florez, J.C.; MacArthur, D.G. Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population. JAMA, 2014, 311(22), 2305-2314.
[] [PMID: 24915262]
Morita, K.; Saruwatari, J.; Tanaka, T.; Oniki, K.; Kajiwara, A.; Otake, K.; Ogata, Y.; Nakagawa, K. Associations between the common HNF1A gene variant p.I27L (rs1169288) and risk of type 2 diabetes mellitus are influenced by weight. Diabetes Metab., 2015, 41(1), 91-94.
[] [PMID: 24933231]
Najmi, L.A.; Aukrust, I.; Flannick, J.; Molnes, J.; Burtt, N.; Molven, A.; Groop, L.; Altshuler, D.; Johansson, S.; Bjørkhaug, L.; Njølstad, P.R. Functional investigations of HNF1A identify rare variants as risk factors for type 2 diabetes in the general population. Diabetes, 2017, 66(2), 335-346.
[] [PMID: 27899486]
Kaci, A.; Keindl, M.; Solheim, M.H.; Njølstad, P.R.; Bjørkhaug, L.; Aukrust, I. The E3 SUMO ligase PIASγ is a novel interaction partner regulating the activity of diabetes associated hepatocyte nuclear factor-1α. Sci. Rep., 2018, 8(1), 1-14.
[] [PMID: 29311619]
Rajpal, G.; Schuiki, I.; Liu, M.; Volchuk, A.; Arvan, P. Action of protein disulfide isomerase on proinsulin exit from endoplasmic reticulum of pancreatic β-cells. J. Biol. Chem., 2012, 287(1), 43-47.
[] [PMID: 22105075]
Cunningham, C.N.; He, K.; Arunagiri, A.; Paton, A.W.; Paton, J.C.; Arvan, P.; Tsai, B. Chaperone-driven degradation of a misfolded proinsulin mutant in parallel with restoration of wild-type insulin secretion. Diabetes, 2017, 66(3), 741-753.
[] [PMID: 28028074]
Tersey, S.A.; Nishiki, Y.; Templin, A.T.; Cabrera, S.M.; Stull, N.D.; Colvin, S.C.; Evans-Molina, C.; Rickus, J.L.; Maier, B.; Mirmira, R.G. Islet β-cell endoplasmic reticulum stress precedes the onset of type 1 diabetes in the nonobese diabetic mouse model. Diabetes, 2012, 61(4), 818-827.
[] [PMID: 22442300]
Turano, C.; Coppari, S.; Altieri, F.; Ferraro, A. Proteins of the PDI family: Unpredicted non-ER locations and functions. J. Cell. Physiol., 2002, 193(2), 154-163.
[] [PMID: 12384992]
Li, N.; Luo, X.; Yu, Q.; Yang, P.; Chen, Z.; Wang, X.; Jiang, J.; Xu, J.; Gong, Q.; Eizirik, D.L.; Zhou, Z.; Zhao, J.; Xiong, F.; Zhang, S.; Wang, C.Y. SUMOylation of Pdia3 exacerbates proinsulin misfolding and ER stress in pancreatic beta cells. J. Mol. Med. (Berl.), 2020, 98(12), 1795-1807.
[] [PMID: 33159537]
Onishi, S.; Kataoka, K. PIASy is a SUMOylation-independent negative regulator of the insulin transactivator MafA. J. Mol. Endocrinol., 2019, 63(4), 297-308.
[] [PMID: 31614335]
Dadke, S.; Cotteret, S.; Yip, S-C.; Jaffer, Z.M.; Haj, F.; Ivanov, A.; Rauscher, F., III; Shuai, K.; Ng, T.; Neel, B.G.; Chernoff, J. Regulation of protein tyrosine phosphatase 1B by sumoylation. Nat. Cell Biol., 2007, 9(1), 80-85.
[] [PMID: 17159996]
Fioretto, P.; Bruseghin, M.; Berto, I.; Gallina, P.; Manzato, E.; Mussap, M. Renal protection in diabetes: Role of glycemic control. J. Am. Soc. Nephrol., 2006, 17(4)(Suppl. 2), S86-S89.
