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Rodent Models of Diabetes

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Principles of Diabetes Mellitus

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Abstract

Currently, diabetes affects approximately 29 million Americans (http://www.cdc.gov/diabetes/basics/index.html) and 380 million people worldwide (IDF Diabetes Atlas: www.idf.org/diabetesatlas). The significant progress in understanding diabetes and its clinical management is, in part, the result of research using rodent models of diabetes. Parallels between humans and rodents make these diabetes models practical tools for studying the characteristic features of diabetes and preclinical evaluation of potential treatments. This chapter describes major rodent models of type 1 and type 2 diabetes and highlights some of the latest developments based on selective genetic modifications in rodents. While these models allow providing further mechanistic insight into disease pathogenesis and testing novel diagnostic and treatment approaches, the strengths and limitations of each model should be considered when designing experiments and interpreting results.

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References

  1. Roth J, Qureshi S, Whitford I, Vranic M, Kahn CR, Fantus IG, et al. Insulin's discovery: new insights on its ninetieth birthday. Diabetes Metab Res Rev. 2012;28:293–304.

    Article  CAS  PubMed  Google Scholar 

  2. Van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev. 2011;91:79–118.

    Article  PubMed  CAS  Google Scholar 

  3. Bakay M, Pandey R, Hakonarson H. Genes involved in type 1 diabetes: an update. Genes. 2013;4:499–521.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Mehers KL, Gillespie KM. The genetic basis for type 1 diabetes. Br Med Bull. 2008;88:115–29.

    Article  CAS  PubMed  Google Scholar 

  5. Rakieten N, Rakieten ML, Nadkarni MV. Studies on the diabetogenic action of streptozotocin (NSC-37917). Cancer Chemother Rep. 1963;29:91–8.

    Google Scholar 

  6. Mansford KR, Opie L. Comparison of metabolic abnormalities in diabetes mellitus induced by streptozotocin or by alloxan. Lancet. 1968;1:670–1.

    Article  CAS  PubMed  Google Scholar 

  7. Wang Z, Gleichmann H. GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice. Diabetes. 1998;47:50–6.

    Article  CAS  PubMed  Google Scholar 

  8. Fozzard HA, Beeler Jr GW. The voltage clamp and cardiac electrophysiology. Circ Res. 1975;37:403–13.

    Article  CAS  PubMed  Google Scholar 

  9. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51:216–26.

    Article  CAS  PubMed  Google Scholar 

  10. Like AA, Rossini AA. Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science. 1976;193:415–7.

    Article  CAS  PubMed  Google Scholar 

  11. Yamamoto H, Uchigata Y, Okamoto H. Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets. Nature. 1981;294:284–6.

    Article  CAS  PubMed  Google Scholar 

  12. Deeds MC, Anderson JM, Armstrong AS, Gastineau DA, Hiddinga HJ, Jahangir A, et al. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab Anim. 2011;45:131–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Reddy S, Wu D, Elliott RB. Low dose streptozotocin causes diabetes in severe combined immunodeficient (SCID) mice without immune cell infiltration of the pancreatic islets. Autoimmunity. 1995;20:83–92.

    Article  CAS  PubMed  Google Scholar 

  14. Dekel Y, Glucksam Y, Elron-Gross I, Margalit R. Insights into modeling streptozotocin-induced diabetes in ICR mice. Lab Anim. 2009;38:55–60.

    Article  Google Scholar 

  15. Lukic ML, Stosic-Grujicic S, Shahin A. Effector mechanisms in low-dose streptozotocin-induced diabetes. Dev Immunol. 1998;6:119–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wei M, Ong L, Smith MT, Ross FB, Schmid K, Hoey AJ, et al. The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes. Heart Lung Circ. 2003;12:44–50.

    Article  PubMed  Google Scholar 

  17. Szkudelski T. Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med. 2012;237:481–90.

    Article  CAS  Google Scholar 

  18. Dunn JS, Duffy E, Gilmour MK, Kirkpatrick J, McLetchie NG. Further observations on the effects of alloxan on the pancreatic islets. J Physiol. 1944;103:233–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mrozikiewicz A, Kielczewska-Mrozikiewicz D, Lowicki Z, Chmara E, Korzeniowska K, Mrozikiewicz PM. Blood levels of alloxan in children with insulin-dependent diabetes mellitus. Acta Diabetol. 1994;31:236–7.

    Article  CAS  PubMed  Google Scholar 

  20. Hoftiezer V, Carpenter AM. Comparison of streptozotocin and alloxan-induced diabetes in the rat, including volumetric quantitation of the pancreatic islets. Diabetologia. 1973;9:178–84.

    Article  CAS  PubMed  Google Scholar 

  21. 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;54:252–7.

    CAS  PubMed  Google Scholar 

  22. Coppieters KT, Boettler T, von Herrath M. Virus infections in type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2:a007682.

    Article  PubMed  PubMed Central  Google Scholar 

  23. von Herrath M, Filippi C, Coppieters K. How viral infections enhance or prevent type 1 diabetes-from mouse to man. J Med Virol. 2011;83:1672.

    Article  Google Scholar 

  24. Schneider DA, von Herrath MG. Potential viral pathogenic mechanism in human type 1 diabetes. Diabetologia. 2014;57:2009–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lonnrot M, Korpela K, Knip M, Ilonen J, Simell O, Korhonen S, et al. Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study. Diabetes. 2000;49:1314–8.

    Article  CAS  PubMed  Google Scholar 

  26. Dotta F, Censini S, van Halteren AG, Marselli L, Masini M, Dionisi S, et al. Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci U S A. 2007;104:5115–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yoon JW, Onodera T, Notkins AL. Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4. J Exp Med. 1978;148:1068–80.

    Article  CAS  PubMed  Google Scholar 

  28. 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;300:1173–9.

