Type 2 Diabetes pp 19-36

Part of the Methods in Molecular Biology book series (MIMB, volume 560) | Cite as

Nutritional Models of Type 2 Diabetes Mellitus

Protocol

Summary

In order to better understand the events which precede and precipitate the onset of type 2 diabetes (T2DM) several nutritional animal models have been developed. These models are generated by manipulating the diet of either the animal itself or its mother during her pregnancy and, in comparison to traditional genetic and knock out models, have the advantage that they more accurately reflect the aetiology of human T2DM. This chapter will discuss some of the most widely used nutritional models of T2DM: Diet-induced obesity (DIO) in adult rodents, and studies of prenatal and postnatal nutrition in offspring of mothers fed a low-protein diet or overnourished during pregnancy. Several common mechanisms have been identified through which these nutritional manipulations can lead to metabolic disease, including pancreatic beta-cell dysfunction, impaired insulin signalling in skeletal muscle and the excess accumulation of visceral adipose tissue and consequent deposition of non-esterified fatty acids in peripheral tissues resulting in peripheral insulin resistance. The following chapter will discuss each of these nutritional models, their application and relationship to human aetiology, and will highlight the important insights these models have provided into the pathogenesis of T2DM.

Key words

Type 2 diabetes Obesity Insulin resistance Animal models Nutrition High-fat diet Programming 