[] [PMID: 16565255]
Fukuda, H.; Sano, N.; Muto, S.; Horikoshi, M. Simple histone acetylation plays a complex role in the regulation of gene expression. Brief. Funct. Genomics Proteomics, 2006, 5(3), 190-208.
[] [PMID: 16980317]
Deepa, B.; Venkatraman Anuradha, C. Effects of linalool on inflammation, matrix accumulation and podocyte loss in kidney of streptozotocin-induced diabetic rats. Toxicol. Mech. Methods, 2013, 23(4), 223-234.
[] [PMID: 23193997]
Yaribeygi, H.; Atkin, S.L.; Sahebkar, A. Interleukin-18 and diabetic nephropathy: A review. J. Cell. Physiol., 2019, 234(5), 5674-5682.
[] [PMID: 30417374]
Dihazi, H.; Müller, G.A.; Lindner, S.; Meyer, M.; Asif, A.R.; Oellerich, M.; Strutz, F. Characterization of diabetic nephropathy by urinary proteomic analysis: Identification of a processed ubiquitin form as a differentially excreted protein in diabetic nephropathy patients. Clin. Chem., 2007, 53(9), 1636-1645.
[] [PMID: 17634209]
Siednienko, J.; Gorczyca, W.A. Regulation of NF-kappa B activity. Postepy Hig. Med. Dosw., 2003, 57(1), 19-32.
[PMID: 12765121]
Gao, C.; Huang, W.; Kanasaki, K.; Xu, Y. The role of ubiquitination and sumoylation in diabetic nephropathy. BioMed Res. Int., 2014, 2014, 160692.
[] [PMID: 24991536]
Ziyadeh, F.N. Mediators of diabetic renal disease: The case for tgf-Beta as the major mediator. J. Am. Soc. Nephrol., 2004, 15(90010)(Suppl. 1), S55-S57.
[] [PMID: 14684674]
Derynck, R.; Zhang, Y.E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature, 2003, 425(6958), 577-584.
[] [PMID: 14534577]
Imoto, S.; Ohbayashi, N.; Ikeda, O.; Kamitani, S.; Muromoto, R.; Sekine, Y.; Matsuda, T. Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-beta signaling. Biochem. Biophys. Res. Commun., 2008, 370(2), 359-365.
[] [PMID: 18384750]
Zhou, X; Gao, C; Huang, W; Yang, M; Chen, G; Jiang, L High glucose induces sumoylation of Smad4 via SUMO2/3 in mesangial cells. BioMed. Res. Int., 2014, 2014, 782625.
Manrique, C.; Lastra, G.; Sowers, J.R. New insights into insulin action and resistance in the vasculature. Ann. N. Y. Acad. Sci., 2014, 1311(1), 138-150.
[] [PMID: 24650277]
Derosa, G.; Sahebkar, A.; Maffioli, P. The role of various peroxisome proliferator-activated receptors and their ligands in clinical practice. J. Cell. Physiol., 2018, 233(1), 153-161.
[] [PMID: 28098353]
Devchand, P.R.; Liu, T.; Altman, R.B.; FitzGerald, G.A.; Schadt, E.E. The pioglitazone trek via human PPAR gamma: From discovery to a medicine at the FDA and beyond. Front. Pharmacol., 2018, 9, 1093.
[] [PMID: 30337873]
Zhang, Y.; Zhan, R-X.; Chen, J-Q.; Gao, Y.; Chen, L.; Kong, Y.; Zhong, X.J.; Liu, M.Q.; Chu, J.J.; Yan, G.Q.; Li, T.; He, M.; Huang, Q.R. Pharmacological activation of PPAR gamma ameliorates vascular endothelial insulin resistance via a non-canonical PPAR gamma-dependent nuclear factor-kappa B trans-repression pathway. Eur. J. Pharmacol., 2015, 754, 41-51.