    Article  CAS  PubMed  Google Scholar 

  29. Clements GB, Galbraith DN, Taylor KW. Coxsackie B virus infection and onset of childhood diabetes. Lancet. 1995;346:221–3.

    Article  CAS  PubMed  Google Scholar 

  30. Andreoletti L, Hober D, Hober-Vandenberghe C, Belaich S, Vantyghem MC, Lefebvre J, et al. Detection of coxsackie B virus RNA sequences in whole blood samples from adult patients at the onset of type I diabetes mellitus. J Med Virol. 1997;52:121–7.

    Article  CAS  PubMed  Google Scholar 

  31. Serreze DV, Ottendorfer EW, Ellis TM, Gauntt CJ, Atkinson MA. Acceleration of type 1 diabetes by a coxsackievirus infection requires a preexisting critical mass of autoreactive T-cells in pancreatic islets. Diabetes. 2000;49:708–11.

    Article  CAS  PubMed  Google Scholar 

  32. Tracy S, Drescher KM, Chapman NM, Kim KS, Carson SD, Pirruccello S, et al. Toward testing the hypothesis that group B coxsackieviruses (CVB) trigger insulin-dependent diabetes: inoculating nonobese diabetic mice with CVB markedly lowers diabetes incidence. J Virol. 2002;76:12097–111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bason C, Lorini R, Lunardi C, Dolcino M, Giannattasio A, d’Annunzio G, et al. In type 1 diabetes a subset of anti-coxsackievirus B4 antibodies recognize autoantigens and induce apoptosis of pancreatic beta cells. PLoS One. 2013;8:e57729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Craighead JE, McLane MF. Diabetes mellitus: induction in mice by encephalomyocarditis virus. Science. 1968;162:913–4.

    Article  CAS  PubMed  Google Scholar 

  35. Hirasawa K, Jun HS, Maeda K, Kawaguchi Y, Itagaki S, Mikami T, et al. Possible role of macrophage-derived soluble mediators in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. J Virol. 1997;71:4024–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Kang Y, Yoon JW. A genetically determined host factor controlling susceptibility to encephalomyocarditis virus-induced diabetes in mice. J Gen Virol. 1993;74(Pt 6):1207–13.

    Article  CAS  PubMed  Google Scholar 

  37. Baek HS, Yoon JW. Direct involvement of macrophages in destruction of beta-cells leading to development of diabetes in virus-infected mice. Diabetes. 1991;40:1586–97.

    Article  CAS  PubMed  Google Scholar 

  38. Shimada A, Maruyama T. Encephalomyocarditis-virus-induced diabetes model resembles “fulminant” type 1 diabetes in humans. Diabetologia. 2004;47:1854–5.

    Article  CAS  PubMed  Google Scholar 

  39. Ellerman KE, Richards CA, Guberski DL, Shek WR, Like AA. Kilham rat triggers T-cell-dependent autoimmune diabetes in multiple strains of rat. Diabetes. 1996;45:557–62.

    Article  CAS  PubMed  Google Scholar 

  40. 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;254:1010–3.

    Article  CAS  PubMed  Google Scholar 

  41. Zipris D, Lien E, Xie JX, Greiner DL, Mordes JP, Rossini AA. TLR activation synergizes with Kilham rat virus infection to induce diabetes in BBDR rats. J Immunol. 2005;174:131–42.

    Article  CAS  PubMed  Google Scholar 

  42. Alkanani AK, Hara N, Gianani R, Zipris D. Kilham Rat Virus-induced type 1 diabetes involves beta cell infection and intra-islet JAK-STAT activation prior to insulitis. Virology. 2014;468–470:19–27. doi:10.1016/j.virol.2014.07.041. Epub 16 Aug 2014.

    Article  PubMed  CAS  Google Scholar 

  43. Tirabassi RS, Guberski DL, Blankenhorn EP, Leif JH, Woda BA, Liu Z, et al. Infection with viruses from several families triggers autoimmune diabetes in LEW*1WR1 rats: prevention of diabetes by maternal immunization. Diabetes. 2010;59:110–8.

    Article  CAS  PubMed  Google Scholar 

  44. von Herrath MG, Homann D, Gairin JE, Oldstone MB. Pathogenesis and treatment of virus-induced autoimmune diabetes: novel insights gained from the RIP-LCMV transgenic mouse model. Biochem Soc Trans. 1997;25:630–5.

    Article  Google Scholar 

  45. Oldstone MB, Nerenberg M, Southern P, Price J, Lewicki H. Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell. 1991;65:319–31.

    Article  CAS  PubMed  Google Scholar 

  46. Ohashi PS, Oehen S, Buerki K, Pircher H, Ohashi CT, Odermatt B, et al. Ablation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice. Cell. 1991;65:305–17.

    Article  CAS  PubMed  Google Scholar 

  47. Banting FG. An address on diabetes and insulin: being the nobel lecture delivered at Stockholm on september 15th, 1925. Can Med Assoc J. 1926;16:221–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Gordon CS, Serino AS, Krause MP, Campbell JE, Cafarelli E, Adegoke OA, et al. Impaired growth and force production in skeletal muscles of young partially pancreatectomized rats: a model of adolescent type 1 diabetic myopathy? PLoS One. 2010;5:e14032.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, et al. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature. 2008;455:1109–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. King AJ. The use of animal models in diabetes research. Br J Pharmacol. 2012;166:877–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y. Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu. 1980;29:1–13.

    CAS  PubMed  Google Scholar 

  52. Thayer TC, Wilson SB, Mathews CE. Use of nonobese diabetic mice to understand human type 1 diabetes. Endocrinol Metab Clin North Am. 2010;39:541–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wicker LS, Todd JA, Peterson LB. Genetic control of autoimmune diabetes in the NOD mouse. Annu Rev Immunol. 1995;13:179–200.

    Article  CAS  PubMed  Google Scholar 

  54. Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003;423:506–11.

