{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T20:55:29Z","timestamp":1776286529614,"version":"3.50.1"},"reference-count":103,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,18]],"date-time":"2020-01-18T00:00:00Z","timestamp":1579305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/NEU\/04539\/2013 and UID\/NEU\/04539\/2019, PhD Fellowship SFRH\/BD\/109017\/2015 and PTDC\/SAU-NUT\/31712\/2017, as well as by COMPETE-FEDER funds (POCI-01-0145-FEDER-007440 and POCI-01-0145-FEDER-031712)."],"award-info":[{"award-number":["UID\/NEU\/04539\/2013 and UID\/NEU\/04539\/2019, PhD Fellowship SFRH\/BD\/109017\/2015 and PTDC\/SAU-NUT\/31712\/2017, as well as by COMPETE-FEDER funds (POCI-01-0145-FEDER-007440 and POCI-01-0145-FEDER-031712)."]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious consequences. Microvascular complications of diabetes, namely diabetic peripheral neuropathy (DPN), retinopathy (DR), and nephropathy (DN), are associated with high morbidity rates and a heavy social and economic burden. Currently, available therapeutic options to counter the evolution of diabetic microvascular complications are clearly insufficient, which strongly recommends further research. Animal models are essential tools to dissect the molecular mechanisms underlying disease progression, to unravel new therapeutic targets, as well as to evaluate the efficacy of new drugs and\/or novel therapeutic approaches. However, choosing the best animal model is challenging due to the large number of factors that need to be considered. This is particularly relevant for models induced by dietary modifications, which vary markedly in terms of macronutrient composition. In this article, we revisit the rodent models of diet-induced DPN, DR, and DN, critically comparing the main features of these microvascular complications in humans and the criteria for their diagnosis with the parameters that have been used in preclinical research using rodent models, considering the possible need for factors which can accelerate or aggravate these conditions.<\/jats:p>","DOI":"10.3390\/nu12010250","type":"journal-article","created":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T04:27:09Z","timestamp":1579494429000},"page":"250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7371-1079","authenticated-orcid":false,"given":"In\u00eas","family":"Pregui\u00e7a","sequence":"first","affiliation":[{"name":"Institute of Pharmacology &amp; Experimental Therapeutics, &amp; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8161-5239","authenticated-orcid":false,"given":"Andr\u00e9","family":"Alves","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology &amp; Experimental Therapeutics, &amp; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-9059","authenticated-orcid":false,"given":"Sara","family":"Nunes","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology &amp; Experimental Therapeutics, &amp; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1766-9133","authenticated-orcid":false,"given":"Pedro","family":"Gomes","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology &amp; Experimental Therapeutics, &amp; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Center for Health Technology and Services Research (CINTESIS), University of Porto, 4200-450 Porto, Portugal"}]},{"given":"Rosa","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology &amp; Experimental Therapeutics, &amp; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Sofia D.","family":"Viana","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology &amp; Experimental Therapeutics, &amp; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy, 3046-854 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3401-9554","authenticated-orcid":false,"given":"Fl\u00e1vio","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology &amp; Experimental Therapeutics, &amp; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,18]]},"reference":[{"key":"ref_1","unstructured":"IDF (2019). IDF Diabetes Atlas, The International Diabetes Federation (IDF)."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1016\/S0140-6736(18)33015-0","article-title":"Type 2 diabetes: The urgent need to protect young people","volume":"392","author":"Kasmauski","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.2337\/dbi17-0044","article-title":"Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences","volume":"67","author":"Stehouwer","year":"2018","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.2337\/diacare.26.9.2604","article-title":"Microvascular complications at time of diagnosis of type 2 diabetes are similar among diabetic patients detected by targeted screening and patients newly diagnosed in general practice: The hoorn screening study","volume":"26","author":"Spijkerman","year":"2003","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"i6505","DOI":"10.1136\/bmj.i6505","article-title":"How