Advertisement

Journal of the American Aging Association

, Volume 23, Issue 2, pp 95–101 | Cite as

Effects of dietary restriction on insulin resistance in obese mice

  • Ritchie J. Feuers
  • Varsha G. Desai
  • F. X. Chen
  • Jerry D. Hunter
  • Peter H. Duffy
  • Ebenezer T. Oriaku
Article

Abstract

In many cases, development of insulin resistance has been linked to obesity and may contribute to mechanism of aging. The role of diet, irrespective of degree of obesity, in modulating insulin resistance and development of age degeneration disease remains uncertain. Lowered blood glucose levels are commonly associated with diet restriction (DR), which is an intervention shown to successfully retard aging and age associated disease. The effects of DR on blood glucose and insulin resistance were measured in yellow obese (Avy/A), lean black (a/a) mice and in another common inbred strain (B6C3F1) (at three different ages). The yellow obese mice become diabetic as a result of an insulin receptor defect which is not clearly understood. Insulin responses and radioinsulin binding were assayed in yellow obese and lean black mice fed either ad libitum (AL) or DR diets (YAL, BAL, YDR and YAL, respectively) at four different circadian intervals. The B6C3F1 controls were fed either AL (CAL) or DR (CDR) and measures were made at six circadian stages and three different ages. Within 23 days, DR produced a significant loss in body weight and a time-dependent 22–55% reduction in basal blood glucose levels in the yellow obese mice. Additionally, exogenous insulin produced circadian stage dependent (at the time of food intake) reductions in blood glucose in the YDR animals that were not present in YAL animals. 125I-Insulin binding in liver was increased nearly 2-fold in YDR and BDR mice during the time of day that animals were active and eating. 125I-Insulin binding was two-fold-higher in CDR mice at 4, 12 and >24 months of age. Binding decreased as a function of age in both the CAL and CDR animals. However, even in the >24 month group the CDR animals were found to have levels of binding that were as high as those found in younger CAL liver. The mechanism of action appears to be through resolution of insulin resistance by modulating an insulin receptor defect.