    Article  CAS  PubMed  Google Scholar 

  55. Kristiansen OP, Larsen ZM, Pociot F. CTLA-4 in autoimmune diseases – a general susceptibility gene to autoimmunity? Genes Immun. 2000;1:170–84.

    Article  CAS  PubMed  Google Scholar 

  56. Lundholm M, Motta V, Lofgren-Burstrom A, Duarte N, Bergman ML, Mayans S, et al. Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of Idd3/IL-2 and a novel locus (Ctex) telomeric on chromosome 1. Diabetes. 2006;55:538–44.

    Article  CAS  PubMed  Google Scholar 

  57. King C, Sarvetnick N. The incidence of type-1 diabetes in NOD mice is modulated by restricted flora not germ-free conditions. PLoS One. 2011;6:e17049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Driver JP, Serreze DV, Chen YG. Mouse models for the study of autoimmune type 1 diabetes: a NOD to similarities and differences to human disease. Semin Immunopathol. 2011;33:67–87.

    Article  CAS  PubMed  Google Scholar 

  59. Guberski DL. Diabetes-prone and diabetes-resistant BB rats: animal models of spontaneous and virally induced diabetes mellitus, lymphocytic thyroiditis, and collagen-induced arthritis. ILAR J. 1993;35:29–37.

    Article  Google Scholar 

  60. Poussier P, Ning T, Murphy T, Dabrowski D, Ramanathan S. Impaired post-thymic development of regulatory CD4 + 25+ T cells contributes to diabetes pathogenesis in BB rats. J Immunol. 2005;174:4081–9.

    Article  CAS  PubMed  Google Scholar 

  61. Poussier P, Nakhooda AF, Falk JA, Lee C, Marliss EB. Lymphopenia and abnormal lymphocyte subsets in the “BB” rat: relationship to the diabetic syndrome. Endocrinology. 1982;110:1825–7.

    Article  CAS  PubMed  Google Scholar 

  62. Wallis RH, Wang K, Marandi L, Hsieh E, Ning T, Chao GY, et al. Type 1 diabetes in the BB rat: a polygenic disease. Diabetes. 2009;58:1007–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Komeda K, Noda M, Terao K, Kuzuya N, Kanazawa M, Kanazawa Y. Establishment of two substrains, diabetes-prone and non-diabetic, from Long-Evans Tokushima Lean (LETL) rats. Endocr J. 1998;45:737–44.

    Article  CAS  PubMed  Google Scholar 

  64. 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;31:391–4.

    CAS  PubMed  Google Scholar 

  65. 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;54:2727–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Lenzen S, Tiedge M, Elsner M, Lortz S, Weiss H, Jorns A, et al. The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus. Diabetologia. 2001;44:1189–96.

    Article  CAS  PubMed  Google Scholar 

  67. Jorns A, Gunther 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;54:2041–52.

    Article  PubMed  Google Scholar 

  68. Centers for Disease Control and Prevention (CDC). Awareness of prediabetes – United States, 2005–2010. MMWR Morb Mortal Wkly Rep. 2013;62:209–12.

    Google Scholar 

  69. Dickie MMLP. Plus letter to Roy Robinson 7/7/70. Mouse News Lett. 1957;17:52.

    Google Scholar 

  70. Bahary N, Siegel DA, Walsh J, Zhang Y, Leopold L, Leibel R, et al. Microdissection of proximal mouse chromosome 6: identification of RFLPs tightly linked to the ob mutation. Mamm Genome. 1993;4:511–5.

    Article  CAS  PubMed  Google Scholar 

  71. Friedman JM, Leibel RL, Siegel DS, Walsh J, Bahary N. Molecular mapping of the mouse ob mutation. Genomics. 1991;11:1054–62.

    Article  CAS  PubMed  Google Scholar 

  72. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.

    Article  CAS  PubMed  Google Scholar 

  73. Brennan AM, Mantzoros CS. Drug Insight: the role of leptin in human physiology and pathophysiology – emerging clinical applications. Nat Clin Pract Endocrinol Metab. 2006;2:318–27.

    Article  CAS  PubMed  Google Scholar 

  74. Carlsson B, Lindell K, Gabrielsson B, Karlsson C, Bjarnason R, Westphal O, et al. Obese (ob) gene defects are rare in human obesity. Obes Res. 1997;5:30–5.

    Article  CAS  PubMed  Google Scholar 

  75. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395:763–70.

    Article  CAS  PubMed  Google Scholar 

  76. Hummel KP, Coleman DL, Lane PW. The influence of genetic background on expression of mutations at the diabetes locus in the mouse. I. C57BL-KsJ and C57BL-6J strains. Biochem Genet. 1972;7:1–13.

    Article  CAS  PubMed  Google Scholar 

  77. Lindstrom P. The physiology of obese-hyperglycemic mice [ob/ob mice]. Scientific World Journal. 2007;7:666–85.

    Article  PubMed  CAS  Google Scholar 

  78. Coleman DL, Hummel KP. The influence of genetic background on the expression of the obese (Ob) gene in the mouse. Diabetologia. 1973;9:287–93.

    Article  CAS  PubMed  Google Scholar 

  79. Chua Jr S, Liu SM, Li Q, Yang L, Thassanapaff VT, Fisher P. Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB- Lepr (db)) and obese (DBA- Lep (ob)) mice. Diabetologia. 2002;45:976–90.

    Article  CAS  PubMed  Google Scholar 

  80. Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 1996;12:318–20.

    Article  CAS  PubMed  Google Scholar 

  81. Mounzih K, Lu R, Chehab FF. Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology. 1997;138:1190–3.

    Article  CAS  PubMed  Google Scholar 

  82. Hummel KP, Dickie MM, Coleman DL. Diabetes, a new mutation in the mouse. Science. 1966;153:1127–8.

    Article  CAS  PubMed  Google Scholar 

  83. Zucker L, Zucker T. Fatty, a new mutation in the rat. J Hered. 1961;52:275–8.

    Google Scholar 

  84. Peterson R, Shaw W, Neel MA, Little LA, Eichberg J. Zucker diabetic fatty rat as a model for non-insulin dependent diabetes mellitus. ILAR News. 1990;32:16–9.