[] [PMID: 25687252]
Armoni, M.; Harel, C.; Karnieli, E. PPARγ gene expression is autoregulated in primary adipocytes: Ligand, sumoylation, and isoform specificity. Horm. Metab. Res., 2015, 47(2), 89-96.
[PMID: 25409419]
Lan, D.; Shen, X.; Yuan, W.; Zhou, Y.; Huang, Q. Sumoylation of PPARγ contributes to vascular endothelium insulin resistance through stabilizing the PPARγ-NcoR complex. J. Cell. Physiol., 2019, 234(11), 19663-19674.
[] [PMID: 30982983]
Li, H.; Zhu, X.; Wang, A.; Wang, G.; Zhang, Y. Co-effect of insulin resistance and biomarkers of inflammation and endothelial dysfunction on hypertension. Hypertens. Res., 2012, 35(5), 513-517.
[] [PMID: 22278626]
Yaribeygi, H.; Atkin, S.L.; Sahebkar, A. A review of the molecular mechanisms of hyperglycemia-induced free radical generation leading to oxidative stress. J. Cell. Physiol., 2019, 234(2), 1300-1312.
[] [PMID: 30146696]
Yaribeygi, H.; Butler, A.E.; Barreto, G.E.; Sahebkar, A. Antioxidative potential of antidiabetic agents: A possible protective mechanism against vascular complications in diabetic patients. J. Cell. Physiol., 2019, 234(3), 2436-2446.
[] [PMID: 30191997]
Yaribeygi, H.; Sathyapalan, T.; Atkin, S.L.; Sahebkar, A. Molecular mechanisms linking oxidative stress and diabetes mellitus. Oxid. Med. Cell. Longev., 2020, 2020, 8609213.
Katakami, N. Mechanism of development of atherosclerosis and cardiovascular disease in diabetes mellitus. J. Atheroscler. Thromb., 2017, 2017, RV17014.
[PMID: 28966336]
Yuan, W.; Ma, C.; Zhou, Y.; Wang, M.; Zeng, G.; Huang, Q. Negative regulation of eNOS-NO signaling by over-SUMOylation of PPARγ contributes to insulin resistance and dysfunction of vascular endothelium in rats. Vascul. Pharmacol., 2019, 122-123, 106597.
[] [PMID: 31479752]
Kampmann, U.; Christensen, B.; Nielsen, T.S.; Pedersen, S.B.; Ørskov, L.; Lund, S.; Møller, N.; Jessen, N. GLUT4 and UBC9 protein expression is reduced in muscle from type 2 diabetic patients with severe insulin resistance. PLoS One, 2011, 6(11), e27854.
[] [PMID: 22114711]
Sakamoto, K.; Holman, G.D. Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic. Am. J. Physiol. Endocrinol. Metab., 2008, 295(1), E29-E37.
[] [PMID: 18477703]
Shi, J.; Kandror, K.V. Sortilin is essential and sufficient for the formation of Glut4 storage vesicles in 3T3-L1 adipocytes. Dev. Cell, 2005, 9(1), 99-108.
[] [PMID: 15992544]
Giorgino, F.; de Robertis, O.; Laviola, L.; Montrone, C.; Perrini, S.; McCowen, K.C.; Smith, R.J. The sentrin-conjugating enzyme mUbc9 interacts with GLUT4 and GLUT1 glucose transporters and regulates transporter levels in skeletal muscle cells. Proc. Natl. Acad. Sci. USA, 2000, 97(3), 1125-1130.
[] [PMID: 10655495]
Liu, L-B.; Omata, W.; Kojima, I.; Shibata, H. The SUMO conjugating enzyme Ubc9 is a regulator of GLUT4 turnover and targeting to the insulin-responsive storage compartment in 3T3-L1 adipocytes. Diabetes, 2007, 56(8), 1977-1985.
[] [PMID: 17536066]
Carmichael, R.E.; Wilkinson, K.A.; Craig, T.J. Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes. Sci. Rep., 2019, 9(1), 6477.
[] [PMID: 31019221]
Baeuerle, P.A.; Baltimore, D. NF-κ B: Ten years after. Cell, 1996, 87(1), 13-20.