References

  1. 1.
    Buettner, R., Scholmerich, J., and Bollheimer, L. C. (2007). High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity 15, 798–808PubMedCrossRefGoogle Scholar
  2. 2.
    Portha, B., Blondel, O., Serradas, P., McEvoy, R., Giroix, M. H., Kergoat, M., and Bailbe, D. (1989),. The rat models of non-insulin dependent diabetes induced by neonatal streptozotocin. Diabetes Metab 15, 61–75Google Scholar
  3. 3.
    Bray, G. A. (2004). Medical consequences of obesity. J Clin Endocrinol Metab 89, 2583–2589PubMedCrossRefGoogle Scholar
  4. 4.
    Goralski, K. B. and Sinal, C. J. (2007). Type 2 diabetes and cardiovascular disease: getting to the fat of the matter. Can J Physiol Pharmacol 85, 113–132PubMedCrossRefGoogle Scholar
  5. 5.
    Smith, S. R., Lovejoy, J. C., Greenway, F., Ryan, D., deJonge, L., de la Bretonne, J., Volafova, J., and Bray, G. A. (2001). Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism 50, 425–435PubMedCrossRefGoogle Scholar
  6. 6.
    Ravussin, E. and Smith, S. R. (2002). Increased fat uptake, impaired fat oxidation, and failure of fat cell proliferation result in ectopic fat storage, insulin resistance, and type 2 diabetes. Ann N Y Acad Sci 967, 363–378PubMedCrossRefGoogle Scholar
  7. 7.
    Surwit, R. S., Kuhn, C. M., Cochrane, C., McCubbin, J. A., and Feinglos, M. N. (1988). Diet-induced type II diabetes in C57BL/6J mice. Diabetes 37, 1163–1167PubMedCrossRefGoogle Scholar
  8. 8.
    Roberts, C. K., Berger, J. J., and Barnard, R. J. (2002). Long-term effects of diet on leptin, energy intake, and activity in a model of diet-induced obesity. J Appl Physiol 93, 887–893PubMedGoogle Scholar
  9. 9.
    Bayol, S. A., Farrington, S. J., and Stickland, N. C. (2007). A maternal ‘junk food’ diet in pregnancy and lactation promotes an exacerbated taste for ‘junk food’ and a greater propensity for obesity in rat offspring. Br J Nutr 98, 843–851PubMedCrossRefGoogle Scholar
  10. 10.
    Taylor, P. D., McConnell, J., Khan, I. Y., Holemans, K., Lawrence, K. M., Asare-Anane, H., Persaud, S. J., Jones, P. M., Petrie, L., Hanson, M. A., and Poston, L. (2005). Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. Am J Physiol Regul Integr Comp Physiol 288, R134–R139PubMedCrossRefGoogle Scholar
  11. 11.
    Woods, S. C., Seeley, R. J., Rushing, P. A., D’Alessio, D., and Tso, P. (2003). A controlled high-fat diet induces an obese syndrome in rats. J Nutr 133, 1081–1087PubMedGoogle Scholar
  12. 12.
    Qiu, L., List, E. O., and Kopchick, J. J. (2005). Differentially expressed proteins in the pancreas of diet-induced diabetic mice. Mol Cell Proteomics 4, 1311–1318PubMedCrossRefGoogle Scholar
  13. 13.
    Corbett, S. W., Stern, J. S., and Keesey, R. E. (1986), Energy expenditure in rats with diet-induced obesity. Am J Clin Nutr 44, 173–180PubMedGoogle Scholar
  14. 14.
    Yaqoob, P., Sherrington, E. J., Jeffery, N. M., Sanderson, P., Harvey, D. J., Newsholme, E. A., and Calder, P. C. (1995), Comparison of the effects of a range of dietary lipids upon serum and tissue lipid composition in the rat. Int J Biochem Cell Biol 27, 297–310PubMedCrossRefGoogle Scholar
  15. 15.
    Levin, B. E., Hogan, S., and Sullivan, A. C. (1989), Initiation and perpetuation of obesity and obesity resistance in rats. Am J Physiol Regul Integr Comp Physiol 256, R766–R771Google Scholar
  16. 16.
    Clegg, D. J., Benoit, S. C., Reed, J. A., Woods, S. C., Dunn-Meynell, A., and Levin, B. E. (2005). Reduced anorexic effects of insulin in obesity-prone rats fed a moderate-fat diet. Am J Physiol Regul Integr Comp Physiol 288, R981–R986PubMedCrossRefGoogle Scholar
  17. 17.
    Levin, B. E., Dunn-Meynell, A. A., Balkan, B., and Keesey, R. E. (1997). Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol 273, R725–R730Google Scholar
  18. 18.
    Tkacs, N. C. and Levin, B. E. (2004). Obesity-prone rats have preexisting defects in their counterregulatory response to insulin-induced hypoglycemia. Am J Physiol Regul Integr Comp Physiol 287, R1110–R1115PubMedCrossRefGoogle Scholar
  19. 19.