    Article  Google Scholar 

  85. 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;13:18–9.

    Article  CAS  PubMed  Google Scholar 

  86. Durham HA, Truett GE. Development of insulin resistance and hyperphagia in Zucker fatty rats. Am J Physiol Regul Integr Comp Physiol. 2006;290:R652–8.

    Article  CAS  PubMed  Google Scholar 

  87. Kava R, Greenwood M, Johnson P. Zucker (fa/fa) rat. ILAR J. 1990;32:4–8.

    Article  Google Scholar 

  88. Baynes J, Murray DB. Cardiac and renal function are progressively impaired with aging in Zucker diabetic fatty type II diabetic rats. Oxid Med Cell Longev. 2009;2:328–34.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Kim J, Sohn E, Kim CS, Kim JS. Renal podocyte apoptosis in Zucker diabetic fatty rats: involvement of methylglyoxal-induced oxidative DNA damage. J Comp Pathol. 2011;144:41–7.

    Article  CAS  PubMed  Google Scholar 

  90. Taketomi S, Tsuda M, Matsuo T, Iwatsuka H, Suzuoki Z. Alterations of hepatic enzyme activities in KK and yellow KK mice with various diabetic states. Horm Metab Res. 1973;5:333–9.

    Article  CAS  PubMed  Google Scholar 

  91. Ikeda H. KK mouse. Diabetes Res Clin Pract. 1994;24(Suppl):S313–6.

    Article  PubMed  Google Scholar 

  92. Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Res. 2007;125:451–72.

    CAS  PubMed  Google Scholar 

  93. Miltenberger RJ, Mynatt RL, Wilkinson JE, Woychik RP. The role of the agouti gene in the yellow obese syndrome. J Nutr. 1997;127:1902S–7.

    CAS  PubMed  Google Scholar 

  94. Roberts DW, Wolff GL, Campbell WL. Differential effects of the mottled yellow and pseudoagouti phenotypes on immunocompetence in Avy/a mice. Proc Natl Acad Sci U S A. 1984;81:2152–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Frigeri LG, Teguh C, Ling N, Wolff GL, Lewis UJ. Increased sensitivity of adipose tissue to insulin after in vivo treatment of yellow Avy/A obese mice with amino-terminal peptides of human growth hormone. Endocrinology. 1988;122:2940–5.

    Article  CAS  PubMed  Google Scholar 

  96. Yen TT, Greenberg MM, Yu PL, Pearson DV. An analysis of the relationships among obesity, plasma insulin and hepatic lipogenic enzymes in “viable yellow obese” mice (Avy/a). Horm Metab Res. 1976;8:159–66.

    Article  CAS  PubMed  Google Scholar 

  97. Yen TT, McKee MM, Stamm NB. Thermogenesis and weight control. Int J Obes. 1984;8 Suppl 1:65–78.

    CAS  PubMed  Google Scholar 

  98. Bray GA, York DA. Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol Rev. 1979;59:719–809.

    CAS  PubMed  Google Scholar 

  99. Yen TT, Gill AM, Frigeri LG, Barsh GS, Wolff GL. Obesity, diabetes, and neoplasia in yellow A(vy)/- mice: ectopic expression of the agouti gene. FASEB J. 1994;8:479–88.

    CAS  PubMed  Google Scholar 

  100. Bielschowsky M, Bielschowsky F. A new strain of mice with hereditary obesity. Proc Univ Otago Med Sch. 1953;31:29–31.

    Google Scholar 

  101. Leiter EH, Reifsnyder PC. Differential levels of diabetogenic stress in two new mouse models of obesity and type 2 diabetes. Diabetes. 2004;53 Suppl 1:S4–11.

    Article  CAS  PubMed  Google Scholar 

  102. Bray GA, York DA. Genetically transmitted obesity in rodents. Physiol Rev. 1971;51:598–646.

    CAS  PubMed  Google Scholar 

  103. Ortlepp JR, Kluge R, Giesen K, Plum L, Radke P, Hanrath P, et al. A metabolic syndrome of hypertension, hyperinsulinaemia and hypercholesterolaemia in the New Zealand obese mouse. Eur J Clin Invest. 2000;30:195–202.

    Article  CAS  PubMed  Google Scholar 

  104. Haskell BD, Flurkey K, Duffy TM, Sargent EE, Leiter EH. The diabetes-prone NZO/HlLt strain. I. Immunophenotypic comparison to the related NZB/BlNJ and NZW/LacJ strains. Lab Invest. 2002;82:833–42.

    Article  PubMed  Google Scholar 

  105. Leiter EH, Reifsnyder PC, Flurkey K, Partke HJ, Junger E, Herberg L. NIDDM genes in mice: deleterious synergism by both parental genomes contributes to diabetogenic thresholds. Diabetes. 1998;47:1287–95.

    Article  CAS  PubMed  Google Scholar 

  106. Junger E, Herberg L, Jeruschke K, Leiter EH. The diabetes-prone NZO/Hl strain. II. Pancreatic immunopathology. Lab Invest. 2002;82:843–53.

    Article  PubMed  Google Scholar 

  107. Shibata M, Yasuda B. New experimental congenital diabetic mice (N.S.Y. mice). Tohoku J Exp Med. 1980;130:139–42.

    Article  CAS  PubMed  Google Scholar 

  108. Ueda H, Ikegami H, Yamato E, Fu J, Fukuda M, Shen G, et al. The NSY mouse: a new animal model of spontaneous NIDDM with moderate obesity. Diabetologia. 1995;38:503–8.