[] [PMID: 8858144]
Beg, A.A.; Ruben, S.M.; Scheinman, R.I.; Haskill, S.; Rosen, C.A.; Baldwin, A.S., Jr I kappa B interacts with the nuclear localization sequences of the subunits of NF-kappa B: A mechanism for cytoplasmic retention. Genes Dev., 1992, 6(10), 1899-1913.
[] [PMID: 1340770]
Feldmann, M.; Andreakos, E.; Smith, C.; Bondeson, J.; Yoshimura, S.; Kiriakidis, S.; Monaco, C.; Gasparini, C.; Sacre, S.; Lundberg, A.; Paleolog, E.; Horwood, N.J.; Brennan, F.M.; Foxwell, B.M. Is NF-kappaB a useful therapeutic target in rheumatoid arthritis? Ann. Rheum. Dis., 2002, 61(Suppl. 2), ii13-ii18.
[] [PMID: 12379614]
Hwang, K.W.; Won, T.J.; Kim, H.; Chun, H.J.; Chun, T.; Park, Y. Characterization of the regulatory roles of the SUMO. Diabetes Metab. Res. Rev., 2011, 27(8), 854-861.
[] [PMID: 22069273]
Shao, L.; Zhou, H.J.; Zhang, H.; Qin, L.; Hwa, J.; Yun, Z.; Ji, W.; Min, W. SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression. Nat. Commun., 2015, 6(1), 8917.
[] [PMID: 26596471]
Rawshani, A.; Rawshani, A.; Franzén, S.; Sattar, N.; Eliasson, B.; Svensson, A-M.; Zethelius, B.; Miftaraj, M.; McGuire, D.K.; Rosengren, A.; Gudbjörnsdottir, S. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med., 2018, 379(7), 633-644.
[] [PMID: 30110583]
Bowman, L.; Mafham, M.; Wallendszus, K.; Stevens, W.; Buck, G.; Barton, J.; Murphy, K.; Aung, T.; Haynes, R.; Cox, J.; Murawska, A.; Young, A.; Lay, M.; Chen, F.; Sammons, E.; Waters, E.; Adler, A.; Bodansky, J.; Farmer, A.; McPherson, R.; Neil, A.; Simpson, D.; Peto, R.; Baigent, C.; Collins, R.; Parish, S.; Armitage, J. Effects of aspirin for primary prevention in persons with diabetes mellitus. N. Engl. J. Med., 2018, 379(16), 1529-1539.
[] [PMID: 30146931]
Hölscher, M.E.; Bode, C.; Bugger, H. Diabetic cardiomyopathy: Does the type of diabetes matter? Int. J. Mol. Sci., 2016, 17(12), 2136.
[] [PMID: 27999359]
Li, J.; Zhu, H.; Shen, E.; Wan, L.; Arnold, J.M.O.; Peng, T. Deficiency of rac1 blocks NADPH oxidase activation, inhibits endoplasmic reticulum stress, and reduces myocardial remodeling in a mouse model of type 1 diabetes. Diabetes, 2010, 59(8), 2033-2042.
[] [PMID: 20522592]
Yang, L.; Zhao, D.; Ren, J.; Yang, J. Endoplasmic reticulum stress and protein quality control in diabetic cardiomyopathy. Biochim. Biophys. Acta, 2015, 1852(2), 209-218.
[] [PMID: 24846717]
Wang, T.; Wu, J.; Dong, W.; Wang, M.; Zhong, X.; Zhang, W. The MEK inhibitor U0126 ameliorates diabetic cardiomyopathy by restricting Xbp1’s phosphorylation dependent SUMOylation. Int. J. Biol. Sci., 2021, 17(12), 2984-2999.
Lee, A-H.; Heidtman, K.; Hotamisligil, G.S.; Glimcher, L.H. Dual and opposing roles of the unfolded protein response regulated by IRE1α and XBP1 in proinsulin processing and insulin secretion. Proc. Natl. Acad. Sci. USA, 2011, 108(21), 8885-8890.