    Wassink, A. M., Olijhoek, J. K., and Visseren, F. L. (2007), The metabolic syndrome: metabolic changes with vascular consequences. Eur J Clin Invest 37, 8–17PubMedCrossRefGoogle Scholar
  20. 20.
    Shafrir, E., Ziv, E., and Kalman, R. (2006). Nutritionally induced diabetes in desert rodents as models of type 2 diabetes: Acomys cahirinus (spiny mice) and Psammomys obesus (desert gerbil). ILAR J 47, 212–224PubMedGoogle Scholar
  21. 21.
    Kaiser, N., Nesher, R., Donath, M. Y., Fraenkel, M., Behar, V., Magnan, C., Ktorza, A., Cerasi, E., and Leibowitz, G. (2005). Psammomys obesus, a model for environment-gene interactions in type 2 diabetes. Diabetes 54, S137–S144PubMedCrossRefGoogle Scholar
  22. 22.
    Maislos, M., Medvedovskv, V., Sztarkier, I., Yaari, A., and Sikuler, E. (2006). Psammomys obesus (sand rat), a new animal model of non-alcoholic fatty liver disease. Diabetes Res Clin Pract 72, 1–5PubMedCrossRefGoogle Scholar
  23. 23.
    Barker, D. J. P., Bull, A. R., Osmond, C., and Simmonds, S. J. (1990). Fetal and placental size and risk of hypertension in adult life. Br Med J 301, 259–262CrossRefGoogle Scholar
  24. 24.
    Hales, C. N. and Barker, D. J. P. (2001). The thrifty phenotype hypothesis. Br Med Bull 60, 5–20PubMedCrossRefGoogle Scholar
  25. 25.
    McMillen, I. C. and Robinson, J. S. (2005), Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85, 571–633PubMedCrossRefGoogle Scholar
  26. 26.
    Ravelli, A. C., van der Meulen, J. H., Osmond, C., Barker, D. J., and Bleker, O. P. (1999). Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 70, 811–816PubMedGoogle Scholar
  27. 27.
    Ravelli, A. C. J., van der Meulen, J. H. P., Michels, R. P. J., Osmond, C., Barker, D. J. P., Hales, C. N., and Bleker, O. P. (1998). Glucose tolerance in adults after prenatal exposure to famine. Lancet 351, 173–177PubMedCrossRefGoogle Scholar
  28. 28.
    Pettit, D. J. and Knowler, W. C. (1998). Long-term effects of the intrauterine environment, birth weight, and breast-feeding in Pima Indians. Diabetes Care 21, B138–B141CrossRefGoogle Scholar
  29. 29.
    Ozanne, S. E. (2001). Metabolic programming in animals: Type 2 diabetes. Br Med Bull 60, 143–152PubMedCrossRefGoogle Scholar
  30. 30.
    Armitage, J. A., Khan, I. Y., Taylor, P. D., Nathanielsz, P. W., and Poston, L. (2004), Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals?. J Physiol (Lond) 561, 355–377CrossRefGoogle Scholar
  31. 31.
    Bavdekar, A., Yajnik, C., Fall, C., Bapat, S., Pandit, A., Deshpande, V., Bhave, S., Kellingray, S., and Joglekar, C. (1999). Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both?. Diabetes 48, 2422–2429PubMedCrossRefGoogle Scholar
  32. 32.
    McMillen, I. C., Adam, C. L., and Muhlhausler, B. S. (2005). Early origins of obesity: programming the appetite regulatory system. J Physiol 565, 9–17PubMedCrossRefGoogle Scholar
  33. 33.
    Hales, C. N. and Barker, D. J. P. (2001). The thrifty phenotype hypothesis: type 2 diabetes. Br Med Bull 60, 5–20PubMedCrossRefGoogle Scholar
  34. 34.
    Holemans, K., Verhaeghe, J., Dequeker, J., and Van Assche, F. A. (1996). Insulin sensitivity in adult female rats subjected to malnutrition during the perinatal period. J Soc Gynecol Investig 3, 71–77PubMedCrossRefGoogle Scholar
  35. 35.
    Thompson, N. M., Norman, A. M., Donkin, S. S., Shankar, R. R., Vickers, M. H., Miles, J. L., and Breier, B. H. (2007). Prenatal and postnatal pathways to obesity: different underlying mechanisms, different metabolic outcomes. Endocrinol Metab Clin North Am 148, 2345–2354Google Scholar
  36. 36.
    Ozanne, S. E., Jensen, C. B., Tingey, K. J., Storgaard, H., Madsbad, S., and Vaag, A. A. (2005). Low birthweight is associated with specific changes in muscle insulin-signalling protein expression. Diabetologia 48, 547–552PubMedCrossRefGoogle Scholar
  37. 37.
    Hales, C. N., Desai, M., Ozanne, S. E., and Crowther, N. J. (1996). Fishing in the stream of diabetes: from measuring insulin to the control of fetal organogenesis. Biochem Soc Trans 24, 341–350PubMedGoogle Scholar
  38. 38.
