Translational Value of Preclinical Models for Studying Diabetes Mellitus and Associated Complications
Keywords:
diabetes, animal model, alloxan, streptozotocinAbstract
Diabetes is Regarded as a rapidly escalating global health crisis; diabetes mellitus represents a prevalent and complex metabolic ailment. This condition is defined by hyperglycemia, where blood plasma contains excessive glucose levels due to failures in insulin production, its biological function, or a combination of both deficiencies. Throughout history, researchers have relied heavily on animal subjects to investigate the underlying mechanisms of the disease, pinpoint therapeutic targets, and evaluate the efficacy of novel drugs and in vivo procedures. The current article examines the laboratory models utilized to study diabetes and its secondary medical issues. Specifically, we provide a concise overview of how alloxan and streptozotocin are used for chemical induction, alongside their roles in simulating type 1 and type 2 diabetes. Furthermore, we emphasize various experimental frameworks involving diverse animal species.
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Unnikrishnan R, Anjana RM, Mohan V. Diabetes mellitus and its compli-cations in India. Nat Rev Endocrinol. 2016;12(6):357–70
Kharroubi AT, Darwish HM. Diabetes mellitus: the epidemic of the century. World J Diabetes. 2015;6(6):850–67.
Tabish SA. Is diabetes becoming the biggest epidemic of the twenty-first century? Int J Health Sci (Qassim) . 2007;1(2):v–viii.
Rayburn WF. Diagnosis and classification of diabetes mellitus: highlights from the American Diabetes Association. J Reprod Med. 1997;42(9):585–6.
Barnett R. Type 1 diabetes. Lancet. 2018;391(10117):195.
Tomita T. Apoptosis of pancreatic β-cells in Type 1 diabetes. Bosn J Basic Med Sci. 2017;17(3):183–93.
Atkinson MA. The pathogenesis and natural history of type 1 diabetes. Cold Spring Harbor Perspect Med. 2012;2(11):a007641.
Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J. 2012;27(4):269–73.
Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci. 2014;11(11):1185–200.
Kampmann U, Madsen LR, Skajaa GO, Iversen DS, Moeller N, Ovesen P. Gestational diabetes: a clinical update. World J Diabetes. 2015;6(8):1065–72.
King AJ. The use of animal models in diabetes research. Br J Pharmacol. 2012;166(3):877–94.
Rewers M, Ludvigsson J. Environmental risk factors for type 1 diabetes. Lancet. 2016;387(10035):2340–8.
Ndisang JF, Vannacci A, Rastogi S. Insulin resistance, type 1 and type 2 diabetes, and related complications 2017. J Diabetes Res. 2017;2017:1478294.
Al-Goblan AS, Al-Alfi MA, Khan MZ. Mechanism linking diabetes mel-litus and obesity. Diabetes Metab Syndr Obes. 2014;7:587–91.
Mugharbel KM, Al-Mansouri MA. Prevalence of obesity among type 2 diabetic patients in Al-khobar primary health care centers. J Family Community Med. 2003;10(2):49–53.
Ewald N, Hardt PD. Diagnosis and treatment of diabetes mellitus in chronic pancreatitis. World J Gastroenterol. 2013;19(42):7276–81.
Prasad RB, Groop L. Genetics of type 2 diabetes-pitfalls and possibilities. Genes. 2015;6(1):87–123.
Deshpande AD, Harris-Hayes M, Schootman M. Epidemiology of diabe-tes and diabetes-related complications. Phys Ther. 2008;88(11):1254–64.
Ramachandran A, Snehalatha C, Shetty AS, Nanditha A. Trends in preva-lence of diabetes in Asian countries. World J Diabetes. 2012;3(6):110–7.
Kaveeshwar SA, Cornwall J. The current state of diabetes mellitus in India. Australas Med J. 2014;7(1):45–8.
Yesudian CA, Grepstad M, Visintin E, Ferrario A. The economic burden of diabetes in India: a review of the literature. Global Health. 2014;10:80.
Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40–50.
