Abstract
Diabetes mellitus is a type of metabolic disorders. Various pharmaceutical interventions and animal models have been used to investigate the genetic, environmental, and etiological aspects of diabetes and its effects. In recent years for the development of ant-diabetic remedies, numerous novel genetically modified animals, pharmaceutical substances, medical techniques, viruses, and hormones have been developed to screen diabetic complications. A unique disease-treating drug with new properties is still being sought after. The current review tried to include all published models and cutting-edge techniques. Experimental induction of diabetes mellitus in animal models and in vitro methods are essential for advancing our knowledge, a thorough grasp of pathophysiology, and the creation of novel therapeutics. Animal models and in vitro techniques are necessary to develop innovative diabetic medications. New approaches and additional animal models are required for diabetes research to advance. This is particularly true for models produced via dietary modifications, which have various macronutrient compositions. In this article, we review the rodent models of diet-induced diabetic peripheral neuropathy, diabetic retinopathy, and diabetic nephropathy and critically compare the key characteristics of these micro-vascular complications in humans and the diagnostic criteria with the parameters used in preclinical research using rodent models, taking into consideration the potential need for factors that can accelerate or aggravate these conditions.
[1]
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27(5): 1047-53.
[http://dx.doi.org/10.2337/diacare.27.5.1047] [PMID: 15111519]
[http://dx.doi.org/10.2337/diacare.27.5.1047] [PMID: 15111519]
[2]
Liu JP, Zhang M, Wang WY, Grimsgaard S. Chinese herbal medicines for type 2 diabetes mellitus. Cochrane Database Syst Rev 2004; 2002(3): CD003642.
[PMID: 15266492]
[PMID: 15266492]
[3]
Kumar S, Singh R, Vasudeva N, Sharma S. Acute and chronic animal models for the evaluation of anti-diabetic agents. Cardiovasc Diabetol 2012; 11(1): 9.
[http://dx.doi.org/10.1186/1475-2840-11-9] [PMID: 22257465]
[http://dx.doi.org/10.1186/1475-2840-11-9] [PMID: 22257465]
[4]
Chattopadhyay S, Ramanathan M, Das J, Bhattacharya SK. Animal models in experimental diabetes mellitus. Indian J Exp Biol 1997; 35(11): 1141-5.
[PMID: 9567740]
[PMID: 9567740]
[5]
Chennuru VGS. Rediscovered the induction of diabetogenic agents in the experimental animal model. Int J Appl Biol Pharm Technol 2016; 7(1): 95-104.
[6]
Iranloye BO, Arikawe AP, Rotimi G, Sogbade AO. Anti-diabetic and anti-oxidant effects of Zingiber officinale on alloxan-induced and insulin-resistant diabetic male rats. Niger J Physiol Sci 2011; 26(1): 89-96.
[PMID: 22314994]
[PMID: 22314994]
[7]
Park BH, Rho HW, Park JW, et al. Protective mechanism of glucose against alloxan-induced pancreatic beta-cell damage. Biochem Biophys Res Commun 1995; 210(1): 1-6.
[http://dx.doi.org/10.1006/bbrc.1995.1619] [PMID: 7741727]
[http://dx.doi.org/10.1006/bbrc.1995.1619] [PMID: 7741727]
[8]
Brentjens R, Saltz L. Islet cell tumors of the pancreas: the medical oncologist’s perspective. Surg Clin North Am 2001; 81(3): 527-42.
[http://dx.doi.org/10.1016/S0039-6109(05)70141-9] [PMID: 11459269]
[http://dx.doi.org/10.1016/S0039-6109(05)70141-9] [PMID: 11459269]
[9]
Halim D, Khalifa K, Awadallah R, El-Hawary Z, El-Dessouky EA. Serum mineral changes in dithizone-induced diabetes before and after insulin treatment. Z Ernährungswiss 1977; 16(1): 22-6.
[http://dx.doi.org/10.1007/BF02021207] [PMID: 855379]
[http://dx.doi.org/10.1007/BF02021207] [PMID: 855379]
[10]
Thirone ACP, Scarlett JA, Gasparetti AL, et al. Modulation of growth hormone signal transduction in kidneys of streptozotocin-induced diabetic animals: effect of a growth hormone receptor antagonist. Diabetes 2002; 51(7): 2270-81.