[] [PMID: 21555585]
Maralani, G.H.; Tai, B.C.; Wong, T.Y.; Tai, E.S.; Li, J.; Wang, J.J.; Mitchell, P. Metabolic syndrome and risk of age-related cataract over time: An analysis of interval-censored data using a random-effects model. Invest. Ophthalmol. Vis. Sci., 2013, 54(1), 641-646.
[] [PMID: 23258144]
Tan, N.C.; Barbier, S.; Lim, W.Y.; Chia, K.S. 5-Year longitudinal study of determinants of glycemic control for multi-ethnic Asian patients with type 2 diabetes mellitus managed in primary care. Diabetes Res. Clin. Pract., 2015, 110(2), 218-223.
[] [PMID: 26385596]
Lee, Y.J.; Bernstock, J.D.; Nagaraja, N.; Ko, B.; Hallenbeck, J.M. Global SUMOylation facilitates the multimodal neuroprotection afforded by quercetin against the deleterious effects of oxygen/glucose deprivation and the restoration of oxygen/glucose. J. Neurochem., 2016, 138(1), 101-116.
[] [PMID: 27087120]
Wang, T.; Xu, W.; Qin, M.; Yang, Y.; Bao, P.; Shen, F.; Zhang, Z.; Xu, J. Pathogenic mutations in the valosin-containing protein/p97 (VCP) N-domain inhibit the SUMOylation of VCP and lead to impaired stress response. J. Biol. Chem., 2016, 291(27), 14373-14384.
[] [PMID: 27226613]
Ding, Y-W.; Zhao, G-J.; Li, X-L.; Hong, G-L.; Li, M-F.; Qiu, Q-M.; Wu, B.; Lu, Z.Q. SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro. Int. J. Mol. Med., 2016, 37(4), 1049-1058.
[] [PMID: 26935021]
Li, S.; Zhao, G.; Chen, L.; Ding, Y.; Lian, J.; Hong, G.; Lu, Z. Resveratrol protects mice from paraquat-induced lung injury: The important role of SIRT1 and NRF2 antioxidant pathways. Mol. Med. Rep., 2016, 13(2), 1833-1838.
[] [PMID: 26708779]
Akyol, S.; Ugurcu, V.; Balci, M.; Gurel, A.; Erden, G.; Cakmak, O.; Akyol, O. Caffeic acid phenethyl ester: Its protective role against certain major eye diseases. J. Ocul. Pharmacol. Ther., 2014, 30(9), 700-708.
[] [PMID: 25100535]
Nambu, H.; Kubo, E.; Takamura, Y.; Tsuzuki, S.; Tamura, M.; Akagi, Y. Attenuation of aldose reductase gene suppresses high-glucose-induced apoptosis and oxidative stress in rat lens epithelial cells. Diabetes Res. Clin. Pract., 2008, 82(1), 18-24.
[] [PMID: 18835019]
Kim, J.; Kim, C-S.; Sohn, E.; Kim, H.; Jeong, I-H.; Kim, J.S. Lens epithelial cell apoptosis initiates diabetic cataractogenesis in the Zucker diabetic fatty rat. Graefes Arch. Clin. Exp. Ophthalmol., 2010, 248(6), 811-818.
[] [PMID: 20162295]
Han, X.; Dong, X-X.; Shi, M-Y.; Feng, L.; Wang, X-L.; Zhang, J-S.; Yan, Q.C. SUMOylation and deacetylation affect NF-κB p65 activity induced by high glucose in human lens epithelial cells. Int. J. Ophthalmol., 2019, 12(9), 1371-1379.
[] [PMID: 31544029]
Mensah-Brown, E.; Shahin, A.; Parekh, K.; Hakim, A.A.; Shamisi, M.A.; Hsu, D.K.; Lukic, M.L. Functional capacity of macrophages determines the induction of type 1 diabetes. Ann. N. Y. Acad. Sci., 2006, 1084(1), 49-57.