Bommer C, Heesemann E, Sagalova V, Manne-Goehler J, Atun R, Bärnighausen T, et al. The global economic burden of diabetes in adults aged 20–79 years: a cost-of-illness study. Lancet Diabetes Endocrinol. 2017;5(6):423–30.
Roep BO, Atkinson M. Animal models have little to teach us about type 1 diabetes: 1. In support of this proposal. Diabetologia. 2004;47(10):1650–6.
Arndt T, Jörns A, Weiss H, Tiedge M, Hedrich HJ, Lenzen S, et al. A vari-able CD3+ T-cell frequency in peripheral blood lymphocytes associated with type 1 diabetes mellitus development in the LEW.1AR1-iddm rat. PLoS ONE. 2013;8(5):e64305.
Graham ML, Schuurman HJ. Validity of animal models of type 1 diabe-tes, and strategies to enhance their utility in translational research. Eur J Pharmacol. 2015;759:221–30.
Kumar S, Singh R, Vasudeva N, Sharma S. Acute and chronic animal models for the evaluation of anti-diabetic agents. Cardiovasc Diabetol. 2012;11:9.
Chatzigeorgiou A, Halapas A, Kalafatakis K, Kamper E. The use of animal models in the study of diabetes mellitus. Vivo. 2009;23(2):245–58.
Vieira R, Souto SB, Sánchez-López E, Machado AL, Severino P, Jose S, et al. Sugar-lowering drugs for type 2 diabetes mellitus and metabolic syndrome-strategies for in vivo administration: part-II. J Clin Med. 2019;8(9):1332
Rees DA, Alcolado JC. Animal models of diabetes mellitus. Diabetes Med. 2005;22(4):359–70.
Perlman RL. Mouse models of human disease: an evolutionary perspec-tive. Evol Med Public Health. 2016;2016(1):170–6.
Peltonen L, McKusick VA. Genomics and medicine. Dissecting human disease in the postgenomic era. Science. 2001;291(5507):1224–9.
Heydemann A. An Overview of Murine High Fat Diet as a Model for Type 2 Diabetes Mellitus. J Diabetes Res. 2016;2016:2902351.
Islam MS, du Loots T. Experimental rodent models of type 2 diabetes: a review. Methods Find Exp Clin Pharmacol. 2009;31(4):249–61.
Iannaccone PM, Jacob HJ. Rats! Dis Model Mech. 2009;2(5–6):206–10.
Bryda EC. The Mighty Mouse: the impact of rodents on advances in biomedical research. Mo Med. 2013;110(3):207–11.
Skovsø S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. J Diabetes Investig. 2014;5(4):349–58.
Sharma P, Garg A, Garg S, Singh V. Animal model used for experi-mental study of diabetes mellitus: an overview. Asian J Biomat Res. 2016;2:99–110.
Federiuk IF, Casey HM, Quinn MJ, Wood MD, Ward WK. Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route of administration, pitfalls, and insulin treatment. Comp Med. 2004;54(3):252–7.
Ighodaro OM, Adeosun AM, Akinloye OA. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina (Kaunas). 2017;53(6):365–74.
Rohilla A, Ali S. Alloxan induced diabetes: mechanisms and effects. Int J Res Pharm Biomed Sci. 2012;3(2):819–23.
Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51(2):216–26.
Katoh M, Sakurai K, Fujimoto Y. Alloxan radical-induced generation of reactive oxygen species in the reaction system of alloxan with ascor-bate. Yakugaku Zasshi. 2002;122(10):831–9.
Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50(6):537–46.
Eileen DM. Inhibition of DNA repair as a means of increasing the antitumor activity of DNA reactive agents. Adv Drug Deliv Rev. 1997;26(2–3):105–18.
Wu J, Yan LJ. Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell gluco-toxicity. Diabetes Metab Syndr Obes. 2015;8:181–8.
Rakieten N, Rakieten ML, Nadkarni MR. Studies on the diabetogenic action of streptozotocin (NSC-37917). Cancer Chemother Rep. 1963;29:91–8.
Rerup CC. Drugs producing diabetes through damage of the insulin secreting cells. Pharmacol Rev. 1970;22(4):485–518.
Eleazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord. 2013;12(1):60.