[http://dx.doi.org/10.2337/diabetes.51.7.2270] [PMID: 12086960]
[http://dx.doi.org/10.2337/diabetes.51.7.2270] [PMID: 12086960]
[11]
Campbell J, Chaikof L, Davidson IWF. Metahypophyseal diabetes produced by growth hormone. Endocrinology 1954; 54(1): 48-58.
[http://dx.doi.org/10.1210/endo-54-1-48] [PMID: 13151091]
[http://dx.doi.org/10.1210/endo-54-1-48] [PMID: 13151091]
[12]
Ferris HA, Kahn CR. New mechanisms of glucocorticoid-induced insulin resistance: make no bones about it. J Clin Invest 2012; 122(11): 3854-7.
[http://dx.doi.org/10.1172/JCI66180] [PMID: 23093783]
[http://dx.doi.org/10.1172/JCI66180] [PMID: 23093783]
[13]
Shafrir E. Animal models of non-insulin-dependent diabetes. Diabetes Metab Rev 1992; 8(3): 179-208.
[http://dx.doi.org/10.1002/dmr.5610080302] [PMID: 1292911]
[http://dx.doi.org/10.1002/dmr.5610080302] [PMID: 1292911]
[14]
Bates SH, Kulkarni RN, Seifert M, Myers MG Jr. Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. Cell Metab 2005; 1(3): 169-78.
[http://dx.doi.org/10.1016/j.cmet.2005.02.001] [PMID: 16054060]
[http://dx.doi.org/10.1016/j.cmet.2005.02.001] [PMID: 16054060]
[15]
Bohlen HG, Niggl BA. Arteriolar anatomical and functional abnormalities in juvenile mice with genetic or streptozotocin-induced diabetes mellitus. Circ Res 1979; 45(3): 390-6.
[http://dx.doi.org/10.1161/01.RES.45.3.390] [PMID: 455606]
[http://dx.doi.org/10.1161/01.RES.45.3.390] [PMID: 455606]
[16]
Kebede MA, Attie AD. Insights into obesity and diabetes at the intersection of mouse and human genetics. Trends Endocrinol Metab 2014; 25(10): 493-501.
[http://dx.doi.org/10.1016/j.tem.2014.06.006] [PMID: 25034129]
[http://dx.doi.org/10.1016/j.tem.2014.06.006] [PMID: 25034129]
[17]
Peterson RG, Little LA, Neel MA. WKY Fatty Rat as a Model of Obesity and Non-insulin-dependent Diabetes Mellitus. ILAR J 1990; 32(3): 13-5.
[http://dx.doi.org/10.1093/ilar.32.3.13] [PMID: 34191867]
[http://dx.doi.org/10.1093/ilar.32.3.13] [PMID: 34191867]
[18]
Thorburn AW, Holdsworth A, Proietto J, Morahan G. Differential and genetically separable associations of leptin with obesity-related traits. International journal of obesity and related metabolic disorders 2000; 24(6): 742-50.
[http://dx.doi.org/10.1038/sj.ijo.0801213]
[http://dx.doi.org/10.1038/sj.ijo.0801213]
[19]
Kawano K, Hirashima T, Mori S, Saitoh Y, Kurosumi M, Natori T. Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty (OLETF) strain. Diabetes 1992; 41(11): 1422-8.
[http://dx.doi.org/10.2337/diab.41.11.1422] [PMID: 1397718]
[http://dx.doi.org/10.2337/diab.41.11.1422] [PMID: 1397718]
[20]
Ueda H, Ikegami H, Yamato E, et al. The NSY mouse: a new animal model of spontaneous NIDDM with moderate obesity. Diabetologia 1995; 38(5): 503-8.
[http://dx.doi.org/10.1007/BF00400717] [PMID: 7489831]
[http://dx.doi.org/10.1007/BF00400717] [PMID: 7489831]
[21]
Suzuki W, Iizuka S, Tabuchi M, et al. A new mouse model of spontaneous diabetes derived from ddY strain. Exp Anim 1999; 48(3): 181-9.
[http://dx.doi.org/10.1538/expanim.48.181] [PMID: 10480023]
[http://dx.doi.org/10.1538/expanim.48.181] [PMID: 10480023]
[22]
Kanasaki K, Koya D. Biology of obesity: lessons from animal models of obesity. J Biomed Biotechnol 2011; 2011: 1-11.