to prevent the microvascular complications of type 2 diabetes beyond glucose control","volume":"356","author":"Valencia","year":"2017","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1016\/j.bbadis.2018.09.032","article-title":"Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy","volume":"1865","author":"Fernandes","year":"2019","journal-title":"Biochim. Biophys Acta Mol. Basis Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4343","DOI":"10.1210\/jc.2017-01922","article-title":"Diabetic Microvascular Disease: An Endocrine Society Scientific Statement","volume":"102","author":"Barrett","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41598-017-18896-5","article-title":"Combination of high-fat\/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications","volume":"8","author":"Barriere","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_9","first-page":"451","article-title":"Animal models in type 2 diabetes research: An overview","volume":"125","author":"Srinivasan","year":"2007","journal-title":"Indian J. Med. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"122","DOI":"10.4103\/ijpvm.IJPVM_206_17","article-title":"Relationship between Dietary Patterns and Incidence of Type 2 Diabetes","volume":"10","author":"Beigrezaei","year":"2019","journal-title":"Int. J. Prev. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/advances\/nmy002","article-title":"Modeling the Western Diet for Preclinical Investigations","volume":"9","author":"Hintze","year":"2018","journal-title":"Adv. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1007\/s13668-018-0244-z","article-title":"Dietary Fat and Risk for Type 2 Diabetes: A Review of Recent Research","volume":"7","year":"2018","journal-title":"Curr. Nutr. Rep."},{"key":"ref_13","first-page":"65","article-title":"Effect of diet on type 2 diabetes mellitus: A review","volume":"11","author":"Sami","year":"2017","journal-title":"Int. J. Health Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"k2234","DOI":"10.1136\/bmj.k2234","article-title":"Dietary and nutritional approaches for prevention and management of type 2 diabetes","volume":"361","author":"Forouhi","year":"2018","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ddmod.2007.09.004","article-title":"Diet-induced models for obesity and type 2 diabetes","volume":"4","author":"Reuter","year":"2007","journal-title":"Drug Discov. Today Dis. Models"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4067\/S0717-95022014000100046","article-title":"Animal Models of Nutritional Induction of Type 2 Diabetes Mellitus","volume":"32","author":"Sarmento","year":"2014","journal-title":"Int. J. Morphol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1038\/s41366-019-0363-7","article-title":"Use of high-fat diets to study rodent obesity as a model of human obesity","volume":"43","author":"Speakman","year":"2019","journal-title":"Int. J. Obes."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s11892-019-1212-8","article-title":"Epidemiology of Peripheral Neuropathy and Lower Extremity Disease in Diabetes","volume":"19","author":"Hicks","year":"2019","journal-title":"Curr. Diabetes Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/dmrr.1226","article-title":"Diabetic polyneuropathies: Update on research definition, diagnostic criteria and estimation of severity","volume":"27","author":"Dyck","year":"2011","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1212\/WNL.60.1.108","article-title":"The spectrum of neuropathy in diabetes and impaired glucose tolerance","volume":"60","author":"Sumner","year":"2003","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/ilar\/ilt052","article-title":"Mouse models of diabetic neuropathy","volume":"54","author":"Sakowski","year":"2014","journal-title":"ILAR J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.2337\/dc10-1303","article-title":"Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments","volume":"33","author":"Tesfaye","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.7748\/ns.3.22.25.s46","article-title":"King\u2019s Fund nursing development","volume":"3","author":"Salvage","year":"1989","journal-title":"Nurs. Stand."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.3389\/fnins.2018.01038","article-title":"Functional and Structural Changes of the Blood-Nerve-Barrier in Diabetic Neuropathy","volume":"12","author":"Richner","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1007\/s00125-019-4959-1","article-title":"New insights into the mechanisms of diabetic complications: Role of lipids and lipid metabolism","volume":"62","author":"Eid","year":"2019","journal-title":"Diabetologia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ejphar.2013.07.017","article-title":"Pathogenesis of diabetic neuropathy: Focus on neurovascular mechanisms","volume":"719","author":"Cotter","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"956","DOI":"10.2337\/diacare.28.4.956","article-title":"Diabetic neuropathies: A statement by the American Diabetes Association","volume":"28","author":"Boulton","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"255","DOI":"10.4093\/dmj.2018.0056","article-title":"Diagnosing Diabetic Neuropathy: Something Old, Something New","volume":"42","author":"Petropoulos","year":"2018","journal-title":"Diabetes Metab. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/jns5.12072","article-title":"Phenotyping animal models of diabetic neuropathy: A consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab)","volume":"19","author":"Biessels","year":"2014","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1007\/s001250051376","article-title":"A comparison of diabetic polyneuropathy in type II diabetic BBZDR\/Wor rats and in type I diabetic BB\/Wor rats","volume":"43","author":"Sima","year":"2000","journal-title":"Diabetologia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jcjd.2016.09.006","article-title":"Inhibition of Adenylyl Cyclase in the Spinal Cord Alleviates Painful Diabetic Neuropathy in Zucker Diabetic Fatty Rats","volume":"41","author":"Feng","year":"2017","journal-title":"Can. J. Diabetes"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13098-019-0433-y","article-title":"Therapeutic effects of stem cells from human exfoliated deciduous teeth on diabetic peripheral neuropathy","volume":"11","author":"Xie","year":"2019","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fan, B., Li, C., Szalad, A., Wang, L., Pan, W., Zhang, R., Chopp, M., Zhang, Z.G., and Liu, X.S. (2019). Mesenchymal stromal cell-derived exosomes ameliorate peripheral neuropathy in a mouse model of diabetes. Diabetologia.","DOI":"10.1007\/s00125-019-05043-0"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17678","DOI":"10.1038\/s41598-018-36098-5","article-title":"Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral Neuropathy","volume":"8","author":"McGregor","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.nbd.2014.10.015","article-title":"BTBR ob\/ob mice as a novel diabetic neuropathy model: Neurological characterization and gene expression analyses","volume":"73","author":"Hur","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/jdi.12650","article-title":"Peripheral neuropathy in prediabetes and the metabolic syndrome","volume":"8","author":"Stino","year":"2017","journal-title":"J. Diabetes Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.diabres.2018.10.020","article-title":"Deep phenotyping neuropathy: An underestimated complication in patients with pre-diabetes and type 2 diabetes associated with albuminuria","volume":"146","author":"Kopf","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1529-8027.2009.00237.x","article-title":"Hyperlipidemia: A new therapeutic target for diabetic neuropathy","volume":"14","author":"Vincent","year":"2009","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.2337\/db09-0047","article-title":"Dyslipidemia-induced neuropathy in mice: The role of oxLDL\/LOX-1","volume":"58","author":"Vincent","year":"2009","journal-title":"Diabetes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.2337\/db06-1176","article-title":"High-fat diet induced neuropathy of pre-diabetes and obesity: Effects of \u201chealthy\u201d diet and aldose reductase inhibition","volume":"56","author":"Obrosova","year":"2007","journal-title":"Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.nbd.2007.07.022","article-title":"Mouse models of diabetic neuropathy","volume":"28","author":"Sullivan","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.neuropharm.2010.09.008","article-title":"Vasopeptidase inhibitor ilepatril (AVE7688) prevents obesity- and diabetes-induced neuropathy in C57Bl\/6J mice","volume":"60","author":"Coppey","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, P.D., Hinder, L.M., Rumora, A.E., Hayes, J.M., Dauch, J.R., Backus, C., Mendelson, F.E., and Feldman, E.L. (2018). Juvenile murine models of prediabetes and type 2 diabetes develop neuropathy. Dis. Model. Mech., 11.","DOI":"10.1242\/dmm.037374"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1111\/jdi.12814","article-title":"Determination of peripheral neuropathy in high-fat diet fed low-dose streptozotocin-treated female C57Bl\/6J mice and Sprague-Dawley rats","volume":"9","author":"Coppey","year":"2018","journal-title":"J. Diabetes Investig."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Xie, F., Fu, H., Hou, J.F., Jiao, K., Costigan, M., and Chen, J. (2013). High energy diets-induced metabolic and prediabetic painful polyneuropathy in rats. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057427"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"326806","DOI":"10.1155\/2012\/326806","article-title":"Effect of Inhibition of Angiotensin-Converting Enzyme and\/or Neutral Endopeptidase on Neuropathy in High-Fat-Fed C57Bl\/6J Mice","volume":"2012","author":"Coppey","year":"2012","journal-title":"J. Obes."