Ventura-Sobrevilla J, Boone-Villa VD, Aguilar CN, Román-Ramos R, Vega-Avila E, Campos-Sepúlveda E, et al. Effect of varying dose and administration of streptozotocin on blood sugar in male CD1 mice. Proc West Pharmacol Soc. 2011;54:5–9.
Graham ML, Janecek JL, Kittredge JA, Hering BJ, Schuurman HJ. The streptozotocin-induced diabetic nude mouse model: differences between animals from different sources. Comp Med. 2011;61(4):356–60.
Dufrane D, van Steenberghe M, Guiot Y, Goebbels RM, Saliez A, Gianello P. Streptozotocin-induced diabetes in large animals (pigs/primates): role of GLUT2 transporter and beta-cell plasticity. Transplantation. 2006;81(1):36–45.
Elsner M, Guldbakke B, Tiedge M, Munday R, Lenzen S. Relative impor-tance of transport and alkylation for pancreatic beta-cell toxicity of streptozotocin. Diabetologia. 2000;43(12):1528–33.
Paik SG, Fleischer N, Shin SI. Insulin-dependent diabetes mellitus induced by subdiabetogenic doses of streptozotocin: obligatory role of cell-mediated autoimmune processes. Proc Natl Acad Sci U S A. 1980;77(10):6129–33.
Ellis TM, Atkinson MA. The clinical significance of an autoim-mune response against glutamic acid decarboxylase. Nat Med. 1996;2(2):148–53.
Kanaani J, Diacovo MJ, El-Husseini Ael D, Bredt DS, Baekkeskov S. Palmi-toylation controls trafficking of GAD65 from Golgi membranes to axon-specific endosomes and a Rab5a-dependent pathway to presynaptic clusters. J Cell Sci. 2004;117(Pt 10):2001–13.
Deeds MC, Anderson JM, Armstrong AS, Gastineau DA, Hiddinga HJ, Jahangir A, et al. Single dose streptozotocin-induced diabetes: con-siderations for study design in islet transplantation models. Lab Anim. 2011;45(3):131–40.
Furman BL. Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol. 2015;70:5.47.1-5.47.20.
Thayer TC, Wilson SB, Mathews CE. Use of nonobese diabetic mice to understand human type 1 diabetes. Endocrinol Metab Clin N Am. 2010;39(3):541–61.
Pearson JA, Wong FS, Wen L. The importance of the Non Obese Diabetic (NOD) mouse model in autoimmune diabetes. J Autoimmun. 2016;66:76–88.
Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y. Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu. 1980;29(1):1–13.
Mathews CE. Utility of murine models for the study of spontaneous autoimmune type 1 diabetes. Pediatr Diabetes. 2005;6(3):165–77.
Wallis RH, Wang K, Marandi L, Hsieh E, Ning T, Chao GY, et al. Type 1 dia-betes in the BB rat: a polygenic disease. Diabetes. 2009;58(4):1007–17.
Hartoft-Nielsen ML, Rasmussen AK, Bock T, Feldt-Rasmussen U, Kaas A, Buschard K. Iodine and tri-iodo-thyronine reduce the incidence of type 1 diabetes mellitus in the autoimmune prone BB rats. Autoimmunity. 2009;42(2):131–8.
Holmberg R, Refai E, Höög A, Crooke RM, Graham M, Olivecrona G, et al. Lowering apolipoprotein CIII delays onset of type 1 diabetes. Proc Natl Acad Sci U S A. 2011;108(26):10685–9.
Prins JB, Herberg L, Den Bieman M, van Zutphen LF. Genetic variation within and between lines of diabetes-prone and non-diabetes-prone BB rats; allele distribution of 8 protein markers. Lab Anim. 1991;25(3):207–11.
Mordes JP, Bortell R, Blankenhorn EP, Rossini AA, Greiner DL. Rat models of type 1 diabetes: genetics, environment, and autoimmunity. ILAR J. 2004;45(3):278–91.
Yokoi N, Namae M, Fuse M, Wang HY, Hirata T, Seino S, et al. Establish-ment and characterization of the Komeda diabetes-prone rat as a segregating inbred strain. Exp Anim. 2003;52(4):295–301.