    Article  CAS  PubMed  Google Scholar 

  109. Ikegami H, Fujisawa T, Ogihara T. Mouse models of type 1 and type 2 diabetes derived from the same closed colony: genetic susceptibility shared between two types of diabetes. ILAR J. 2004;45:268–77.

    Article  CAS  PubMed  Google Scholar 

  110. Kim JH, Sen S, Avery CS, Simpson E, Chandler P, Nishina PM, et al. Genetic analysis of a new mouse model for non-insulin-dependent diabetes. Genomics. 2001;74:273–86.

    Article  CAS  PubMed  Google Scholar 

  111. Kim JH, Stewart TP, Soltani-Bejnood M, Wang L, Fortuna JM, Mostafa OA, et al. Phenotypic characterization of polygenic type 2 diabetes in TALLYHO/JngJ mice. J Endocrinol. 2006;191:437–46.

    Article  CAS  PubMed  Google Scholar 

  112. Nakamura N. Reduced aldehyde dehydrogenase activity and arginine vasopressin receptor 2 expression in the kidneys of male TALLYHO/JngJ mice of prediabetic age. Endocrine. 2011;40:379–85.

    Article  CAS  PubMed  Google Scholar 

  113. Kim JH, Saxton AM. The TALLYHO mouse as a model of human type 2 diabetes. Methods Mol Biol. 2012;933:75–87. doi:10.1007/978-1-62703-068-7_6.:75-87.

    CAS  PubMed  Google Scholar 

  114. Cho YR, Kim HJ, Park SY, Ko HJ, Hong EG, Higashimori T, et al. Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetes. Am J Physiol Endocrinol Metab. 2007;293:E327–36.

    Article  CAS  PubMed  Google Scholar 

  115. Blaber SI, Diaz J, Blaber M. Accelerated healing in NONcNZO10/LtJ type 2 diabetic mice by FGF-1. Wound Repair Regen. 2015;23:538–49.

    Article  PubMed  Google Scholar 

  116. Zhang S, Wang S, Puhl MD, Jiang X, Hyrc KL, Laciny E, et al. Global biochemical profiling identifies beta-hydroxypyruvate as a potential mediator of type 2 diabetes in mice and humans. Diabetes. 2015;64:1383–94.

    Article  CAS  PubMed  Google Scholar 

  117. Kawano K, Hirashima T, Mori S, Natori T. OLETF (Otsuka Long-Evans Tokushima Fatty) rat: a new NIDDM rat strain. Diabetes Res Clin Pract. 1994;24(Suppl):S317–20.

    Article  PubMed  Google Scholar 

  118. Moran TH. Unraveling the obesity of OLETF rats. Physiol Behav. 2008;94:71–8.

    Article  CAS  PubMed  Google Scholar 

  119. Nara Y, Gao M, Ikeda K, Sato T, Sawamura M, Kawano K, et al. Genetic analysis of non-insulin-dependent diabetes mellitus in the Otsuka Long-Evans Tokushima Fatty rat. Biochem Biophys Res Commun. 1997;241:200–4.

    Article  CAS  PubMed  Google Scholar 

  120. Yamada T, Kose H, Ohta T, Matsumoto K. Genetic dissection of complex genetic factor involved in NIDDM of OLETF rat. Exp Diabetes Res. 2012;2012:582546. doi:10.1155/2012/582546. Epub 15 Oct 2012.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Vaag A, Lund SS. Non-obese patients with type 2 diabetes and prediabetic subjects: distinct phenotypes requiring special diabetes treatment and (or) prevention? Appl Physiol Nutr Metab. 2007;32:912–20.

    Article  PubMed  Google Scholar 

  122. Picarel-Blanchot F, Berthelier C, Bailbe D, Portha B. Impaired insulin secretion and excessive hepatic glucose production are both early events in the diabetic GK rat. Am J Physiol. 1996;271:E755–62.

    CAS  PubMed  Google Scholar 

  123. Movassat J, Saulnier C, Serradas P, Portha B. Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat. Diabetologia. 1997;40:916–25.

    Article  CAS  PubMed  Google Scholar 

  124. 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. doi:10.1007/978-1-62703-068-7_9.:125-59.

    CAS  PubMed  Google Scholar 

  125. Shinohara M, Masuyama T, Shoda T, Takahashi T, Katsuda Y, Komeda K, et al. A new spontaneously diabetic non-obese Torii rat strain with severe ocular complications. Int J Exp Diabetes Res. 2000;1:89–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Sasase T, Ohta T, Ogawa N, Miyajima K, Ito M, Yamamoto H, et al. Preventive effects of glycaemic control on ocular complications of Spontaneously Diabetic Torii rat. Diabetes Obes Metab. 2006;8:501–7.

    Article  CAS  PubMed  Google Scholar 

  127. Masuyama T, Fuse M, Yokoi N, Shinohara M, Tsujii H, Kanazawa M, et al. Genetic analysis for diabetes in a new rat model of nonobese type 2 diabetes, Spontaneously Diabetic Torii rat. Biochem Biophys Res Commun. 2003;304:196–206.

    Article  CAS  PubMed  Google Scholar 

  128. Matsui K, Ohta T, Oda T, Sasase T, Ueda N, Miyajima K, et al. Diabetes-associated complications in Spontaneously Diabetic Torii fatty rats. Exp Anim. 2008;57:111–21.

    Article  CAS  PubMed  Google Scholar 

  129. Katsuda Y, Sasase T, Tadaki H, Mera Y, Motohashi Y, Kemmochi Y, et al. Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin. Exp Anim. 2015;64:161–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Islam MS. Animal models of diabetic neuropathy: progress since 1960s. J Diabetes Res. 2013;2013 149452. doi:10.1155/2013/149452. Epub 29 July 2013.

