Glucose Metabolism

  • Antonio Macciò
  • Clelia Madeddu
  • Giovanni Mantovani


In 1919, glucose intolerance became the earliest recognised metabolic abnormality in cancer patients. Prior to the development of severe malnutrition, patients with colon, gastric, sarcoma, endometrial, prostate, localised head, neck and lung cancer had many of the metabolic abnormalities of type II (non-insulin-dependent) diabetes mellitus. These metabolic abnormalities included glucose intolerance, an increase in both hepatic glucose production (HGP) and glucose recycling, and insulin resistance. In a study of over 600 cancer patients, a diabetic pattern of glucose tolerance test was noted in over one-third of the patients [1].


Cancer Cachexia Hepatic Glucose Production Advanced Cancer Patient Alpha Lipoic Acid Prevent Weight Loss 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Tayek JA (1992) A review of cancer cachexia and abnormal glucose metabolism in humans with cancer. J Am Coll Nutr 11:445–456PubMedGoogle Scholar
  2. 2.
    Mantovani G, Macciò A, Lai P et al (1998) Cytokine activity in cancer-related anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate. Semin Oncol 25(Suppl 6):45–52PubMedGoogle Scholar
  3. 3.
    Mantovani G, Macciò A, Massa E, Madeddu C (2001) Managing cancer-related anorexia/cachexia. Drugs 61:499–514PubMedCrossRefGoogle Scholar
  4. 4.
    Kotler DP (2000) Cachexia. Ann Intern Med 133:622–634PubMedGoogle Scholar
  5. 5.
    Glicksman AS, Rawson RW (1956) Diabetes and altered carbohydrate metabolism in patients with cancer. Cancer 9:1127–1134PubMedCrossRefGoogle Scholar
  6. 6.
    Werk EE Jr, Macgee J, Sholiton IJ (1964) Altered cortisol metabolism in advanced cancer and other terminal illnesses: excretion of 6-hydroxycortisol. Metabolism 13:1425–1438PubMedCrossRefGoogle Scholar
  7. 7.
    Lundholm K, Holm G, Schersten T (1978) Insulin resistance in patients with cancer. Cancer Res 38:4665–4670PubMedGoogle Scholar
  8. 8.
    Argiles JM, Lopez-Soriano FJ (1999) The role of cytokines in cancer cachexia. Med Res Rev 19:223–248PubMedCrossRefGoogle Scholar
  9. 9.
    Van der Poll T, Romijn JA, Endert E et al (1991) Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. Am J Physiol 261:E457–E465PubMedGoogle Scholar
  10. 10.
    Strassmann G, Fong M, Kenney JS, Jacob CO (1992) Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J Clin Invest 89:1681–1684PubMedGoogle Scholar
  11. 11.
    Gelin J, Moldawer LL, Lonnroth C et al (1991) Role of endogenous tumor necrosis factor alpha and interleukin 1 for experimental tumor growth and the development of cancer cachexia. Cancer Res 51:415–421PubMedGoogle Scholar
  12. 12.
    Noguchi Y, Yoshikawa T, Matsumoto A et al (1996) Are cytokines possible mediators of cancer cachexia? Surg Today 26:467–475PubMedCrossRefGoogle Scholar
  13. 13.
    Matthys P, Billiau A (1997) Cytokines and cachexia. Nutrition 13:763–770PubMedCrossRefGoogle Scholar
  14. 14.
    Laviano A, Russo M, Freda F, Rossi Fanelli F (2002) Neurochemical mechanisms for cancer anorexia. Nutrition 18:100–105PubMedCrossRefGoogle Scholar
  15. 15.
    Plata-Salaman CR (1998) Cytokine-induced anorexia. Behavioral, cellular, and molecular mechanisms. Ann NY Acad Sci 856:160–170PubMedCrossRefGoogle Scholar
  16. 16.
    Sonti G, Ilyin SE, Plata-Salaman CR (1996) Anorexia induced by cytokine interactions at pathophysiological concentrations. Am J Physiol 270:R1394–R1402PubMedGoogle Scholar
  17. 17.
    Morley JE, Silver AJ, Miller DK, Rubenstein LZ (1989) The anorexia of the elderly. Ann NY Acad Sci 575:50–58PubMedCrossRefGoogle Scholar
  18. 18.
    Jennische E, Skottner A, Hansson HA (1987) Satellite cells express the trophic factor IGF-1 in regenerating skeletal muscle. Acta Physiol Scand 129:9–15PubMedCrossRefGoogle Scholar
  19. 19.
    Poggi C, Le Marchand-Brustel Y, Zapf J et al (1979) Effects and binding of insulin-like growth factor I in the isolated soleus muscle of lean and obese mice: comparison with insulin. Endocrinology 105:723–730PubMedCrossRefGoogle Scholar