Yokoi N, Hayashi C, Fujiwara Y, Wang HY, Seino S. Genetic reconstitution of autoimmune type 1 diabetes with two major susceptibility genes in the rat. Diabetes. 2007;56(2):506–12.
Komeda K, Noda M, Terao K, Kuzuya N, Kanazawa M, Kanazawa Y. Estab-lishment of two substrains, diabetes-prone and non-diabetic, from Long-Evans Tokushima Lean (LETL) rats. Endocr J. 1998;45(6):737–44.
Yokoi N, Kanazawa M, Kitada K, Tanaka A, Kanazawa Y, Suda S, et al. A non-MHC locus essential for autoimmune type I diabetes in the Kom-eda Diabetes-Prone rat. J Clin Invest. 1997;100(8):2015–21.
Yokoi N, Komeda K, Wang HY, Yano H, Kitada K, Saitoh Y, et al. Cblb is a major susceptibility gene for rat type 1 diabetes mellitus. Nat Genet. 2002;31(4):391–4.
Natori T, Kawano K. The LETL rat: a model for IDDM without lymphope-nia. ILAR J. 1993;35(1):15–8.
Kawano K, Hirashima T, Mori S, Saitoh Y, Kurosumi M, Natori T. New inbred strain of Long-Evans Tokushima lean rats with IDDM without lymphopenia. Diabetes. 1991;40(11):1375–81.
Ishida K, Mizuno A, Min Z, Sano T, Shima K. Which is the primary etiologic event in Otsuka Long-Evans Tokushima Fatty rats, a model of spontaneous non-insulin-dependent diabetes mellitus, insulin resist-ance, or impaired insulin secretion? Metabolism. 1995;44(7):940–5.
Al-Awar A, Kupai K, Veszelka M, Szűcs G, Attieh Z, Murlasits Z, et al. Experimental diabetes mellitus in different animal models. J Diabetes Res. 2016;2016:9051426.
Lenzen S, Tiedge M, Elsner M, Lortz S, Weiss H, Jörns A, et al. The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-depend-ent diabetes mellitus. Diabetologia. 2001;44(9):1189–96.
Jörns A, Günther A, Hedrich HJ, Wedekind D, Tiedge M, Lenzen S. Immune cell infiltration, cytokine expression, and beta-cell apoptosis during the development of type 1 diabetes in the spontaneously diabetic LEW.1AR1/Ztm-iddm rat. Diabetes. 2005;54(7):2041–52
Mordes JP, Guberski DL, Leif JH, Woda BA, Flanagan JF, Greiner DL, et al. LEW.1WR1 rats develop autoimmune diabetes spontaneously and in response to environmental perturbation. Diabetes. 2005;54(9):2727–33.
Arndt T, Jörns A, Hedrich HJ, Lenzen S, Wedekind D. Variable immune cell frequencies in peripheral blood of LEW.1AR1-iddm rats over time compared to other congenic LEW strains. Clin Exp Immunol. 2014;177(1):168–78.
Weiss H, Bleich A, Hedrich HJ, Kölsch B, Elsner M, Jörns A, et al. Genetic analysis of the LEW.1AR1-iddm rat: an animal model for spontaneous diabetes mellitus. Mamm Genome. 2005;16(6):432–41.
Azushima K, Gurley SB, Coffman TM. Modelling diabetic nephropathy in mice. Nat Rev Nephrol. 2018;14(1):48–56.
Kong LL, Wu H, Cui WP, Zhou WH, Luo P, Sun J, et al. Advances in murine models of diabetic nephropathy. J Diabetes Res. 2013;2013:797548.
Todd JA. Intolerable secretion and diabetes in tolerant transgenic mice, revisited. Nat Genet. 2016;48(5):476–7.
Goto Y, Kakizaki M, Masaki N. Production of spontaneous dia-betic rats by repetition of selective breeding. Tohoku J Exp Med. 1976;119(1):85–90.