    PubMed  PubMed Central  Google Scholar 

  131. Fujii H, Kono K, Nakai K, Goto S, Komaba H, Hamada Y, et al. Oxidative and nitrosative stress and progression of diabetic nephropathy in type 2 diabetes. Am J Nephrol. 2010;31:342–52.

    Article  CAS  PubMed  Google Scholar 

  132. Barber AJ, Antonetti DA, Kern TS, Reiter CE, Soans RS, Krady JK, et al. The Ins2Akita mouse as a model of early retinal complications in diabetes. Invest Ophthalmol Vis Sci. 2005;46:2210–8.

    Article  PubMed  Google Scholar 

  133. Mathews CE, Langley SH, Leiter EH. New mouse model to study islet transplantation in insulin-dependent diabetes mellitus. Transplantation. 2002;73:1333–6.

    Article  CAS  PubMed  Google Scholar 

  134. Nemery B, Vanlommel S, Verbeken EK, Lauweryns JM, Demedts M. Lung injury induced by paraquat, hyperoxia and cobalt chloride: effects of ambroxol. Pulm Pharmacol. 1992;5:53–60.

    Article  CAS  PubMed  Google Scholar 

  135. Yoshinaga T, Nakatome K, Nozaki J, Naitoh M, Hoseki J, Kubota H, et al. Proinsulin lacking the A7-B7 disulfide bond, Ins2Akita, tends to aggregate due to the exposed hydrophobic surface. Biol Chem. 2005;386:1077–85.

    Article  CAS  PubMed  Google Scholar 

  136. Yoshioka M, Kayo T, Ikeda T, Koizumi A. A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes. 1997;46:887–94.

    Article  CAS  PubMed  Google Scholar 

  137. Hong EG, Jung DY, Ko HJ, Zhang Z, Ma Z, Jun JY, et al. Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling. Am J Physiol Endocrinol Metab. 2007;293:E1687–96.

    Article  CAS  PubMed  Google Scholar 

  138. Sato A, Kawano H, Notsu T, Ohta M, Nakakuki M, Mizuguchi K, et al. Antiobesity effect of eicosapentaenoic acid in high-fat/high-sucrose diet-induced obesity: importance of hepatic lipogenesis. Diabetes. 2010;59:2495–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Satapathy SK, Ochani M, Dancho M, Hudson LK, Rosas-Ballina M, Valdes-Ferrer SI, et al. Galantamine alleviates inflammation and other obesity-associated complications in high-fat diet-fed mice. Mol Med. 2011;17:599–606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Speakman J, Hambly C, Mitchell S, Krol E. Animal models of obesity. Obes Rev. 2007;8 Suppl 1:55–61.

    Article  PubMed  Google Scholar 

  141. Inui A. Obesity – a chronic health problem in cloned mice? Trends Pharmacol Sci. 2003;24:77–80.

    Article  CAS  PubMed  Google Scholar 

  142. Diaz J, Warren L, Helfner L, Xue X, Chatterjee PK, Gupta M, et al. Obesity shifts house dust mite-induced airway cellular infiltration from eosinophils to macrophages: effects of glucocorticoid treatment. Immunol Res. 2015;63:197–208.

    Article  CAS  PubMed  Google Scholar 

  143. Rossmeisl M, Rim JS, Koza RA, Kozak LP. Variation in type 2 diabetes – related traits in mouse strains susceptible to diet-induced obesity. Diabetes. 2003;52:1958–66.

    Article  CAS  PubMed  Google Scholar 

  144. Wang CY, Liao JK. A mouse model of diet-induced obesity and insulin resistance. Methods Mol Biol. 2012;821:421–33. doi:10.1007/978-1-61779-430-8_27.:421-33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Collins S, Martin TL, Surwit RS, Robidoux J. Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics. Physiol Behav. 2004;81:243–8.

    Article  CAS  PubMed  Google Scholar 

  146. Begin-Heick N. Of mice and women: the beta 3-adrenergic receptor leptin and obesity. Biochem Cell Biol. 1996;74:615–22.

    Article  CAS  PubMed  Google Scholar 

  147. Pettersson US, Walden TB, Carlsson PO, Jansson L, Phillipson M. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS One. 2012;7:e46057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Shi H, Clegg DJ. Sex differences in the regulation of body weight. Physiol Behav. 2009;97:199–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Saito K, Cao X, He Y, Xu Y. Progress in the molecular understanding of central regulation of body weight by estrogens. Obesity. 2015;23:919–26.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Rachon D, Teede H. Ovarian function and obesity – interrelationship, impact on women’s reproductive lifespan and treatment options. Mol Cell Endocrinol. 2010;316:172–9.

    Article  CAS  PubMed  Google Scholar 

  151. Dahlman I, Vaxillaire M, Nilsson M, Lecoeur C, Gu HF, Cavalcanti-Proenca C, et al. Estrogen receptor alpha gene variants associate with type 2 diabetes and fasting plasma glucose. Pharmacogenet Genomics. 2008;18:967–75.

    Article  CAS  PubMed  Google Scholar 

  152. Gonet AE, Stauffacher W, Pictet R, Renold AE. Obesity and diabetes mellitus with striking congenital hyperplasia of the islets of langerhans in spiny mice (Acomys cahirinus): I. Histological findings and preliminary metabolic observations. Diabetologia. 1966;1:162–71.

    Article  CAS  PubMed  Google Scholar 

  153. 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;47:212–24.

    Article  CAS  PubMed  Google Scholar 

  154. Ziv E, Kalman R, Hershkop K, Barash V, Shafrir E, Bar-On H. Insulin resistance in the NIDDM model Psammomys obesus in the normoglycaemic, normoinsulinaemic state. Diabetologia. 1996;39:1269–75.

    Article  CAS  PubMed  Google Scholar 

  155. Barnett M, Collier GR, Collier FM, Zimmet P, O’Dea K. A cross-sectional and short-term longitudinal characterisation of NIDDM in Psammomys obesus. Diabetologia. 1994;37:671–6.