    Petry, C. J., Ozanne, S. E., Wang, C. L., and Hales, C. N. (1997). Early protein restriction and obesity independently induce hypertension in 1-year-old rats. Clin Sci (Lond) 93, 147–152Google Scholar
  39. 39.
    Snoeck, A., Remacle, C., Reusens, B., and Hoet, J. J. (1990). Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biol Neonate 57, 107–118PubMedCrossRefGoogle Scholar
  40. 40.
    Ozanne, S. E., Smith, G. D., Tikerpae, J., and Hales, C. N. (1996). Altered regulation of hepatic glucose output in the male offspring of protein-malnourished rat dams. Am J Physiol Endocrinol Metab 270, E559–E564Google Scholar
  41. 41.
    Ozanne, S. E., Nave, B. T., Wang, C. L., Shepherd, P. R., Prins, J., and Smith, G. D. (1997). Poor fetal nutrition causes long-term changes in expression of insulin signaling components in adipocytes. Am J Physiol Endocrinol Metab 273, E46–E51Google Scholar
  42. 42.
    Ozanne, S. E., Wang, C. L., Coleman, N., and Smith, G. D. (1996). Altered muscle insulin sensitivity in the male offspring of protein-malnourished rats. Am J Physiol Endocrinol Metab 271, E1128–E1134Google Scholar
  43. 43.
    Ozanne, S. E., Olsen, G. S., Hansen, L. L., Tingey, K. J., Nave, B. T., Wang, C. L., Hartil, K., Petry, C. J., Buckley, A. J., and Mosthaf-Seedorf, L. (2003). Early growth restriction leads to down regulation of protein kinase C zeta and insulin resistance in skeletal muscle. J Endocrinol 177, 235–241PubMedCrossRefGoogle Scholar
  44. 44.
    Ozanne, S. E., Jensen, C. B., Tingey, K. J., Storgaard, H., Madsbad, S., and Vaag, A. A. (2005). Low birthweight is associated with specific changes in muscle insulin-signalling protein expression. Diabetologia 48, 547–552PubMedCrossRefGoogle Scholar
  45. 45.
    Wadley, G. D., Siebel, A. L., Cooney, G. J., McConell, G. K., Wlodek, M. E., and Owens, J. A. (2008). Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult rat. Am J Physiol Endocrinol Metab 294, E861–E869PubMedCrossRefGoogle Scholar
  46. 46.
    Siebel, A. L., Mibus, A., De Blasio, M. J., Westcott, K. T., Morris, M. J., Prior, L., Owens, J. A., and Wlodek, M. E. (2008). Improved lactational nutrition and postnatal growth ameliorates impairment of glucose tolerance by uteroplacental insufficiency in male rat offspring. Endocrinology 149, 3067–3076PubMedCrossRefGoogle Scholar
  47. 47.
    Srinivasan, M., Katewa, S. D., Palaniyappan, A., Pandya, J. D., and Patel, M. S. (2006). Maternal high-fat diet consumption results in fetal malprogramming predisposing to the onset of metabolic syndrome-like phenotype in adulthood. Am J Physiol Endocrinol Metab 291, E792–E799PubMedCrossRefGoogle Scholar
  48. 48.
    Muhlhausler, B. S., Adam, C. L., Findlay, P. A., Duffield, J. A., and McMillen, I. C. (2006). Increased maternal nutrition alters development of the appetite-regulating network in the brain. FASEB J 20, 1257–1259PubMedCrossRefGoogle Scholar
  49. 49.
    Samuelsson, A.-M., Matthews, P. A., Argenton, M., Christie, M. R., McConnell, J. M., Jansen, E. H. J. M., Piersma, A. H., Ozanne, S. E., Twinn, D. F., Remacle, C., Rowlerson, A., Poston, L., and Taylor, P. D. (2008). Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension 51, 383–392PubMedCrossRefGoogle Scholar
  50. 50.
    Srinivasan, M., Aalinkeel, R., Song, F., Mitrani, P., Pandya, J. D., Strutt, B., Hill, D. J., and Patel, M. S. (2006). Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype. Am J Physiol Endocrinol Metab290, E129–E134PubMedCrossRefGoogle Scholar
  51. 51.
    Cerf, M. E., Williams, K., Chapman, C. S., and Louw, J. (2007). Compromised beta-cell development and beta-cell dysfunction in weanling offspring from dams maintained on a high-fat diet during gestation. Pancreas 34, 347–353PubMedCrossRefGoogle Scholar
  52. 52.
    Muhlhausler, B. S., Roberts, C. T., McFarlane, J. R., Kauter, K. G., and McMillen, I. C. (2002). Fetal leptin is a signal of fat mass independent of maternal nutrition in ewes fed at or above maintenance energy requirements. Biol Reprod 67, 493–499PubMedCrossRefGoogle Scholar
  53. 53.
    Muhlhausler, B. S., Duffield, J. A., and McMillen, I. C. (2007). Increased maternal nutrition stimulates peroxisome proliferator activated receptor-{gamma} (PPAR{gamma}), adiponectin and leptin mRNA expression in adipose tissue before birth. Endocrinology 148, 878–885PubMedCrossRefGoogle Scholar
  54. 54.
    Kasser, T. R., Martin, R. J., and Allen, C. E. (1981). Effect of gestational alloxan diabetes and fasting on fetal lipogenesis and lipid deposition in pigs. Biol Neonate 40, 105–112PubMedCrossRefGoogle Scholar
  55. 55.
    Ezekwe, M. O. and Martin, R. J. (1980). The effects of maternal alloxan diabetes on body composition, liver enzymes and metabolism and serum metabolites and hormones of fetal pigs. Horm Metab Res 12, 136–139PubMedCrossRefGoogle Scholar
  56. 56.
    Bayol, S. A., Simbi, B. H., Bertrand, J. A., and Stickland, N. C. (2008). Offspring from mothers fed a ‘junk food’ diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females. J Physiol 586, 3219–3230PubMedCrossRefGoogle Scholar
  57. 57.
    Padoan, A., Rigano, S., Ferrazzi, E., Beaty, B. L., Battaglia, F. C., and Galan, H. L. (2004). Differences in fat and lean mass proportions in normal and growth-restricted fetuses. Am J Obstet Gynecol 191, 1459–1464PubMedCrossRefGoogle Scholar
  58. 58.
    Crescenzo, R., Samec, S., Antic, V., Rohner-Jeanrenaud, F., Seydoux, J., Montani, J.-P., and Dulloo, A. G. (2003). A role for suppressed thermogenesis favoring catch-up fat in the pathophysiology of catch-up growth. Acta Paediatr 52, 1090–1097Google Scholar
  59. 59.
    Ibanez, L., Ong, K., Dunger, D. B., and de Zegher, F. (2006). Early development of adiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children. J Clin Endocrinol Metab 91, 2153–2158PubMedCrossRefGoogle Scholar
  60. 60.
    Jaquet, D., Gaboriau, A., Czernichow, P., and Levy-Marchal, C. (2000). Insulin resistance early in adulthood in subjects born with intrauterine growth retardation. J Clin Endocrinol Metab 85, 1401–1406PubMedCrossRefGoogle Scholar
  61. 61.
    Ozanne, S. E. (2001). Metabolic programming in animals. Br Med Bull 60, 143–152PubMedCrossRefGoogle Scholar
  62. 62.
    Kind, K. L., Clifton, P. M., Grant, P. A., Owens, P. C., Sohlstrom, A., Roberts, C. T., Robinson, J. S., and Owens, J. A. (2003). Effect of maternal feed restriction during pregnancy on glucose tolerance in the adult guinea pig. Am J Physiol Regul Integr Comp Physiol 284, R140–R152PubMedGoogle Scholar
  63. 63.
    De Blasio, M. J., Gatford, K. L., McMillen, I. C., Robinson, J. S., and Owens, J. A. (2006). Placental restriction of fetal growth increases insulin action, growth and adiposity in the young lamb. Endocrinology 148, 1350–1358PubMedCrossRefGoogle Scholar
  64. 64.
    Alexander, G. (1978). Quantitative development of adipose tissue in foetal sheep. Aust J Biol Sci 31, 489–503PubMedGoogle Scholar
  65. 65.
    Merklin, R. J. (1973). Growth and distribution of human fetal brown fat. Anat Res 178, 637–646CrossRefGoogle Scholar
  66. 66.
    Højlund, K., Mogensen, M., Sahlin, K., and Beck-Nielsen, H. (2008), Mitochondrial dysfunction in type 2 diabetes and obesity. Endocrinol Metabol Clin North Am 37, 713–731CrossRefGoogle Scholar
  67. 67.
    Junien, C., Gallou-Kabani, C., Vigé, A., and Gross, M. S. (2005). Nutritional epigenomics: consequences of unbalanced diets on epigenetics processes of programming during lifespan and between generations. Ann Endocrinol (Paris) 66, S19–S28Google Scholar
  68. 68.
    Gallou-Kabani, C. and Junien, C. (2005). Nutritional epigenomics of metabolic syndrome: new perspective against the epidemic. Diabetes 54, 1899–1906PubMedCrossRefGoogle Scholar
  69. 69.
    Waterland, R. A., Travisano, M., Tahiliani, K. G., Rached, M. T., and Mirza, S. (2008).Methyl donor supplementation prevents transgenerational amplification of obesity. Int J Obes 32, 1373–1379CrossRefGoogle Scholar
  70. 70.
    Haslam, D. W. and James, W. P. (2005). Obesity. Lancet 366, 1197–1209PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Early Origins of Adult Health Research Group, Sansom Research InstituteUniversity of South AustraliaAdelaideAustralia

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