Movassat J, Calderari S, Fernández E, Martín MA, Escrivá F, Plachot C, et al. Type 2 diabetes—a matter of failing beta-cell neogenesis? Clues from the GK rat model. Diabetes Obes Metab. 2007;9(Suppl 2):187–95.
Portha B. Programmed disorders of beta-cell development and func-tion as one cause for type 2 diabetes? The GK rat paradigm. Diabetes Metab Res Rev. 2005;21(6):495–504.
Portha B, Lacraz G, Kergoat M, Homo-Delarche F, Giroix MH, Bailbé D, et al. The GK rat beta-cell: a prototype for the diseased human beta-cell in type 2 diabetes? Mol Cell Endocrinol. 2009;297(1–2):73–85.
Portha B, Giroix MH, Tourrel-Cuzin C, Le-Stunff H, Movassat J. The GK rat: a prototype for the study of non-overweight type 2 diabetes. Methods Mol Biol. 2012;933:125–59.
Nie J, Xue B, Sukumaran S, Jusko WJ, Dubois DC, Almon RR. Differential muscle gene expression as a function of disease progression in Goto-Kakizaki diabetic rats. Mol Cell Endocrinol. 2011;338(1–2):10–7.
Xue B, Sukumaran S, Nie J, Jusko WJ, Dubois DC, Almon RR. Adipose tis-sue deficiency and chronic inflammation in diabetic Goto-Kakizaki rats. PLoS ONE. 2011;6(2):e17386.
Garnett KE, Chapman P, Chambers JA, Waddell ID, Boam DS. Differential gene expression between Zucker Fatty rats and Zucker Diabetic Fatty rats: a potential role for the immediate-early gene Egr-1 in regulation of beta cell proliferation. J Mol Endocrinol. 2005;35(1):13–25.
Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Res. 2007;125(3):451–72.
Phillips MS, Liu Q, Hammond HA, Dugan V, Hey PJ, Caskey CJ, et al. Leptin receptor missense mutation in the fatty Zucker rat. Nat Genet. 1996;13(1):18–9.
Chen D, Wang MW. Development and application of rodent models for type 2 diabetes. Diabetes Obes Metab. 2005;7(4):307–17.
Slieker LJ, Sundell KL, Heath WF, Osborne HE, Bue J, Manetta J, et al. Glucose transporter levels in tissues of spontaneously diabetic Zucker fa/fa rat (ZDF/drt) and viable yellow mouse (Avy/a). Diabetes. 1992;41(2):187–93.
Wexler BC, Iams SG, McMurtry JP. Pathophysiological differences between obese and non-obese spontaneously hypertensive rats. Br J Exp Pathol. 1980;61(2):195–207.
Koletsky S. Obese spontaneously hypertensive rats–a model for study of atherosclerosis. Exp Mol Pathol. 1973;19(1):53–60.
Tarrés MC, Martinez SM, Montenegro S, Llorens A, Picena JC, Naves A. The eSS rat. A model of non-insulin-dependent human diabetes. Am J Pathol. 1992;141(3):761–3.
Gómez Dumm CL, Semino MC, Gagliardino JJ. Sequential morphologi-cal changes in pancreatic islets of spontaneously diabetic rats. Pancreas. 1990;5(5):533–9.
Hummel KP, Dickie MM, Coleman DL. Diabetes, a new mutation in the mouse. Science. 1966;153(3740):1127–8.
Chen W, Zhou XB, Liu HY, Xu C, Wang LL, Li S. P633H, a novel dual agonist at peroxisome proliferator-activated receptors alpha and gamma, with different anti-diabetic effects in db/db and KK-Ay mice. Br J Pharmacol. 2009;157(5):724–35.
Ikeda H. KK mouse. Diabetes Res Clin Pract. 1994;24(Suppl):S313–6
Berndt A, Sundberg BA, Silva KA, Kennedy VE, Richardson MA, Li Q, et al. Phenotypic characterization of the KK/HlJ inbred mouse strain. Vet Pathol. 2014;51(4):846–57.
Bleisch VR, Mayer J, Dickie MM. Familial diabetes mellitus in mice, asso-ciated with insulin resistance, obesity, and hyperplasia of the islands of langerhans. Am J Pathol. 1952;28(3):369–85.
Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269(5223):543–6.
Leahy JL, Bonner-Weir S, Weir GC. Minimal chronic hyperglycemia is a critical determinant of impaired insulin secretion after an incomplete pancreatectomy. J Clin Invest. 1988;81(5):1407–14.
Bonner-Weir S, Trent DF, Weir GC. Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release. J Clin Invest. 1983;71(6):1544–53.
Yoon JW, London WT, Curfman BL, Brown RL, Notkins AL. Coxsackie virus B4 produces transient diabetes in nonhuman primates. Diabetes. 1986;35(6):712–6.
Guberski DL, Thomas VA, Shek WR, Like AA, Handler ES, Rossini AA, et al. Induction of type I diabetes by Kilham’s rat virus in diabetes-resistant BB/Wor rats. Science. 1991;254(5034):1010–3.
Baek HS, Yoon JW. Direct involvement of macrophages in destruction of beta-cells leading to development of diabetes in virus-infected mice. Diabetes. 1991;40(12):1586–97.
Yoon JW, Austin M, Onodera T, Notkins AL. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med. 1979;300(21):1173–9.
Utsugi T, Kanda T, Tajima Y, Tomono S, Suzuki T, Murata K, et al. A new animal model of non-insulin-dependent diabetes mellitus induced by the NDK25 variant of encephalomyocarditis virus. Diabetes Res. 1992;20(4):109–19.
Meier H, Yerganian G. Spontaneous hereditary diabetes mellitus in the Chinese hamster (Cricetulus griseus). III. Maintenance of a diabetic hamster colony with the aid of hypoglycemic therapy. Diabetes. 1961;10:19–21.
Wise PH, Weir BJ, Hime JM, Forrest E. The diabetic syndrome in the tuco-tuco (Ctenomys talarum). Diabetologia. 1972;8(3):165–72.
Kane JD, Steinbach TJ, Sturdivant RX, Burks RE. Sex-associated effects on hematologic and serum chemistry analytes in sand rats (Psammomys obesus). J Am Assoc Lab Anim Sci. 2012;51(6):769–74.
Ziv E, Shafrir E, Kalman R, Galer S, Bar-On H. Changing pattern of preva-lence of insulin resistance in Psammomys obesus, a model of nutrition-ally induced type 2 diabetes. Metabolism. 1999;48(12):1549–54.
Marquié G, Hadjiisky P, Arnaud O, Duhault J. Development of mac-roangiopathy in sand rats (Psammomys obesus), an animal model of non-insulin-dependent diabetes mellitus: effect of gliclazide. Am J Med. 1991;90(6a):55s–61s.
Matveyenko AV, Butler PC. Islet amyloid polypeptide (IAPP) transgenic rodents as models for type 2 diabetes. ILAR J. 2006;47(3):225–33.
Shafrir E, Ziv E, Kalman R. Nutritionally induced diabetes in desert rodents as models of type 2 diabetes: Acomys cahirinus (spiny mice) and Psammomys obesus (desert gerbil). ILAR J. 2006;47(3):212–24.
Meng X, Zhu F, Chen K. Silkworm: a promising model organism in life science. J Insect Sci. 2017;17(5):97.
International Silkworm Genome Consortium. The genome of a lepidop-teran model insect, the silkworm Bombyx mori. Insect Biochem Mol Biol. 2008;38(12):1036–45.
Zhang X, Xue R, Cao G, Pan Z, Zheng X, Gong C. Silkworms can be used as an animal model to screen and evaluate gouty therapeutic drugs. J Insect Sci. 2012;12:4.
Phillips RW, Panepinto LM, Spangler R, Westmoreland N. Yucatan miniature swine as a model for the study of human diabetes mellitus. Diabetes. 1982;31(Suppl 1 Pt 2):30–6.
Boullion RD, Mokelke EA, Wamhoff BR, Otis CR, Wenzel J, Dixon JL, et al. Porcine model of diabetic dyslipidemia: insulin and feed algorithms for mimicking diabetes mellitus in humans. Comp Med. 2003;53(1):42–52.