Keywords

Insulin Resistance Blood Glucose Level Diet Restriction Lower Blood Glucose Lower Blood Glucose Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alemzadeh, R., Jacob, W., and Pitukcheewanont, P: Antiobesity effect of diazoxide in obese Zucker rats. Metabolism: Clin. & Exper. 45(3):334–41, 1996.Google Scholar
  2. Cooney, GJ and Storlien, LH: Insulin action, thermogenesis and obesity. Baill. Clin. Endo. & Metab. 8(3): 481–507, 1994.CrossRefGoogle Scholar
  3. DeFronzo, RA: Pharmacologic therapyfor type 2 diabetes mellitus. Annals Internal Med. 131(4)281–303, 1999.Google Scholar
  4. Duffy, PH, Feuers, RJ, Leakey, JA, Turturro, A, and Hart, RW: Effect of Chronic Caloric Restriction on Physiological Variables Related to Energy Metabolism in the Male Fischer 344 Rat. Mech. Ageing Dev. 48: 117–133, 1989.PubMedCrossRefGoogle Scholar
  5. Duffy, PH, Feuers, RJ, and Hart, RW: Effect of chronic caloric restriction on the circadian regulation of physiological and behavioral variables in the male B5C3F1 mouse. Chronobiology International 7:291–303, 1990a.PubMedGoogle Scholar
  6. Duffy, PH, Feuers, RJ, Nakamura, K, Leakey, JEA, and Hart, RW: Effect of chronic caloric restriction on the synchronization of various physiological measures in old female Fischer 344 rats. Chronobiology International 7:113–124, 1990b.PubMedGoogle Scholar
  7. Duffy, PH. and Feuers, RJ: Biomarkers of Aging: Changes in Circadian Rhythms Related to the Modulation of Metabolic Output. Biomed. Environ. Sc. 4:182–191, 1991a.Google Scholar
  8. Duffy, PH, Feuers, RJ, Leakey, JEA, and Hart, RW: Chronic caloric restriction in old female mice: Changes in the circadian rhythms of physiological and behavioral variables. In: L. Fishbein (ed.) Bio. Eff. of Diet. Res, Springer-Verlag, NY, 245–263, 1991b.Google Scholar
  9. Ebling, P and Koivisto, VA: Physiological importance of dehydroepiandrosterone. Lancet 343:1479–1481, 1994.CrossRefGoogle Scholar
  10. Falkner, B and Michel, S: Obesity and other risk factors in children. Ethnicity & Disease 9(2):284–9, 1999.Google Scholar
  11. Feuers, RJ, Duffy, PH, Leakey, JEA, Turturro, A, Mittelstadt, RA, and Hart, RW: Effect of chronic caloric restriction on hepatic enzymes of intermediary metabolism in male Fischer 344 rats. Mech. Age Develop. 48: 179–189, 1989.CrossRefGoogle Scholar
  12. Feuers, RJ, Hunter, JD, Duffy, PH, Leakey, JEA., Hart, RW, and Scheving, LE: 125I-Insulin binding in liver and affects of insulin on glucose homeostasis in calorically restricted mice. Ann. Rev. Chronobiology 7: 95–98, 1990a.Google Scholar
  13. Feuers, RJ, Hunter, JD, Duffy, PH, Leakey, JEA, Hart, RW, and Scheving, LE: 125I-Insulin binding in liver and the influence of insulin on blood glucose in calorically restricted B6C3F1 male mice. In: A. Reinberg and M. Smolensky (eds.), Ann. Rev. of Chronopharmacology, Paragon Press, 189–192, 1990b.Google Scholar
  14. Feuers, RJ: The relationship of dietary restriction to circadian variation in physiological parameters and regulation of metabolism. Aging 3(4):399–401, 1991.PubMedGoogle Scholar
  15. Frame, LT, Hart, RW, and Leakey, JE: Caloric restriction as a mechanism mediating resistance to environmental disease. Env. Health Persp. 106 Suppl 1:313–24, 1998.Google Scholar
  16. Golay, A & Felber, JP: Evolution of obesity to diabetes. Diabete et Metab. 20(1):3–14, 1994.Google Scholar
  17. Grundy, SM: Multifactorial causation of obesity: implications for prevention. Am. J. Clin. Nutr. 67(3 Suppl):563S–72S, 1998.PubMedGoogle Scholar
  18. Halberg, F., Johnson, E.A., Nelson, W., Runge, W., and Sothern, R: Autorhythmometry — procedures for physiological self-measurements and their analysis. Physiol. Teach., 1:1–11, 1972.Google Scholar
  19. Hodge, AM and Zimmet, PZ: The epidemiology of obesity. Baill. Clin. Endo. and Metab. 8(3):577–599, 1994.CrossRefGoogle Scholar