[] [PMID: 17151292]
Padgett, L.E.; Burg, A.R.; Lei, W.; Tse, H.M. Loss of NADPH oxidase-derived superoxide skews macrophage phenotypes to delay type 1 diabetes. Diabetes, 2015, 64(3), 937-946.
[] [PMID: 25288672]
Parsa, R.; Andresen, P.; Gillett, A.; Mia, S.; Zhang, X-M.; Mayans, S.; Holmberg, D.; Harris, R.A. Adoptive transfer of immunomodulatory M2 macrophages prevents type 1 diabetes in NOD mice. Diabetes, 2012, 61(11), 2881-2892.
[] [PMID: 22745325]
Espinoza-Jiménez, A; De Haro, R; Terrazas, LI Taenia crassiceps antigens control experimental type 1 diabetes by inducing alternatively activated macrophages. Mediat. Inflam., 2017, 2017, 8074329.
Wang, F.; Sun, F.; Luo, J.; Yue, T.; Chen, L.; Zhou, H.; Zhang, J.; Yang, C.; Luo, X.; Zhou, Q.; Zhu, H.; Li, J.; Yang, P.; Xiong, F.; Yu, Q.; Zhang, H.; Zhang, W.; Xu, A.; Zhou, Z.; Lu, Q.; Eizirik, D.L.; Zhang, S.; Wang, C.Y. Loss of ubiquitin-conjugating enzyme E2 (Ubc9) in macrophages exacerbates multiple low-dose streptozotocin-induced diabetes by attenuating M2 macrophage polarization. Cell Death Dis., 2019, 10(12), 892.
[] [PMID: 31767832]
Patel, S.; Srivastava, S.; Singh, M.R.; Singh, D. Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomed. Pharmacother., 2019, 112, 108615.
[] [PMID: 30784919]
Wang, B.S.; Ma, X.F.; Zhang, C.Y.; Li, Y.X.; Liu, X.Z.; Hu, C.Q.; Astragaloside, I.V. Astragaloside IV improves angiogenesis and promotes wound healing in diabetic rats via the activation of the SUMOylation pathway. Biomed. Environ. Sci., 2021, 34(2), 124-129.
[] [PMID: 33685571]
Leavenworth, JW; Ma, X; Mo, Y-y; Pauza, ME SUMO conjugation contributes to immune deviation in nonobese diabetic mice by suppressing c-Maf transactivation of IL-4. J. Immunol., 2009, 0803671.
Hsu, C-Y.; Yeh, L-T.; Fu, S-H.; Chien, M-W.; Liu, Y-W.; Miaw, S-C.; Chang, D.M.; Sytwu, H.K. SUMO-defective c-Maf preferentially transactivates Il21 to exacerbate autoimmune diabetes. J. Clin. Invest., 2018, 128(9), 3779-3793.
[] [PMID: 30059018]
Li, Y.Y.; Wang, H.; Yang, X.X.; Geng, H.Y.; Gong, G.; Kim, H.J.; Zhou, Y.H.; Wu, J.J. Small ubiquitin-like modifier 4 (SUMO4) gene M55V polymorphism and type 2 diabetes mellitus: A meta-analysis including 6,823 subjects. Front. Endocrinol. (Lausanne), 2017, 8, 303.
[] [PMID: 29163370]
Schmid, H.; Boucherot, A.; Yasuda, Y.; Henger, A.; Brunner, B.; Eichinger, F.; Nitsche, A.; Kiss, E.; Bleich, M.; Gröne, H.J.; Nelson, P.J.; Schlöndorff, D.; Cohen, C.D.; Kretzler, M. Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy. Diabetes, 2006, 55(11), 2993-3003.
[] [PMID: 17065335]
Maedler, K.; Sergeev, P.; Ris, F.; Oberholzer, J.; Joller- Jemelka, H.I.; Spinas, G.A.; Kaiser, N.; Halban, P.A.; Donath, M.Y. Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets. J. Clin. Invest., 2002, 110(6), 851-860.