Hansen BC, Bodkin NL. Heterogeneity of insulin responses: phases lead-ing to type 2 (non-insulin-dependent) diabetes mellitus in the rhesus monkey. Diabetologia. 1986;29(10):713–9.
Bremer AA, Stanhope KL, Graham JL, Cummings BP, Wang W, Saville BR, et al. Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes. Clin Transl Sci. 2011;4(4):243–52
Zhu H, Yu L, He Y, Wang B. Nonhuman primate models of type 1 diabe-tes mellitus for islet transplantation. J Diabetes Res. 2014;2014:785948.
Den Broeder MJ, Kopylova VA, Kamminga LM, Legler J. Zebrafish as a model to study the role of peroxisome proliferating-activated receptors in Adipogenesis and obesity. PPAR Res. 2015;2015:358029.
Lieschke GJ, Currie PD. Animal models of human disease: zebrafish swim into view. Nat Rev Genet. 2007;8(5):353–67.
Oka T, Nishimura Y, Zang L, Hirano M, Shimada Y, Wang Z, et al. Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity. BMC Physiol. 2010;10:21.
Teame T, Zhang Z, Ran C, Zhang H, Yang Y, Ding Q, et al. The use of zebrafish (Danio rerio) as biomedical models. Anim Front. 2019;9(3):68–77.
Papatheodorou K, Banach M, Bekiari E, Rizzo M, Edmonds M. Complica-tions of diabetes 2017. J Diabetes Res. 2018;2018:3086167.
Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058–70.
Hage Hassan R, Bourron O, Hajduch E. Defect of insulin signal in peripheral tissues: important role of ceramide. World J Diabetes. 2014;5(3):244–57.
Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complica-tions in diabetes mellitus: distinct or continuum? Indian J Endocrinol Metab. 2016;20(4):546–51.
Bansal V, Kalita J, Misra UK. Diabetic neuropathy. Postgrad Med J. 2006;82(964):95–100.
Yagihashi S, Mizukami H, Sugimoto K. Mechanism of diabetic neu-ropathy: where are we now and where to go? J Diabetes Investig. 2011;2(1):18–32.
Jakobsen J, Lundbaek K. Neuropathy in experimental diabetes: an animal model. Br Med J. 1976;2(6030):278–9.
O’Brien PD, Sakowski SA, Feldman EL. Mouse models of diabetic neu-ropathy. ILARJ. 2014;54(3):259–72.
Muthuraman A, Ramesh M, Sood S. Development of animal model for vasculatic neuropathy: induction by ischemic-reperfusion in the rat femoral artery. J Neurosci Methods. 2010;186(2):215–21.
Kennedy WR, Quick DC, Miyoshi T, Gerritsen GC. Peripheral neurology of the diabetic Chinese hamster. Diabetologia. 1982;23(5):445–51.
Cornblath DR, Hillman MA, Striffler JS, Herman CN, Hansen BC. Periph-eral neuropathy in diabetic monkeys. Diabetes. 1989;38(11):1365–70.
Singh VP, Bali A, Singh N, Jaggi AS. Advanced glycation end prod-ucts and diabetic complications. Korean J Physiol Pharmacol. 2014;18(1):1–14.
Reddy MA, Tak Park J, Natarajan R. Epigenetic modifications in the pathogenesis of diabetic nephropathy. Semin Nephrol. 2013;33(4):341–53.
Watanabe Y, Itoh Y, Yoshida F, Koh N, Tamai H, Fukatsu A, et al. Unique glomerular lesion with spontaneous lipid deposition in glomerular capillary lumina in the NON strain of mice. Nephron. 1991;58(2):210–8.
Alpers CE, Hudkins KL. Mouse models of diabetic nephropathy. Curr Opin Nephrol Hypertens. 2011;20(3):278–84.
Janssen U, Riley SG, Vassiliadou A, Floege J, Phillips AO. Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progres-sive nephropathy. Kidney Int. 2003;63(6):2162–70.
Kitada M, Ogura Y, Koya D. Rodent models of diabetic nephropathy: their utility and limitations. Int J Nephrol Renovasc Dis. 2016;9:279–90.