  20. Hotamisligil, GS: The role TNF alpha and TNF receptors in obesity and insulin resistance. J. Int. Med. 245(6)621–5, 1999.CrossRefGoogle Scholar
  21. Hsueh, WA and Buchanan, TA: Obesity and hypertension. Endocr. & Metabol. Clin. of N. Am. 23(2): 405–427, 1994.Google Scholar
  22. Ilarde, A and Tuck, M: Treatment of non-insulin-dependent diabetes mellitus and its complications. A state of the art review. Drugs & Aging 4(6):470–491, 1994.Google Scholar
  23. Jha, RJ: Thiazolidinediones—the new insulin enhancers. Clin. and Exper. Hypertension (New York) 21(1–2): 157–66, 1999.CrossRefGoogle Scholar
  24. Johannsson, G & Bengtsson, BA: Growth hormone and metabolic syndrome. J. Endo. Invest. 22(5 Suppl): 41–6, 1999.Google Scholar
  25. Kopelman, PG: Hormones and obesity. Baill. Clin. Endo. and Metab. 8(3):549–575, 1994.CrossRefGoogle Scholar
  26. Lanoue, KF and Martin, LF: Abnormal A1 adenosine receptor function in genetic obesity. FASEB J. 8(1): 72–80, 1994.PubMedGoogle Scholar
  27. Leakey, JEA, Cunny, HC, Bazare, J, Webb, P, Lipscomb, JC, Slikker, W, Feuers, RJ, Duffy, PH, and Hart, RW: Effects of aging and caloric restriction on hepatic drug metabolizing enzymes in Fischer 344 rats. Mech. Age Develop. 48: 145–155, 1989.CrossRefGoogle Scholar
  28. Lebovitz, HE: Type 2 diabetes: an overview. Clinical Chemistry 45(8 Pt 2):1339–45, 1999.PubMedGoogle Scholar
  29. Maegawa, H and Kashiwagi, A: Molecular mechanism and clinical impact of insulin resistance in type 2 diabetes mellitus. Nippon Rinsho — Japanese J. of Clin. Med. 57(3):539–44, 1999.Google Scholar
  30. Masoro, EJ: Possible mechanisms underlying the antiaging actions of caloric restriction. Toxicologic Pathology 24(6):738–41, 1996.PubMedCrossRefGoogle Scholar
  31. McGarry, JD: Disordered metabolism in diabetes: have we underemphasized the fat component? J. Cell. Biochem. 55 Suppl:29–38, 1994.PubMedCrossRefGoogle Scholar
  32. Meehan, WP, Darwin, CH, Maalouf, NB, Buchanan, TA, and Saad, MF: Insulin and hypertension: are they related? Przegkad Lekarski 51(3):135–148, 1994.Google Scholar
  33. Roth, GS, Ingram, DK, and Lane, MA: Caloric restriction in primates: will it work and how will we know? J. Am. Ger. Soc. 47(7):896–903, 1999.Google Scholar
  34. Scheen, AJ & Luyckx, FH: Medical aspects of obesity. Acta Chirurgica Belgica 99(3)135–9, 1999.PubMedGoogle Scholar
  35. Shafrin, E: Development and consequences of insulin resistance-lessons from animals with hyperinsulinemia. Diabetes and Metab. 22(2): 122–131, 1996.Google Scholar
  36. Smith, U: Carbohydrates, fat, and insulin action. Am.J. of Clin. Nutr. 59(3 Suppl): 686S–689S, 1994.Google Scholar
  37. Weindruch, R and Wallford, RL: The retardation of aging and disease by dietary restriction. Charles C. Thomas, Springfield, IL, 1988.Google Scholar
  38. Weindruch, R, Lane, MA, Ingram, DK, Ershler, WB, and Roth, GS: Dietary restriction in rhesus monkeys: lymphopenia and reduced mitogen-induced proliferation in peripheral blood mononuclear cells. Aging 9(4):304–8, 1997.PubMedGoogle Scholar

Copyright information

© American Aging Association, Inc. 2000

Authors and Affiliations

  • Ritchie J. Feuers
    • 1
    • 2
  • Varsha G. Desai
    • 1
  • F. X. Chen
    • 4
  • Jerry D. Hunter
    • 5
  • Peter H. Duffy
  • Ebenezer T. Oriaku
    • 3
  1. 1.Division of Genetic and Reproductive ToxicologyNational Center for Toxicological ResearchJefferson
  2. 2.Department of AnatomyUniversity of Arkansas for Medical SciencesLittle Rock
  3. 3.College of Pharmacy and Pharmaceutical SciencesFlorida A & M UniversityTallahassee
  4. 4.Department of PediatricsGuangzhou UniversityGuangzhouP.R. China
  5. 5.Department of BiologyUniversity of Texas El PasoEl Paso

Personalised recommendations