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.freeradbiomed.2010.06.016","article-title":"Role of 12\/15-lipoxygenase in nitrosative stress and peripheral prediabetic and diabetic neuropathies","volume":"49","author":"Stavniichuk","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_48","first-page":"717","article-title":"Dietary reversal of neuropathy in a murine model of prediabetes and metabolic syndrome","volume":"10","author":"Hinder","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S0140-6736(09)62124-3","article-title":"Diabetic retinopathy","volume":"376","author":"Cheung","year":"2010","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"546","DOI":"10.4103\/2230-8210.183480","article-title":"Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum?","volume":"20","author":"Chawla","year":"2016","journal-title":"Indian J Endocrinol Metab"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1900\/RDS.2015.12.159","article-title":"Biomarkers in Diabetic Retinopathy","volume":"12","author":"Jenkins","year":"2015","journal-title":"Rev. Diabet. Stud."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1007\/s00592-019-01410-w","article-title":"Widefield optical coherence tomography angiography in diabetic retinopathy","volume":"56","author":"Mastropasqua","year":"2019","journal-title":"Acta Diabetol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1136\/bjo.62.6.351","article-title":"Pathophysiology of diabetic retinopathy","volume":"62","year":"1978","journal-title":"Br. J. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"820","DOI":"10.3389\/fphys.2018.00820","article-title":"Sweet Stress: Coping With Vascular Dysfunction in Diabetic Retinopathy","volume":"9","author":"Santiago","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40662-015-0026-2","article-title":"Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss","volume":"2","author":"Lee","year":"2015","journal-title":"Eye Vis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8166","DOI":"10.1167\/iovs.15-18093","article-title":"Erythropoietin Protects Retinal Cells in Diabetic Rats Through Upregulating ZnT8 via Activating ERK Pathway and Inhibiting HIF-1alpha Expression","volume":"56","author":"Xu","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1242\/dmm.009597","article-title":"Update on animal models of diabetic retinopathy: From molecular approaches to mice and higher mammals","volume":"5","author":"Robinson","year":"2012","journal-title":"Dis. Model. Mech."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11892-017-0913-0","article-title":"Animal Models of Diabetic Retinopathy","volume":"17","author":"Olivares","year":"2017","journal-title":"Curr. Diabetes Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13024-018-0295-z","article-title":"GSK3beta-mediated tau hyperphosphorylation triggers diabetic retinal neurodegeneration by disrupting synaptic and mitochondrial functions","volume":"13","author":"Zhu","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.2337\/db15-1255","article-title":"Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet-Induced Diabetic Retinopathy","volume":"65","author":"Rajagopal","year":"2016","journal-title":"Diabetes"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14318","DOI":"10.1038\/s41598-018-32553-5","article-title":"Omega-3 from Flaxseed Oil Protects Obese Mice Against Diabetic Retinopathy Through GPR120 Receptor","volume":"8","author":"Datilo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1007\/s00125-019-4838-9","article-title":"Pancreatic kallikrein protects against diabetic retinopathy in KK Cg-A(y)\/J and high-fat diet\/streptozotocin-induced mouse models of type 2 diabetes","volume":"62","author":"Cheng","year":"2019","journal-title":"Diabetologia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.3389\/fphys.2018.01501","article-title":"Compound Danshen Dripping Pill Inhibits Retina Cell Apoptosis in Diabetic Rats","volume":"9","author":"Zhang","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"61350","DOI":"10.18632\/oncotarget.18134","article-title":"Thioredoxin plays a key role in retinal neuropathy prior to endothelial damage in diabetic mice","volume":"8","author":"Ren","year":"2017","journal-title":"Oncotarget"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1081\/JDI-100100882","article-title":"Renal function and structure in diabetic, hypertensive, obese ZDFxSHHF-hybrid rats","volume":"22","author":"Tofovic","year":"2000","journal-title":"Ren. Fail."