[http://dx.doi.org/10.1155/2011/197636] [PMID: 21274264]
[http://dx.doi.org/10.1155/2011/197636] [PMID: 21274264]
[23]
Miralles F, Portha B. Early development of beta-cells is impaired in the GK rat model of type 2 diabetes. Diabetes 2001; 50(1): S84-8.
[http://dx.doi.org/10.2337/diabetes.50.2007.S84] [PMID: 11272209]
[http://dx.doi.org/10.2337/diabetes.50.2007.S84] [PMID: 11272209]
[24]
Sato N, Komatsu K, Kurumatani H. Late onset of diabetic nephropathy in spontaneously diabetic GK rats. Am J Nephrol 2003; 23(5): 334-42.
[http://dx.doi.org/10.1159/000072915] [PMID: 12920324]
[http://dx.doi.org/10.1159/000072915] [PMID: 12920324]
[25]
Miao G, Ito T, Uchikoshi F, et al. Development of islet-like cell clusters after pancreas transplantation in the spontaneously diabetic Torri rat. Am J Transplant 2005; 5(10): 2360-7.
[http://dx.doi.org/10.1111/j.1600-6143.2005.01023.x] [PMID: 16162183]
[http://dx.doi.org/10.1111/j.1600-6143.2005.01023.x] [PMID: 16162183]
[26]
Ohta T, Matsui K, Miyajima K, et al. Effect of insulin therapy on renal changes in spontaneously diabetic Torii rats. Exp Anim 2007; 56(5): 355-62.
[http://dx.doi.org/10.1538/expanim.56.355] [PMID: 18075195]
[http://dx.doi.org/10.1538/expanim.56.355] [PMID: 18075195]
[27]
Choi SB, Park CH, Choi MK, Jun DW, Park S. Improvement of insulin resistance and insulin secretion by water extracts of Cordyceps militaris, Phellinus linteus, and Paecilomyces tenuipes in 90% pancreatectomized rats. Biosci Biotechnol Biochem 2004; 68(11): 2257-64.
[http://dx.doi.org/10.1271/bbb.68.2257] [PMID: 15564662]
[http://dx.doi.org/10.1271/bbb.68.2257] [PMID: 15564662]
[28]
Ramachandran S, Rajasekaran A, Adhirajan N. In vivo and in vitro antidiabetic activity of terminalia paniculata bark: An evaluation of possible phytoconstituents and mechanisms for blood glucose control in diabetes. ISRN Pharmacol 2013; 2013: 1-10.
[http://dx.doi.org/10.1155/2013/484675] [PMID: 23936668]
[http://dx.doi.org/10.1155/2013/484675] [PMID: 23936668]
[29]
Hansotia T, Drucker DJ. GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice. Regul Pept 2005; 128(2): 125-34.
[http://dx.doi.org/10.1016/j.regpep.2004.07.019] [PMID: 15780432]
[http://dx.doi.org/10.1016/j.regpep.2004.07.019] [PMID: 15780432]
[30]
Lelliott C, Vidal-Puig AJ. Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation. International journal of obesity and related metabolic disorders 2004; 28(4): 22-8.
[http://dx.doi.org/10.1038/sj.ijo.0802854]
[http://dx.doi.org/10.1038/sj.ijo.0802854]
[31]
Jarvill-Taylor KJ, Anderson RA, Graves DJ. A hydroxychalcone derived from cinnamon functions as a mimetic for insulin in 3T3-L1 adipocytes. J Am Coll Nutr 2001; 20(4): 327-36.
[http://dx.doi.org/10.1080/07315724.2001.10719053] [PMID: 11506060]
[http://dx.doi.org/10.1080/07315724.2001.10719053] [PMID: 11506060]
[32]
Maddux BA, See W, Lawrence JC Jr, Goldfine AL, Goldfine ID, Evans JL. Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid. Diabetes 2001; 50(2): 404-10.
[http://dx.doi.org/10.2337/diabetes.50.2.404] [PMID: 11272154]
[http://dx.doi.org/10.2337/diabetes.50.2.404] [PMID: 11272154]
[33]
Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet 2010; 376(9735): 124-36.
[http://dx.doi.org/10.1016/S0140-6736(09)62124-3] [PMID: 20580421]
[http://dx.doi.org/10.1016/S0140-6736(09)62124-3] [PMID: 20580421]
[34]
Chawla R, Chawla A, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J Endocrinol Metab 2016; 20(4): 546-51.