  20. 20.
    Yu KT, Czech MP (1984) The type I insulin-like growth factor receptor mediates the rapid effects of multiplication-stimulating activity on membrane transport systems in rat soleus muscle. J Biol Chem 259:3090–3095PubMedGoogle Scholar
  21. 21.
    Beguinot F, Kahn CR, Moses AC, Smith RJ (1985) Distinct biologically active receptors for insulin, insulin-like growth factor I, and insulin-like growth factor II in cultured skeletal muscle cells. J Biol Chem 260:15892–15898PubMedGoogle Scholar
  22. 22.
    Ng EH, Rock CS, Lazarus DD et al (1992) Insulinlike growth factor I preserves host lean tissue mass in cancer cachexia. Am J Physiol 262:R426–R431PubMedGoogle Scholar
  23. 23.
    Barbosa J, Bach FH (1987) Cell-mediated autoimmunity in type I diabetes. Diabetes Metab Rev 3:981–1004PubMedGoogle Scholar
  24. 24.
    Argiles JM, Lopez-Soriano J, Busquets S, Lopez-Soriano FJ (1997) Journey from cachexia to obesity by TNF. FASEBJ 11:743–751Google Scholar
  25. 25.
    Sethi JK, Hotamisligil GS (1999) The role of TNF alpha in adipocyte metabolism. Semin Cell Dev Biol 10:19–29PubMedCrossRefGoogle Scholar
  26. 26.
    Hauner H, Petruschke T, Russ Met al (1995) Effects of tumour necrosis factor alpha (TNF alpha) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture. Diabetologia 38:764–771PubMedCrossRefGoogle Scholar
  27. 27.
    Kern PA, Ranganathan S, Li C et al (2002) Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280:E745–E751Google Scholar
  28. 28.
    Memon RA, Feingold KR, Moser AH et al (1998) Regulation of fatty acid transport protein and fatty acid translocase mRNA levels by endotoxin and cytokines. Am J Physiol 274:E210–E217PubMedGoogle Scholar
  29. 29.
    Memon RA, Fuller J, Moser AH et al (1998) In vivo regulation of acyl-CoA synthetase mRNA and activity by endotoxin and cytokines. Am J Physiol 275:E64–E72PubMedGoogle Scholar
  30. 30.
    Hotamisligil GS, Arner P, Caro JF et al (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409–2415PubMedGoogle Scholar
  31. 31.
    Moller DE (2000) Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 11:212–217PubMedCrossRefGoogle Scholar
  32. 32.
    Strassmann G, Fong M, Kenney JS, Jacob CO (1992) Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J Clin Invest 89:1681–1684PubMedGoogle Scholar
  33. 33.
    Navarra P, Pozzoli G, Brunetti L et al (1992) Interleukin-1 beta and interleukin-6 specifically increase the release of prostaglandin E2 from rat hypothalamic expiants in vitro. Neuroendocrinology 56:61–68PubMedGoogle Scholar
  34. 34.
    Schwartz MW, Baskin DG, Kaiyala KJ, Woods SC (1999) Model for the regulation of energy balance and adiposity by the central nervous system. Am J Clin Nutr 69:584–596PubMedGoogle Scholar
  35. 35.
    Hukshorn CJ, Saris WH (2004) Leptin and energy expenditure. Curr Opin Clin Nutr Metab Care 7:629–633PubMedCrossRefGoogle Scholar
  36. 36.
    Leibel RL, Rosenbaum M, Hirsch J (1995) Changes in energy expenditure resulting from altered body weight. N Engl J Med 332:621–628PubMedCrossRefGoogle Scholar
  37. 37.
    Bornstein SR, Licinio J, Tauchnitz R et al (1998) Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion. J Clin Endocrinol Metab 83:280–283PubMedCrossRefGoogle Scholar
  38. 38.
    Zumbach MS, Boehme MW, Wahl P et al (1997) Tumor necrosis factor increases serum leptin levels in humans. J Clin Endocrinol Metab 82:4080–4082PubMedCrossRefGoogle Scholar
  39. 39.
    Mantovani G, Macciò A, Mura L et al (2000) Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites. J Mol Med 78:554–561PubMedCrossRefGoogle Scholar
  40. 40.
    Mantovani G, Macciò A, Madeddu C et al (2001) Serum values of proinflammatory cytokines are inversely correlated with serum leptin levels in patients with advanced stage cancer at different sites. J Mol Med 79:406–414PubMedCrossRefGoogle Scholar
  41. 41.
    Aleman MR, Santolaria F, Batista N et al (2002) Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition? Cytokine 19:21–26PubMedCrossRefGoogle Scholar