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1530\/JOE-11-0122","article-title":"Diabetic nephropathy and long-term treatment effects of rosiglitazone and enalapril in obese ZSF1 rats","volume":"210","author":"Bilan","year":"2011","journal-title":"J. Endocrinol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11922","DOI":"10.1038\/s41598-018-29812-w","article-title":"Resistance to retinopathy development in obese, diabetic and hypertensive ZSF1 rats: An exciting model to identify protective genes","volume":"8","author":"Caolo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nrneph.2016.163","article-title":"The global burden of chronic kidney disease: Estimates, variability and pitfalls","volume":"13","author":"Glassock","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0140-6736(13)60687-X","article-title":"Chronic kidney disease: Global dimension and perspectives","volume":"382","author":"Jha","year":"2013","journal-title":"Lancet"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.vph.2013.01.001","article-title":"Molecular mechanisms in the pathogenesis of diabetic nephropathy: An update","volume":"58","author":"Arora","year":"2013","journal-title":"Vascul. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2337\/diacare.28.1.164","article-title":"Diabetic nephropathy: Diagnosis, prevention, and treatment","volume":"28","author":"Gross","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_72","first-page":"15","article-title":"Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease","volume":"3","author":"Nazar","year":"2014","journal-title":"J. Nephropharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2147\/IJNRD.S103784","article-title":"Rodent models of diabetic nephropathy: Their utility and limitations","volume":"9","author":"Kitada","year":"2016","journal-title":"Int. J. Nephrol. Renovasc. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1681\/ASN.2010010010","article-title":"Pathologic classification of diabetic nephropathy","volume":"21","author":"Tervaert","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1681\/ASN.2009070721","article-title":"Mouse models of diabetic nephropathy","volume":"20","author":"Brosius","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"616313","DOI":"10.1155\/2012\/616313","article-title":"New experimental models of diabetic nephropathy in mice models of type 2 diabetes: Efforts to replicate human nephropathy","volume":"2012","author":"Soler","year":"2012","journal-title":"Exp. Diabetes Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s10787-014-0215-y","article-title":"Rodent animal models: From mild to advanced stages of diabetic nephropathy","volume":"22","author":"Kaur","year":"2014","journal-title":"Inflammopharmacology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11892-015-0706-2","article-title":"An Update on the Use of Animal Models in Diabetic Nephropathy Research","volume":"16","author":"Betz","year":"2016","journal-title":"Curr. Diabetes Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/BF02428107","article-title":"Consequences of losing ribonuclease III on the Escherichia coli cell","volume":"144","author":"Apirion","year":"1976","journal-title":"Mol. Gen. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"F118","DOI":"10.1152\/ajprenal.00110.2008","article-title":"Structural and functional changes in the kidneys of high-fat diet-induced obese mice","volume":"296","author":"Deji","year":"2009","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.2147\/DMSO.S211253","article-title":"High-fat diet-induced kidney alterations in rats with metabolic syndrome: Endothelial dysfunction and decreased antioxidant defense","volume":"12","author":"Daliry","year":"2019","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1111\/j.1523-1755.2005.00727.x","article-title":"Kidney involvement in a nongenetic rat model of type 2 diabetes","volume":"68","author":"Danda","year":"2005","journal-title":"Kidney Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.numecd.2005.08.007","article-title":"High-fat diet in low-dose-streptozotocin-treated heminephrectomized rats induces all features of human type 2 diabetic nephropathy: A new rat model of diabetic nephropathy","volume":"16","author":"Sugano","year":"2006","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1681\/ASN.2006080895","article-title":"Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production","volume":"18","author":"Prabhakar","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1159\/000449324","article-title":"Longitudinal Changes in Measured Glomerular Filtration Rate, Renal Fibrosis and Biomarkers in a Rat Model of Type 2 Diabetic Nephropathy","volume":"44","author":"Su","year":"2016","journal-title":"Am. J. Nephrol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Dower, K., Zhao, S., Schlerman, F.J., Savary, L., Campanholle, G., Johnson, B.G., Xi, L., Nguyen, V., Zhan, Y., and Lech, M.P. (2017). High resolution molecular and histological analysis of renal disease progression in ZSF1 fa\/faCP rats, a model of type 2 diabetic nephropathy. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181861"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"F423","DOI":"10.1152\/ajprenal.00124.2006","article-title":"Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats","volume":"292","author":"Tapia","year":"2007","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"F712","DOI":"10.1152\/ajprenal.00433.2009","article-title":"Dietary fructose causes tubulointerstitial injury in the normal rat kidney","volume":"298","author":"Nakayama","year":"2010","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2131\/jts.43.45","article-title":"High fructose diet feeding accelerates diabetic nephropathy in Spontaneously Diabetic Torii (SDT) rats","volume":"43","author":"Toyoda","year":"2018","journal-title":"J. Toxicol. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"976209","DOI":"10.1155\/2013\/976209","article-title":"The spontaneously diabetic torii rat: An animal model of nonobese type 2 diabetes with severe diabetic complications","volume":"2013","author":"Sasase","year":"2013","journal-title":"J. Diabetes Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.bbrc.2012.02.001","article-title":"Fructose induces tubulointerstitial injury in the kidney of mice","volume":"419","author":"Aoyama","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"512","DOI":"10.2337\/diabetes.52.2.512","article-title":"Protein kinase C beta inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension","volume":"52","author":"Kelly","year":"2003","journal-title":"Diabetes"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"538737","DOI":"10.1155\/2014\/538737","article-title":"Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals","volume":"2014","author":"Marques","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"162092","DOI":"10.1155\/2011\/162092","article-title":"Diabetic nephropathy amelioration by a low-dose sitagliptin in an animal model of type 2 diabetes (Zucker diabetic fatty rat)","volume":"2011","author":"Mega","year":"2011","journal-title":"Exp. Diabetes Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/j.1463-1326.2011.01548.x","article-title":"Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the blood-retinal barrier in a type 2 diabetes animal model","volume":"14","author":"Goncalves","year":"2012","journal-title":"Diabetes Obes. Metab."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/ajcn\/86.4.899","article-title":"Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease","volume":"86","author":"Johnson","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1210\/er.2008-0033","article-title":"Hypothesis: Could excessive fructose intake and uric acid cause type 2 diabetes?","volume":"30","author":"Johnson","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_98","unstructured":"American Diabetes Association Task Force for Writing Nutrition Principles, and Recommendations for the Management of Diabetes and Related Complications (2002). American Diabetes Association position statement: Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. J. Am. Diet. Assoc., 102, 109\u2013118."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Shoham, D.A., Durazo-Arvizu, R., Kramer, H., Luke, A., Vupputuri, S., Kshirsagar, A., and Cooper, R.S. (2008). Sugary soda consumption and albuminuria: Results from the National Health and Nutrition Examination Survey, 1999\u20132004. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003431"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1007\/s00125-015-3650-4","article-title":"Fructose and uric acid in diabetic nephropathy","volume":"58","author":"Bjornstad","year":"2015","journal-title":"Diabetologia"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Dissard, R., Klein, J., Caubet, C., Breuil, B., Siwy, J., Hoffman, J., Sicard, L., Ducasse, L., Rascalou, S., and Payre, B. (2013). Long term metabolic syndrome induced by a high fat high fructose diet leads to minimal renal injury in C57BL\/6 mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076703"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nrd2476","article-title":"Therapies for hyperglycaemia-induced diabetic complications: From animal models to clinical trials","volume":"8","author":"Calcutt","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/0026-0495(95)90123-X","article-title":"Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL\/6J and A\/J mice","volume":"44","author":"Surwit","year":"1995","journal-title":"Metabolism"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/250\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:29:47Z","timestamp":1760362187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,18]]},"references-count":103,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["nu12010250"],"URL":"https:\/\/doi.org\/10.3390\/nu12010250","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,18]]}}}