    Article  CAS  PubMed  Google Scholar 

  156. Walder KR, Fahey RP, Morton GJ, Zimmet PZ, Collier GR. Characterization of obesity phenotypes in Psammomys obesus (Israeli sand rats). Int J Exp Diabetes Res. 2000;1:177–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Kanety H, Moshe S, Shafrir E, Lunenfeld B, Karasik A. Hyperinsulinemia induces a reversible impairment in insulin receptor function leading to diabetes in the sand rat model of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A. 1994;91:1853–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Shafrir E, Ziv E. Cellular mechanism of nutritionally induced insulin resistance: the desert rodent Psammomys obesus and other animals in which insulin resistance leads to detrimental outcome. J Basic Clin Physiol Pharmacol. 1998;9:347–85.

    Article  CAS  PubMed  Google Scholar 

  159. Refinetti R. The Nile grass rat as a laboratory animal. Lab Anim. 2004;33:54–7.

    Article  Google Scholar 

  160. Blanchong JA, McElhinny TL, Mahoney MM, Smale L. Nocturnal and diurnal rhythms in the unstriped Nile rat, Arvicanthis niloticus. J Biol Rhythms. 1999;14:364–77.

    Article  CAS  PubMed  Google Scholar 

  161. Noda K, Melhorn MI, Zandi S, Frimmel S, Tayyari F, Hisatomi T, et al. An animal model of spontaneous metabolic syndrome: Nile grass rat. FASEB J. 2010;24:2443–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Noda K, Nakao S, Zandi S, Sun D, Hayes KC, Hafezi-Moghadam A. Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm. FASEB J. 2014;28:2038–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Srinivas NR. Strategies for preclinical pharmacokinetic investigation in streptozotocin-induced diabetes mellitus (DMIS) and alloxan-induced diabetes mellitus (DMIA) rat models: case studies and perspectives. Eur J Drug Metab Pharmacokinet. 2015;40:1–12.

    Article  CAS  PubMed  Google Scholar 

  164. Bonner-Weir S, Trent DF, Honey RN, Weir GC. Responses of neonatal rat islets to streptozotocin: limited B-cell regeneration and hyperglycemia. Diabetes. 1981;30:64–9.

    Article  CAS  PubMed  Google Scholar 

  165. Blondel O, Bailbe D, Portha B. Relation of insulin deficiency to impaired insulin action in NIDDM adult rats given streptozocin as neonates. Diabetes. 1989;38:610–7.

    Article  CAS  PubMed  Google Scholar 

  166. 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;81:1407–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Bonner-Weir S, Trent DF, Weir GC. Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release. J Clin Invest. 1983;71:1544–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Wang RN, Kloppel G, Bouwens L. Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia. 1995;38:1405–11.

    Article  CAS  PubMed  Google Scholar 

  169. DeSisto CL, Kim SY, Sharma AJ. Prevalence estimates of gestational diabetes mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007–2010. Prev Chronic Dis. 2014;11:E104. doi:10.5888/pcd11.130415.:E104.

    Article  PubMed  PubMed Central  Google Scholar 

  170. Cheung NW, Byth K. Population health significance of gestational diabetes. Diabetes Care. 2003;26:2005–9.

    Article  PubMed  Google Scholar 

  171. Dabelea D, Mayer-Davis EJ, Lamichhane AP, D’Agostino Jr RB, Liese AD, Vehik KS, et al. Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth: the SEARCH Case–control Study. Diabetes Care. 2008;31:1422–6.

    Article  PubMed  PubMed Central  Google Scholar 

  172. Pereira TJ, Moyce BL, Kereliuk SM, Dolinsky VW. Influence of maternal overnutrition and gestational diabetes on the programming of metabolic health outcomes in the offspring: experimental evidence. Biochem Cell Biol. 2014;19:1–14.

    Google Scholar 

  173. Pasek RC, Gannon M. Advancements and challenges in generating accurate animal models of gestational diabetes mellitus. Am J Physiol Endocrinol Metab. 2013;305:E1327–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Liang C, DeCourcy K, Prater MR. High-saturated-fat diet induces gestational diabetes and placental vasculopathy in C57BL/6 mice. Metabolism. 2010;59:943–50.

    Article  CAS  PubMed  Google Scholar 

  175. Holemans K, Caluwaerts S, Poston L, Van Assche FA. Diet-induced obesity in the rat: a model for gestational diabetes mellitus. Am J Obstet Gynecol. 2004;190:858–65.

    Article  PubMed  Google Scholar 

  176. Van Mieghem T, van Bree R, Van Herck E, Deprest J, Verhaeghe J. Insulin-like growth factor-II regulates maternal hemodynamic adaptation to pregnancy in rats. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1615–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  177. Couvreur O, Ferezou J, Gripois D, Serougne C, Crepin D, Aubourg A, et al. Unexpected long-term protection of adult offspring born to high-fat fed dams against obesity induced by a sucrose-rich diet. PLoS One. 2011;6:e18043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Tufino C, Villanueva-Lopez C, Ibarra-Barajas M, Bracho-Valdes I, Bobadilla-Lugo RA. Experimental gestational diabetes mellitus induces blunted vasoconstriction and functional changes in the rat aorta. Biomed Res Int. 2014;2014:329634. doi:10.1155/2014/329634. Epub 28 Dec 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  179. Desai N, Roman A, Rochelson B, Gupta M, Xue X, Chatterjee PK, et al. Maternal metformin treatment decreases fetal inflammation in a rat model of obesity and metabolic syndrome. Am J Obstet Gynecol. 2013;209:136–9.

    Article  PubMed  CAS  Google Scholar 

  180. Accili D, Drago J, Lee EJ, Johnson MD, Cool MH, Salvatore P, et al. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat Genet. 1996;12:106–9.