[http://dx.doi.org/10.4103/2230-8210.183480] [PMID: 27366724]
[http://dx.doi.org/10.4103/2230-8210.183480] [PMID: 27366724]
[35]
Zhang HM, Dang H, Kamat A, Yeh CK, Zhang BX. Geldanamycin derivative ameliorates high fat diet-induced renal failure in diabetes. PLoS One 2012; 7(3): e32746.
[http://dx.doi.org/10.1371/journal.pone.0032746] [PMID: 22412919]
[http://dx.doi.org/10.1371/journal.pone.0032746] [PMID: 22412919]
[36]
Thibodeau JF, Holterman CE, Burger D, Read NC, Reudelhuber TL, Kennedy CRJ. A novel mouse model of advanced diabetic kidney disease. PLoS One 2014; 9(12): e113459.
[http://dx.doi.org/10.1371/journal.pone.0113459] [PMID: 25514595]
[http://dx.doi.org/10.1371/journal.pone.0113459] [PMID: 25514595]
[37]
Wei P, Lane PH, Lane JT, Padanilam BJ, Sansom SC. Glomerular structural and functional changes in a high-fat diet mouse model of early-stage Type 2 diabetes. Diabetologia 2004; 47(9): 1541-9.
[http://dx.doi.org/10.1007/s00125-004-1489-1] [PMID: 15338127]
[http://dx.doi.org/10.1007/s00125-004-1489-1] [PMID: 15338127]
[38]
Xu H, Ma Z, Lu S, et al. Renal resistive index as a novel indicator for renal complications in high-fat diet-fed mice. Kidney Blood Press Res 2017; 42(6): 1128-40.
[http://dx.doi.org/10.1159/000485781] [PMID: 29224015]
[http://dx.doi.org/10.1159/000485781] [PMID: 29224015]
[39]
Zhu H, Zhang W, Zhao Y, et al. GSK3β-mediated tau hyperphosphorylation triggers diabetic retinal neurodegeneration by disrupting synaptic and mitochondrial functions. Mol Neurodegener 2018; 13(1): 62.
[http://dx.doi.org/10.1186/s13024-018-0295-z] [PMID: 30466464]
[http://dx.doi.org/10.1186/s13024-018-0295-z] [PMID: 30466464]
[40]
Xu G, Kang D, Zhang C, et al. Erythropoietin protects retinal cells in diabetic rats through upregulating znt8 via activating ERK pathway and inhibiting HIF-1α expression. Invest Ophthalmol Vis Sci 2015; 56(13): 8166-78.
[http://dx.doi.org/10.1167/iovs.15-18093] [PMID: 26720469]
[http://dx.doi.org/10.1167/iovs.15-18093] [PMID: 26720469]
[41]
Cunha-Vaz JG. Pathophysiology of diabetic retinopathy. Br J Ophthalmol 1978; 62(6): 351-5.
[http://dx.doi.org/10.1136/bjo.62.6.351] [PMID: 666982]
[http://dx.doi.org/10.1136/bjo.62.6.351] [PMID: 666982]
[42]
Hicks CW, Selvin E. Epidemiology of Peripheral Neuropathy and Lower Extremity Disease in Diabetes. Curr Diab Rep 2019; 19(10): 86.
[http://dx.doi.org/10.1007/s11892-019-1212-8] [PMID: 31456118]
[http://dx.doi.org/10.1007/s11892-019-1212-8] [PMID: 31456118]
[43]
Dyck PJ, Albers JW, Andersen H, et al. Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev 2011; 27(7): 620-8.
[http://dx.doi.org/10.1002/dmrr.1226] [PMID: 21695763]
[http://dx.doi.org/10.1002/dmrr.1226] [PMID: 21695763]
[44]
O’Brien PD, Sakowski SA, Feldman EL. Mouse models of diabetic neuropathy. ILAR J 2014; 54(3): 259-72.
[http://dx.doi.org/10.1093/ilar/ilt052] [PMID: 24615439]
[http://dx.doi.org/10.1093/ilar/ilt052] [PMID: 24615439]
[45]
Feldman E, Sullivan K, Lentz S, Roberts J Jr. Criteria for creating and assessing mouse models of diabetic neuropathy. Curr Drug Targets 2008; 9(1): 3-13.