[] [PMID: 12235117]
Guo, D.; Li, M.; Zhang, Y.; Yang, P.; Eckenrode, S.; Hopkins, D.; Zheng, W.; Purohit, S.; Podolsky, R.H.; Muir, A.; Wang, J.; Dong, Z.; Brusko, T.; Atkinson, M.; Pozzilli, P.; Zeidler, A.; Raffel, L.J.; Jacob, C.O.; Park, Y.; Serrano-Rios, M.; Larrad, M.T.; Zhang, Z.; Garchon, H.J.; Bach, J.F.; Rotter, J.I.; She, J.X.; Wang, C.Y. A functional variant of SUMO4, a new I κ B α modifier, is associated with type 1 diabetes. Nat. Genet., 2004, 36(8), 837-841.
[] [PMID: 15247916]
Yaribeygi, H.; Atkin, S.L.; Pirro, M.; Sahebkar, A. A review of the anti-inflammatory properties of antidiabetic agents providing protective effects against vascular complications in diabetes. J. Cell. Physiol., 2019, 234(6), 8286-8294.
[] [PMID: 30417367]
Yaribeygi, H.; Katsiki, N.; Butler, A.E.; Sahebkar, A. Effects of antidiabetic drugs on NLRP3 inflammasome activity, with a focus on diabetic kidneys. Drug Discov. Today, 2019, 24(1), 256-262.
[] [PMID: 30086405]
Yaribeygi, H.; Maleki, M.; Sathyapalan, T.; Jamialahmadi, T.; Sahebkar, A. Anti-inflammatory potentials of incretin-based therapies used in the management of diabetes. Life Sci., 2020, 241, 117152.
[] [PMID: 31837333]
Ji, Z.; Dai, J.; Xu, Y. Association between small ubiquitin- like modifier 4 M55V polymorphism with type 2 diabetes and related factors. Chin. J. Diabetes Mellitus., 2010, 2(5), 288-295.
Sinha, N.; Yadav, A.K.; Kumar, V.; Dutta, P.; Bhansali, A.; Jha, V. SUMO4 163 G>A variation is associated with kidney disease in Indian subjects with type 2 diabetes. Mol. Biol. Rep., 2016, 43(5), 345-348.
[] [PMID: 27055882]
Fallah, S.; Jafarzadeh, M.; Hedayati, M. No association of the SUMO4 polymorphism M55V variant in type 2 diabetes in Iranian subjects. Diabetes Res. Clin. Pract., 2010, 90(2), 191-195.
[] [PMID: 20728233]
Owerbach, D.; Piña, L.; Gabbay, K.H. A 212-kb region on chromosome 6q25 containing the TAB2 gene is associated with susceptibility to type 1 diabetes. Diabetes, 2004, 53(7), 1890-1893.
[] [PMID: 15220215]
Noso, S.; Ikegami, H.; Fujisawa, T.; Kawabata, Y.; Asano, K.; Hiromine, Y.; Sugihara, S.; Lee, I.; Kawasaki, E.; Awata, T.; Ogihara, T. Association of SUMO4, as a candidate gene for IDDM5, with susceptibility to type 1 diabetes in Asian populations. Ann. N. Y. Acad. Sci., 2006, 1079(1), 41-46.
[] [PMID: 17130530]
Bohren, K.M.; Nadkarni, V.; Song, J.H.; Gabbay, K.H.; Owerbach, D. A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J. Biol. Chem., 2004, 279(26), 27233-27238.
[] [PMID: 15123604]
Li, M.; Guo, D.; Isales, C.M.; Eizirik, D.L.; Atkinson, M.; She, J-X.; Wang, C.Y. SUMO wrestling with type 1 diabetes. J. Mol. Med. (Berl.), 2005, 83(7), 504-513.
[] [PMID: 15806321]
Qu, H.; Bharaj, B.; Liu, X-Q.; Curtis, J.A.; Newhook, L.A.; Paterson, A.D.; Hudson, T.J.; Polychronakos, C. Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes. Nat. Genet., 2005, 37(2), 111-112.
[] [PMID: 15678135]
Park, G.; Kim, H-S.; Choe, J-Y.; Kim, S-K. SUMO4 C438T polymorphism is associated with papulopustular skin lesion in Korean patients with Behçet’s disease. Rheumatol. Int., 2012, 32(10), 3031-3037.