    Article  CAS  PubMed  Google Scholar 

  181. Tamemoto H, Kadowaki T, Tobe K, Yagi T, Sakura H, Hayakawa T, et al. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature. 1994;372:182–6.

    Article  CAS  PubMed  Google Scholar 

  182. Rees DA, Alcolado JC. Animal models of diabetes mellitus. Diabet Med. 2005;22:359–70.

    Article  CAS  PubMed  Google Scholar 

  183. Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, et al. Disruption of IRS-2 causes type 2 diabetes in mice. Nature. 1998;391:900–4.

    Article  CAS  PubMed  Google Scholar 

  184. Scrocchi LA, Brown TJ, MaClusky N, Brubaker PL, Auerbach AB, Joyner AL, et al. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med. 1996;2:1254–8.

    Article  CAS  PubMed  Google Scholar 

  185. Lee Y, Berglund ED, Wang MY, Fu X, Yu X, Charron MJ, et al. Metabolic manifestations of insulin deficiency do not occur without glucagon action. Proc Natl Acad Sci U S A. 2012;109:14972–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Nagy A. Cre recombinase: the universal reagent for genome tailoring. Genesis. 2000;26:99–109.

    Article  CAS  PubMed  Google Scholar 

  187. Schwartz MW, Guyenet SJ, Cirulli V. The hypothalamus and ss-cell connection in the gene-targeting era. Diabetes. 2010;59:2991–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Magnuson MA, Osipovich AB. Pancreas-specific Cre driver lines and considerations for their prudent use. Cell Metab. 2013;18:9–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Bruning JC, Michael MD, Winnay JN, Hayashi T, Horsch D, Accili D, et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell. 1998;2:559–69.

    Article  CAS  PubMed  Google Scholar 

  190. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell. 1999;96:329–39.

    Article  CAS  PubMed  Google Scholar 

  191. Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289:2122–5.

    Article  CAS  PubMed  Google Scholar 

  192. Guerra C, Navarro P, Valverde AM, Arribas M, Bruning J, Kozak LP, et al. Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance. J Clin Invest. 2001;108:1205–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Nir T, Melton DA, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007;117:2553–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Wang ZV, Mu J, Schraw TD, Gautron L, Elmquist JK, Zhang BB, et al. PANIC-ATTAC: a mouse model for inducible and reversible beta-cell ablation. Diabetes. 2008;57:2137–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Herrera PL. Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development. 2000;127:2317–22.

    CAS  PubMed  Google Scholar 

  196. Collombat P, Xu X, Ravassard P, Sosa-Pineda B, Dussaud S, Billestrup N, et al. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. Cell. 2009;138:449–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Liu Z, Habener JF. Alpha cells beget beta cells. Cell. 2009;138:424–6.

    Article  CAS  PubMed  Google Scholar 

  198. Deisseroth K. Optogenetics. Nat Methods. 2011;8:26–9.

    Article  CAS  PubMed  Google Scholar 

  199. Allen BD, Singer AC, Boyden ES. Principles of designing interpretable optogenetic behavior experiments. Learn Mem. 2015;22:232–8.

    Article  PubMed  PubMed Central  Google Scholar 

  200. Zhao S, Ting JT, Atallah HE, Qiu L, Tan J, Gloss B, et al. Cell type-specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function. Nat Methods. 2011;8:745–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Kushibiki T, Okawa S, Hirasawa T, Ishihara M. Optogenetic control of insulin secretion by pancreatic beta-cells in vitro and in vivo. Gene Ther. 2015;22:553–9.

    Article  CAS  PubMed  Google Scholar 

  202. Ye H, Daoud-El Baba M, Peng RW, Fussenegger M. A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science. 2011;332:1565–8.

    Article  CAS  PubMed  Google Scholar 

  203. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339:819–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol. 2014;32:347–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Pelletier S, Gingras S, Green DR. Mouse genome engineering via CRISPR-Cas9 for study of immune function. Immunity. 2015;42:18–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Bao D, Ma Y, Zhang X, Guan F, Chen W, Gao K, et al. Preliminary characterization of a leptin receptor knockout rat created by CRISPR/Cas9 system. Sci Rep. 2015;5:15942.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  207. Pavlov VA, Tracey KJ. The vagus nerve and the inflammatory reflex – linking immunity and metabolism. Nat Rev Endocrinol. 2012;8:743–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Scherer T, Lindtner C, Zielinski E, O’Hare J, Filatova N, Buettner C. Short term voluntary overfeeding disrupts brain insulin control of adipose tissue lipolysis. J Biol Chem. 2012;287:33061–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Shin AC, Fasshauer M, Filatova N, Grundell LA, Zielinski E, Zhou JY, et al. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. Cell Metab. 2014;20:898–909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to thank Kevin J. Tracey, Christoph Buettner, and Margot Puerta for critically reading the manuscript.

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Authors and Affiliations

  1. Laboratory of Medicinal Biochemistry, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA

    Christine N. Metz

  2. Hofstra Northwell School of Medicine, Hempstead, NY, USA

    Christine N. Metz, LaQueta K. Hudson & Valentin A. Pavlov

  3. Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA

    LaQueta K. Hudson & Valentin A. Pavlov

  4. Department of Molecular Medicine, Hofstra Northwell School of Medicine, New York, NY, USA

    Valentin A. Pavlov

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  1. Christine N. Metz
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  2. LaQueta K. Hudson
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Correspondence to Valentin A. Pavlov .

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  1. Division of Endocrinology, Gerald J. Friedman Diabetes Institute, Lenox Hill Hospital, Hofstra Northwell School of Medicine, Northwell Health, New York, New York, USA

    Leonid Poretsky

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Metz, C.N., Hudson, L.K., Pavlov, V.A. (2017). Rodent Models of Diabetes. In: Poretsky, L. (eds) Principles of Diabetes Mellitus. Springer, Cham. https://doi.org/10.1007/978-3-319-18741-9_11

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