Intine RV, Olsen AS, Sarras MP Jr. A zebrafish model of diabetes mellitus and metabolic memory. J Vis Exp. 2013;72:e50232.
Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther. 2008;88(11):1322–35.
Wang W, Lo ACY. Diabetic retinopathy: pathophysiology and treat-ments. Int J Mol Sci. 2018;19(6):1816
Olivares AM, Althoff K, Chen GF, Wu S, Morrisson MA, DeAngelis MM, et al. Animal models of diabetic retinopathy. Curr Diab Rep. 2017;17(10):93.
Cai X, McGinnis JF. Diabetic retinopathy: animal models, therapies, and perspectives. J Diabetes Res. 2016;2016:3789217.
Lai AKW, Lo ACY. Animal models of diabetic retinopathy: summary and comparison. J Diabetes Res. 2013;2013:106594.
Heckler K, Kroll J. Zebrafish as a model for the study of microvascu-lar complications of diabetes and their mechanisms. Int J Mol Sci. 2017;18(9):2002.
Athithan L, Gulsin GS, McCann GP, Levelt E. Diabetic cardiomyopathy: pathophysiology, theories and evidence to date. World J Diabetes. 2019;10(10):490–510.
Bhatti R, Sharma S, Singh J, Ishar MP. Ameliorative effect of Aegle marmelos leaf extract on early stage alloxan-induced diabetic cardio-myopathy in rats. Pharm Biol. 2011;49(11):1137–43.
Rodrigues B, McNeill JH. Cardiac dysfunction in isolated perfused hearts from spontaneously diabetic BB rats. Can J Physiol Pharmacol. 1990;68(4):514–8.
Bellinger DA, Merricks EP, Nichols TC. Swine models of type 2 diabetes mellitus: insulin resistance, glucose tolerance, and cardiovascular com-plications. ILARJ. 2006;47(3):243–58.
Mizushige K, Yao L, Noma T, Kiyomoto H, Yu Y, Hosomi N, et al. Altera-tion in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model. Circulation. 2000;101(8):899–907.
Ares-Carrasco S, Picatoste B, Benito-Martín A, Zubiri I, Sanz AB, Sánchez-Niño MD, et al. Myocardial fibrosis and apoptosis, but not inflammation, are present in long-term experimental diabetes. Am J Physiol Heart Circ Physiol. 2009;297(6):H2109–19.
Picatoste B, Ramírez E, Caro-Vadillo A, Iborra C, Ares-Carrasco S, Egido J, et al. Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis pri-marily by insulin-dependent mechanisms in experimental type-II dia-betes. Potential roles of GLP-1 isoforms. PLoS ONE. 2013;8(10):e78330.
Gvazava IG, Rogovaya OS, Borisov MA, Vorotelyak EA, Vasiliev AV. Patho-genesis of type 1 diabetes mellitus and rodent experimental models. Acta Naturae. 2018;10(1):24–33.
Wang B, Chandrasekera PC, Pippin JJ. Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes. Curr Diabetes Rev. 2014;10(2):131–45.
Wang YW, Sun GD, Sun J, Liu SJ, Wang J, Xu XH, et al. Spontaneous type 2 diabetic rodent models. J Diabetes Res. 2013;2013:401723.
Lutz TA, Woods SC. Overview of animal models of obesity. Curr Protoc Pharmacol. 2012;58(1):5–61.
Tomino Y. Lessons from the KK-Ay mouse, a spontaneous animal model for the treatment of human type 2 diabetic nephropathy. Nephrourol Mon. 2012;4(3):524–9.
Chen C, Cohrs CM, Stertmann J, Bozsak R, Speier S. Human beta cell mass and function in diabetes: recent advances in knowledge and technologies to understand disease pathogenesis. Mol Metab. 2017;6(9):943–57.
Horwitz MS, Bradley LM, Harbertson J, Krahl T, Lee J, Sarvetnick N. Dia-betes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med. 1998;4(7):781–5.
Filippi CM, von Herrath MG. Viral trigger for type 1 diabetes: pros and cons. Diabetes. 2008;57(11):2863–71
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