[] [PMID: 21901353]
Noso, S.; Ikegami, H.; Fujisawa, T.; Kawabata, Y.; Asano, K.; Hiromine, Y.; Tsurumaru, M.; Sugihara, S.; Lee, I.; Kawasaki, E.; Awata, T.; Ogihara, T. Genetic heterogeneity in association of the SUMO4 M55V variant with susceptibility to type 1 diabetes. Diabetes, 2005, 54(12), 3582-3586.
[] [PMID: 16306380]
Sang, Y.; Zong, W.; Liu, M.; Yan, J. Association of SUMO4 M55V polymorphism with type 1 diabetes in Chinese children. J. Pediatr. Endocrinol. Metab., 2010, 23(10), 1083-1086.
[] [PMID: 21158221]
Song, G.G.; Choi, S.J.; Ji, J.D.; Lee, Y.H. Association between the SUMO4 M55V (A163G) polymorphism and susceptibility to type 1 diabetes: A meta-analysis. Hum. Immunol., 2012, 73(10), 1055-1059.
[] [PMID: 22884980]
Sedimbi, S.K.; Luo, X.R.; Sanjeevi, C.B.; Lernmark, A.; Landin-Olsson, M.; Arnqvist, H.; Björck, E.; Nyström, L.; Ohlson, L.O.; Scherstén, B.; Ostman, J.; Aili, M.; Bååth, L.E.; Carlsson, E.; Edenwall, H.; Forsander, G.; Granström, B.W.; Gustavsson, I.; Hanås, R.; Hellenberg, L.; Hellgren, H.; Holmberg, E.; Hörnell, H.; Ivarsson, S.A.; Johansson, C.; Jonsell, G.; Kockum, K.; Lindblad, B.; Lindh, A.; Ludvigsson, J.; Myrdal, U.; Neiderud, J.; Segnestam, K.; Sjöblad, S.; Skogsberg, L.; Strömberg, L.; Ståhle, U.; Thalme, B.; Tullus, K.; Tuvemo, T.; Wallensteen, M.; Westphal, O.; Dahlquist, G.; Aman, J. SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients. Genes Immun., 2007, 8(6), 518-521.
[] [PMID: 17554341]
Sedimbi, S.K.; Shastry, A.; Park, Y.; Rumba, I.; Sanjeevi, C.B. Association of SUMO4 M55V polymorphism with autoimmune diabetes in Latvian patients. Ann. N. Y. Acad. Sci., 2006, 1079(1), 273-277.
[] [PMID: 17130565]
Caputo, M.; Cerrone, G.E.; Mazza, C.; Cédola, N.; Targovnik, H.M.; Gustavo, D.F. No evidence of association of CTLA-4 -318 C/T, 159 C/T, 3′ STR and SUMO4 163 AG polymorphism with autoimmune diabetes. Immunol. Invest., 2007, 36(3), 259-270.
[] [PMID: 17558709]
Sedimbi, S.K.; Kanungo, A.; Shastry, A.; Park, Y.; Sanjeevi, C.B. No association of SUMO4 M55V with autoimmune diabetes in Asian-Indian patients. Int. J. Immunogenet., 2007, 34(2), 137-142.
[] [PMID: 17373940]
Rudofsky, G., Jr; Schlotterer, A.; Humpert, P.M.; Tafel, J.; Morcos, M.; Nawroth, P.P.; Bierhaus, A.; Hamann, A. A M55V polymorphism in the SUMO4 gene is associated with a reduced prevalence of diabetic retinopathy in patients with Type 1 diabetes. Exp. Clin. Endocrinol. Diabetes, 2008, 116(1), 14-17.
[] [PMID: 17926234]
Becares, N.; Gage, M.C.; Pineda-Torra, I. Posttranslational modifications of lipid-activated nuclear receptors: Focus on metabolism. Endocrinology, 2017, 158(2), 213-225.
[] [PMID: 27925773]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy