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The Minipig as a Model for the Study of Aging in Humans

Selective Responses of Hormones Involved in Carbohydrate and Lipid Metabolism in Different Sexes

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Advances in Swine in Biomedical Research

Abstract

Both age and sex have been shown to affect lipid and carbohydrate metabolism in animals and humans. There is a gradual loss of glucose homeostasis and concomitant increase in insulin resistance with age. Carbohydrate and lipid metabolism in different metabolic conditions including obesity and noninsulin dependent diabetes mellitus (NIDDM), both of which are age dependent, are controlled by pancreatic, pituitary and adrenal hormones. Therefore, we assessed age related changes in plasma hormones in male and female Hormel miniature swine. Animals were fed an energy restricted cholesterol free, low fat stock diet postweaning. Animals were sacrificed at various ages, ranging from prepubertal, <0.5 yr; young, 0.5 to 2.0 yr; mature, 2 to 10 yr and old, >10 years. Levels of insulin, glucagon, adrenocorticotropic hormone (ACTH), Cortisol and androstenedione were measured by radioimmunoassay in plasma from both sexes. In addition, dehydroepiandrosterone-sulfate (DHEA-S), aldosterone and testosterone were measured in male swine. No effect of age nor sex was observed on plasma insulin and ACTH levels though an interaction was observed between age and sex for ACTH. Thus, with age, levels of ACTH tended to increase in males but decrease in females. Plasma glucagon was higher in males than females and showed age dependent increases in males but not in females. Plasma androstenedione was 3 to 5 fold higher in males than in females and the level was lower in mature male swine than either prepubertal or older swine. There were sex and age dependent changes in plasma Cortisol levels with an increase with age in males and a decrease with age in females. There were no age dependent changes in plasma DHEA-S and aldosterone levels in the males. Plasma testosterone levels were higher in prepubertal swine than in mature or older animals. In swine, both age and sex affect hormonal changes, which then impact on metabolic parameters controlled by hormones, notably carbohydrate and lipid metabolism. Energy restriction appears to have a beneficial effect in retarding the aging process and miniature swine can be used as a model for the study of aging in humans.

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References

  1. Hsu, C.K., 1982, Uses of pigs in biomedical research: strengths and limitations, in: Pig Model for Biomedical Research, (H.R. Roberts, and W.J. Dodds, eds.), Pig Research Institute of Taiwan, Miaoli, Taiwan, Republic of China, pp. 3–10.

    Google Scholar 

  2. Pond, W.G., 1991, Of pigs and people, in: Swine Nutrition (E.R. Miller, D.E. Ullrey, and A.J. Lewis, eds.), Butterworth-Heinemann, Boston, pp.3–23.

    Google Scholar 

  3. Tumbleson, M.E. (ed.), 1986, Swine in Biomedical Research, Volumes 1, 2 and 3. Plenum Press, New York.

    Google Scholar 

  4. Miller, E.R., D.E. Ullrey, and A.J. Lewis (eds.), 1991, Swine Nutrition, Butterworth-Heinemann, Boston.

    Google Scholar 

  5. Roberts, H.R., and W.J. Dodds (eds.), 1982, Pig Model for Biomedical Research, Pig Research Institute of Taiwan, Miaoli, Taiwan, Republic of China.

    Google Scholar 

  6. Bustad, L.K., and R.O. McClellan (eds.), 1966, Swine in Biomedical Research, Frayn, Seattle.

    Google Scholar 

  7. Yu, B.P., Suescun, E.A., and Yang, S.Y., 1992, Effect of age-related lipid peroxidation on membrane fluidity and phospholipase A2: Modulation by dietary restriction, Mech. Age. Devel. 65:17–33.

    Article  CAS  Google Scholar 

  8. Laganiere, S., and Yu, B.P., 1993, Modulation of membrane phospholipid fatty acid composition by age and food restriction, Gerontology 39:7–18.

    Article  PubMed  CAS  Google Scholar 

  9. Masoro, E.J., 1990, Animal models in aging research, in: Handbook of the Biology of Aging, 3rd ed. (E.L. Schneider and J.W. Rowe, eds.), Academic Press, San Diego, pp. 72–94.

    Chapter  Google Scholar 

  10. Fernandes, G., 1995, Effects of calorie restriction and omega-3 fatty acids on autoimmunity and aging, Nutr. Rev. 53:572–579.

    Google Scholar 

  11. Liepa, G.U., Masoro, E.J., Bertrand, H.A., and Yu, B.P., 1980, Food restriction as a modulator of age-related changes in serum lipids, Am. J. Physiol. 238:E253–E257.

    PubMed  CAS  Google Scholar 

  12. Choi, J.H., and Yu, B.P., 1989, The effect of food restriction on kidney membrane structures of aging rats, Age 12:133–136.

    Article  CAS  Google Scholar 

  13. Masoro, E.J., 1985, Nutrition and aging: a current assessment. J. Nutr. 115:842–848.

    PubMed  CAS  Google Scholar 

  14. Yu, B.P., 1994, How diet influences the aging process of the rat, Proc. Soc. Exp. Biol. Med. 205:97–105.

    PubMed  CAS  Google Scholar 

  15. Rao, G., Xia, E., Nadakavukaren, M.J., and Richardson, A., 1990, Effect of dietary restriction on the age-dependent changes in the expression of antioxidant enzymes in rat liver, J. Nutr. 120:602–609.

    PubMed  CAS  Google Scholar 

  16. Masoro, E.J., 1992, Retardation of aging process by food restriction: an experimental tool, Am. J. Clin. Nutr. 52:1520S–1522S.

    Google Scholar 

  17. Ausman, L.M., and Russel, R.M., 1990, Nutrition and aging, in: Handbook of the Biology of Aging, 3rd ed. (E.L. Schneider and J.W. Rowe, eds.), Academie Press, Inc., San Diego, pp. 384–406.

    Chapter  Google Scholar 

  18. Masoro, E.J., 1992, A dietary key to uncovering aging processes, News Physiol Sci. 7:157–160.

    Google Scholar 

  19. Masoro, E.J., 1991, Animal models in aging research, in: Handbook of the Biology of Aging, 3rd ed. (E.L. Schneider and J.W. Rowe, eds.), Academic Press, San Diego, pp. 72–94.

    Google Scholar 

  20. Kagawa, Y., 1978, Impact of westernization on the nutrition of Japanese: Changes in physique, cancer, longivity, and centenarians, Prev. Med. 7:205–217.

    Article  PubMed  CAS  Google Scholar 

  21. Lopez, S.A., 1984, Metabolic and endocrine factors in aging, in: Risk Factors for Senility (H. Rothschild, and C.F. Chapman, eds.), Oxford University Press, New York, pp. 205–219.

    Google Scholar 

  22. Bhathena, S.J., Berlin, E., Judd, J., Nair, P.P., Kennedy, B.W., Jones, J., Smith, P.M., Jones, Y., Taylor, P.R., and Campbell, W.S., 1989, Hormones regulating lipid and carbohydrate metabolism in premenopausal women: modulation by dietary lipids, Am. J. Clin. Nutr. 49:752–757.

    PubMed  CAS  Google Scholar 

  23. Bhathena, S.J., Berlin, E., Judd, J.T., Kim, Y.C., Law, J.S., Bhagavan, H.N., Ballard-Barbash, R., and Nair, P.P., 1991, Effects of omega-3 fatty acids and vitamin E on hormones involved in carbohydrate and lipid metabolis in men, Am. J. Clin. Nutr. 54:684–686.

    PubMed  CAS  Google Scholar 

  24. Owens, P.C., Conlon, M.A., Campbell, R.G., Johnson, F.J., King, R., and Ballard, F.J., 1991, Developmental changes in growth hormone, insulin-like growth factors (IGF-I and IGF-II) and IGF-binding proteins in plasma of young growing pigs, J. Endocrinol. 128:439–447.

    Article  PubMed  CAS  Google Scholar 

  25. Lee, C.Y., Bazer, F.W., Etherton, T.D., and Simmen, F.A., 1991, Ontogeny of insulin-like growth factors (IGF-I and IGF-II) and IGF-binding proteins in porcine serum during fetal and postnatal development, Endocrinology 128:2336–2344.

    Article  PubMed  CAS  Google Scholar 

  26. McCusker, R.H., Cohick, W.S., Busby, W.H., and Clemmons, D.R., 1991, Evaluation of the developmental and nutritional changes in porcine insulin-like growth factor-binding protein-1 and-2 serum levels by immunoassay, Endocrinology 129:2631–2638.

    Article  PubMed  CAS  Google Scholar 

  27. Klindt, J., and Stone, R.T., 1984, Porcine growth hormone and prolactin: Concentrations in the fetus and secretory patterns in the growing pig, Growth 48:1–5.

    PubMed  CAS  Google Scholar 

  28. Klindt, J., Porcine growth hormone and prolactin secretion: the first month of postnatal life, Growth 50:516–525.

    Google Scholar 

  29. Hausman, G.J., Campion, D.R., and Buonomo, F.C., 1991, Concentrations of insulin-like growth factors (IGF-I and IGF-II) in tissues of developing lean and obese pig fetuses, Growth Dev. Aging 55:43–52.

    PubMed  CAS  Google Scholar 

  30. Kosco, M.S., Bolt, D.J., Wheaton, J.E., Loseth, K.J., and Crabo, B.G., 1987, Endocrine responses in relation to compensatory testicular growth after neonatal hemicastration in boars, Biol. Reprod. 36:1177–1185.

    Article  PubMed  CAS  Google Scholar 

  31. Ford, J.J., and Schanbacher, B.D., 1977, Luteinizing hormone secretion and female lordosis behavior in male pigs, Endocrinology 100:1033–1038.

    Article  PubMed  CAS  Google Scholar 

  32. Ford, J.J., 1983, Serum estrogen concentrations during postnatal development in male pigs, Proc. Soc. Exp. Biol. Med. 174:160–164.

    PubMed  CAS  Google Scholar 

  33. Buononmo, F.C., and Klindt, J., 1993, Ontogeny of growth hormone (GH), insulin-like growth factors (IGF-I and IGF-II) and IGF-binding protein-2 (IGFBP-2) in genetically lean and obese swine, Domestic Anim. Endocrin. 10:257–265.

    Article  Google Scholar 

  34. Mersmann, H.J., 1991, Characteristics of obese and lean swine, in: Swine Nutrition (E.R. Miller, D.E. Ullrey, and A.J. Lewis, eds.), Butterworth-Heinemann, London, pp.75–89.

    Google Scholar 

  35. Althen, T.G., and Gerrits, R.J., 1976, Pituitary and serum growth hormone levels in Duroc and Yorkshire swine genetically selected for high and low backfat, J. Anim. Sci. 42:1490–1497.

    PubMed  CAS  Google Scholar 

  36. Mersmann, H.J., Pond, W.G., and Yen, J.T., 1982, Plasma glucose, insulin and lipids during growth of genetically lean and obese swine, Growth 46:189–198.

    PubMed  CAS  Google Scholar 

  37. Statistical Analysis System Institute, Inc., 1988, SAS/STAT user’s guide: vesion 6.03, Cary, NC, SAS Institute, Inc.

    Google Scholar 

  38. Andres, R., 1971, Aging and diabetes, Med. Clin. N Am. 55:835–846.

    PubMed  CAS  Google Scholar 

  39. Harris, M., 1982, The prevalence of diabetes, undiagnosed diabetes and impaired glucose tolerance in the United States, in: Genetic and Environmental Interactions in Diabetes Mellitus (H.S. Mehish, J. Hanna, and S. Baba, eds.), Excerpta Medica, Amsterdam, pp. 70–76.

    Google Scholar 

  40. Davidson, M.B., 1979, The effect of aging on carbohydrate metabolism: a review of English literature and a practical approach to the diagnosis of diabetes mellitus in the elderly, Metabolism 28:688–705.

    Article  PubMed  CAS  Google Scholar 

  41. Hershcopf, R.J., Elahi, D., Andres, R., Baldwin, H.L., Raizes, G.S., Schoeken, D.D., and Tobin, J.D., 1982, Longitudinal changes in serum cholesterol in men: an epidemilogic search for an etiology, J. Chronic Dis. 35:101–114.

    Article  PubMed  CAS  Google Scholar 

  42. Goldberg, A.P., and Hagberg, J.M., Physical exercise in the elderly, in: Handbook of the Biology of Aging, 3rd ed. (E.L. Schneider, and J.W. Rowe, eds.), Academic Press, San Diego, pp. 407–428.

    Google Scholar 

  43. Harman, D., 1993, Free radicals and age related diseases, in: Free Radicals in Aging (Yu, B.P., ed.), CRC Press, Boca Raton, pp. 206–222.

    Google Scholar 

  44. Floyd, R.E., 1993, Basic free radical biochemistry, in: Free Radicals in Aging (Yu, B.P., ed.), CRC Press, Boca Raton, pp. 40–55.

    Google Scholar 

  45. Pryor, W.A., 1987, The free radical theory of aging revisited: a critique and a suggested disease specific theory, in: Modern Biological Theories of Aging (H.R. Warner, R.N. Butler, R.L. Sprott, and E.L. Schneider, eds.), Raven Press, New York, pp. 89–112.

    Google Scholar 

  46. Exton-Smith, A.N., 1972, Physiological aspects of aging: relationship to nutrition, Am. J. Clin. Nutr. 25:853–859.

    PubMed  CAS  Google Scholar 

  47. Rowe, J.W., Minaker, K.L., Pallotta, J.A., and Flier, J.S., 1983, Characterization of the insulin resistance of aging, J. Clin. Invest. 71:1581–1587.

    Article  PubMed  CAS  Google Scholar 

  48. Fink, R.I., Kolterman, O.G., Griffin, J., and Olefoky, J.M., 1983, Mechanism of insulin resistance in aging, J. Clin. Invest. 71:15 23-1525.

    Article  Google Scholar 

  49. Cher, M., Bergman, R.N., Pacini, J., and Porte, D., Jr., 1985, Pathogenesis of age related glucose intolerance in man: insulin resistance and decreased beta-cell function, J. Clin. Endocrinol. Metab. 60:13–20.

    Article  Google Scholar 

  50. Harris, M.I., Hadden, W.C., Knowler, W.C., and Bennett, P.H., 1987, Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in US population aged 20–74 yr., Diabetes 36:523–534.

    Article  PubMed  CAS  Google Scholar 

  51. Werman, M.J., and Bhathena, S.J., 1993, Restricted food intake ameliorates the severity of copper deficiency in rats fed a copper deficient, high fructose diet, Med. Sci. Res. 21:309–310.

    CAS  Google Scholar 

  52. Saari, J.T., Johnson, W.T., Reeves, P.G., and Johnson, L.K., 1993, Amelioration of effects of severe dietary copper deficiency by food restriction in rats, Am. J. Clin. Nutr. 58:891–896.

    PubMed  CAS  Google Scholar 

  53. Werman, M.J., and Bhathena, S.J., 1996. Effects of changes in dietary energy density and the amount of fructose on indices of copper status and metabolic parameters in male rats. J. Clin. Biochem. In Press.

    Google Scholar 

  54. Chipalkatti, S., De, A.K., and Aiyar, A.S., 1983, Effect of diet restricition on some biochemical parameters related to aging in mice, J. Nutr. 113:944–950.

    PubMed  CAS  Google Scholar 

  55. Yu, B.P., Lee, D.W., Marler, C.G., and Choi, J.-H., 1990, Mechanism of food restriction: protection of cellular homeostasis, Proc. Soc. Exp. Biol. Med. 193:13–15.

    PubMed  CAS  Google Scholar 

  56. Johnson, B.C., and Good, R.A., 1990, Chronic dietary restriction and longevity, Proc. Soc. Exp. Biol. Med. 193:4–5.

    PubMed  CAS  Google Scholar 

  57. Fernandes, G., Venkatraman, J., Khare, A., Horbach, G.J.M.J., and Friedrichs, W., 1990, Modulation of gene expression in autoimmune disease and aging by food restriction and dietary lipids, Proc. Soc. Exp. Biol. Med. 193:16–22.

    PubMed  CAS  Google Scholar 

  58. Eaton, R.P., and Schade, D.S., 1982, Hormonal antagonism of insulin, in: Diabetes and Obesity (R.N. Brodoff, and S.J. Bleicher, eds.), Williams and Wilkins, Baltimore, pp. 27–34.

    Google Scholar 

  59. Bhathena, S.J., 1992, Fatty acids and diabetes, in: Fatty Acids in Foods and Their Health Implications (C.K. Chow, ed.), Marcel Dekker, New York, pp. 823–855.

    Google Scholar 

  60. Berlin, E., Banks, M.A., Bhathena, S.J., Peters, R.C., and Johnson, W.A., 1996, Aging and miniature swine heart and liver plasma membranes, in: Advances in Swine in Biomedical Research (M.E. Tumblson, and L.B. Schook, eds.), Plenum Press, New York, 581–593.

    Chapter  Google Scholar 

  61. Lee, A.T., and Cerami, A., 1991, Modifications of proteins and nucleic acids by reducing sugars:possible role in aging, in: Handbook of the Biology of Aging, 3rd ed. (E.L. Schneider, and J.W. Rowe, eds.), Academic Press, San Diego, pp. 116–130.

    Google Scholar 

  62. Migeon, C.J., Keller, A.R., Lawrence, B., and Shepard, T.H., 1957, Dehydroepiandrosterone and andros-terone levels in human plasma. Effect of age and sex, day to day and diurnal variations, J. Clin. Endocrinol. Metab. 17:1051–1062.

    Article  PubMed  CAS  Google Scholar 

  63. Barrett-Conner, E., Kahn, K.T., and Yen S.S.C., 1986, A prospective study of dehydroepiandrosterone sulfate, mortality and cardiovascular disease, N. Engl. J. Med. 315:1519–1524.

    Article  Google Scholar 

  64. Yen, T.T., Allan, J.A., Pearson, D.V., Acton, J.M., and Greenberg, M.M., 1977, Prevention of obesity in Avy/a mice by dehydroepiandrosterone, Lipids 12:409–413.

    Article  PubMed  CAS  Google Scholar 

  65. Coleman, D.L., Leiter, E.H., and Appleweig, N., 1984, Therapeutic effects of dehydroepiandrosterone metabolites in diabetes mutant mice (C57BL/KSJ-db/db), Endocrinology 115:239–243.

    Article  PubMed  CAS  Google Scholar 

  66. Coleman, D.L., Leiter E.H., and Schwitzer, R.W., 1982, Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice, Diabetes 31:830–833.

    Article  PubMed  CAS  Google Scholar 

  67. Gansler, T.S., Muller, S., and Geary, M.P., 1985, Chronic administration of dehydroepiandrosterone reduces pancreatic B-cell hyperplasia and hyperinsulinemia in genetically obese Zucker rats, Proc Soc. Exp. Biol. Med. 180:155–162.

    PubMed  CAS  Google Scholar 

  68. Wichmann, U., Wichmann, G., and Krause, W., 1984, Serum levels of testosterone precursors, testosterone and estradiol in 10 animal species, Exp. Clin. Endocrinol. 83:283–290.

    Article  PubMed  CAS  Google Scholar 

  69. Stone, B.A., and Seamark, R.F., 1985, Steroid hormones in uterine washings and in plasma of gilts between days 9 and 15 after oestrus and and between days 9 and 15 after coitus, J. Reprod. Fert. 75:209–221.

    Article  CAS  Google Scholar 

  70. Campion, D.R., McCusker, R.H., Buonomo, F.C., and Jones W.K., Jr., 1986, Effect of fasting neonatal piglets on blood hormone and metabolite profiles and on skeletal muscle metabolism, J. Anim. Sci. 63:1418–1427.

    PubMed  CAS  Google Scholar 

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Bhathena, S.J., Berlin, E., Johnson, W.A. (1996). The Minipig as a Model for the Study of Aging in Humans. In: Tumbleson, M.E., Schook, L.B. (eds) Advances in Swine in Biomedical Research. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5885-9_12

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