[http://dx.doi.org/10.2174/138945008783431763] [PMID: 18220709]
[http://dx.doi.org/10.2174/138945008783431763] [PMID: 18220709]
[46]
Chung SSM, Ho ECM, Lam KSL, Chung SK. Contribution of polyol pathway to diabetes-induced oxidative stress. J Am Soc Nephrol 2003; 14(8) (Suppl. 3): S233-6.
[http://dx.doi.org/10.1097/01.ASN.0000077408.15865.06] [PMID: 12874437]
[http://dx.doi.org/10.1097/01.ASN.0000077408.15865.06] [PMID: 12874437]
[47]
Kennedy WR, Quick DC, Miyoshi T, Gerritsen GC. Peripheral neurology of the diabetic Chinese hamster. Diabetologia 1982; 23(5): 445-51.
[http://dx.doi.org/10.1007/BF00260960] [PMID: 7173521]
[http://dx.doi.org/10.1007/BF00260960] [PMID: 7173521]
[48]
Zhu H, Yu L, He Y, Wang B. Nonhuman primate models of type 1 diabetes mellitus for islet transplantation. J Diabetes Res 2014; 2014: 1-9.
[http://dx.doi.org/10.1155/2014/785948] [PMID: 25389531]
[http://dx.doi.org/10.1155/2014/785948] [PMID: 25389531]
[49]
Glassock RJ, Warnock DG, Delanaye P. The global burden of chronic kidney disease: estimates, variability and pitfalls. Nat Rev Nephrol 2017; 13(2): 104-14.
[http://dx.doi.org/10.1038/nrneph.2016.163] [PMID: 27941934]
[http://dx.doi.org/10.1038/nrneph.2016.163] [PMID: 27941934]
[50]
Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. Lancet 2013; 382(9888): 260-72.
[http://dx.doi.org/10.1016/S0140-6736(13)60687-X] [PMID: 23727169]
[http://dx.doi.org/10.1016/S0140-6736(13)60687-X] [PMID: 23727169]
[51]
Arora MK, Singh UK. Molecular mechanisms in the pathogenesis of diabetic nephropathy: An update. Vascul Pharmacol 2013; 58(4): 259-71.
[http://dx.doi.org/10.1016/j.vph.2013.01.001] [PMID: 23313806]
[http://dx.doi.org/10.1016/j.vph.2013.01.001] [PMID: 23313806]
[52]
Nazar CM. Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease. J Nephropharmacol 2014; 3(1): 15-20.
[PMID: 28197454]
[PMID: 28197454]
[53]
Zheng S, Noonan WT, Metreveli NS, et al. Development of late-stage diabetic nephropathy in OVE26 diabetic mice. Diabetes 2004; 53(12): 3248-57.
[http://dx.doi.org/10.2337/diabetes.53.12.3248] [PMID: 15561957]
[http://dx.doi.org/10.2337/diabetes.53.12.3248] [PMID: 15561957]
[54]
Herring IP, Panciera DL, Werre SR. Longitudinal prevalence of hypertension, proteinuria, and retinopathy in dogs with spontaneous diabetes mellitus. J Vet Intern Med 2014; 28(2): 488-95.
[http://dx.doi.org/10.1111/jvim.12286] [PMID: 24417733]
[http://dx.doi.org/10.1111/jvim.12286] [PMID: 24417733]
[55]
Heckler K, Kroll J. Zebrafish as a Model for the Study of Microvascular Complications of Diabetes and Their Mechanisms. Int J Mol Sci 2017; 18(9): 2002.
[http://dx.doi.org/10.3390/ijms18092002] [PMID: 28925940]
[http://dx.doi.org/10.3390/ijms18092002] [PMID: 28925940]
[56]
Na J, Sweetwyne MT, Park ASD, Susztak K, Cagan RL. Diet-induced podocyte dysfunction in drosophila and mammals. Cell Rep 2015; 12(4): 636-47.
[http://dx.doi.org/10.1016/j.celrep.2015.06.056] [PMID: 26190114]
[http://dx.doi.org/10.1016/j.celrep.2015.06.056] [PMID: 26190114]
[57]
Gurley SB, Clare SE, Snow KP, Hu A, Meyer TW, Coffman TM. Impact of genetic background on nephropathy in diabetic mice. Am J Physiol Renal Physiol 2006; 290(1): F214-22.
[http://dx.doi.org/10.1152/ajprenal.00204.2005] [PMID: 16118394]
[http://dx.doi.org/10.1152/ajprenal.00204.2005] [PMID: 16118394]