  42. 42.
    Simons JP, Schols AM, Campfield LA et al (1997) Plasma concentration of total leptin and human lung-cancer-associated cachexia. Clin Sci (Lond) 93:273–277Google Scholar
  43. 43.
    Rosenbaum M, Nicolson M, Hirsch J et al (1997) Effects of weight change on plasma leptin concentrations and energy expenditure. J Clin Endocrinol Metab 82:3647–3654PubMedCrossRefGoogle Scholar
  44. 44.
    Considine RV, Sinha MK, Heiman ML et al (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295PubMedCrossRefGoogle Scholar
  45. 45.
    Pi-Sunyer FX (2000) Overnutrition and undernutrition as modifiers of metabolic processes in disease states. Am J Clin Nutr 72:533S–537SPubMedGoogle Scholar
  46. 46.
    Havel PJ (2001) Peripheral signals conveying metabolic information to the brain: short-term and longterm regulation of food intake and energy homeostasis. Exp Biol Med (Maywood) 226:963–977Google Scholar
  47. 47.
    Havel PJ (2004) Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 53:S1443–S1451CrossRefGoogle Scholar
  48. 48.
    Keim NL, Stern JS, Havel PJ (1998) Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. Am J Clin Nutr 68:794–801PubMedGoogle Scholar
  49. 49.
    Dubuc GR, Phinney SD, Stern JS, Havel PJ (1998) Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism 47:429–434PubMedCrossRefGoogle Scholar
  50. 50.
    Mantovani G, Macciò A, Madeddu C et al (2002) Quantitative evaluation of oxidative stress, chronic inflammatory indices and leptin in cancer patients: correlation with stage and performance status. Int J Cancer 98:84–91PubMedCrossRefGoogle Scholar
  51. 51.
    Mueller WM, Stanhope KL, Gregoire F et al (2000) Effects of metformin and vanadium on leptin secretion from cultured rat adipocytes. Obes Res 8:530–539PubMedCrossRefGoogle Scholar
  52. 52.
    Salvemini F, Franze A, Iervolino A et al (1999) Enhanced glutathione levels and oxidoresistance mediated by increased glucose-6-phosphate dehydrogenase expression. J Biol Chem 274:2750–2757PubMedCrossRefGoogle Scholar
  53. 53.
    Mantovani G, Madeddu C, Macciö A et al (2004) Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative approach beyond current treatment. Cancer Epidemiol Biomarkers Prev 13:1651–1659PubMedGoogle Scholar
  54. 54.
    Mantovani G, Macciò A, Madeddu C et al (2003) The impact of different antioxidant agents alone or in combination on reactive oxygen species, antioxidant enzymes and cytokines in a series of advanced cancer patients at different sites: correlation with disease progression. Free Radie Res 37:213–223CrossRefGoogle Scholar
  55. 55.
    Mantovani G, Macciò A, Melis G et al (2000) Restoration of functional defects in peripheral blood mononuclear cells isolated from cancer patients by thiol antioxidants alpha-lipoic acid and N-acetyl cysteine. Int J Cancer 86:842–847PubMedCrossRefGoogle Scholar
  56. 56.
    Malmberg KJ, Lenkei R, Petersson M et al (2002) A short-term dietary supplementation of high doses of vitamin E increases T helper 1 cytokine production in patients with advanced colorectal cancer. Clin Cancer Res 8:1772–1778PubMedGoogle Scholar
  57. 57.
    Cemerski S, Cantagrel A, Van Meerwijk JP, Romagnoli P (2002) Reactive oxygen species differentially affect T cell receptor-signaling pathways. J Biol Chem 277:19585–19593PubMedCrossRefGoogle Scholar
  58. 58.
    Mantovani G, Macciò A, Madeddu C et al (2003) Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients: assessment of the most important laboratory indexes of cachexia and oxidative stress. J Mol Med 81:664–673PubMedCrossRefGoogle Scholar
  59. 59.
    Palacio A, Lopez M, Perez-Bravo F et al (2002) Leptin levels are associated with immune response in malnourished infants. J Clin Endocrinol Metab 87:3040–3046PubMedCrossRefGoogle Scholar
  60. 60.
    Faggioni R, Feingold KR, Grunfeld C (2001) Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 15:2565–2571PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2006

Authors and Affiliations

  • Antonio Macciò
    • 1
  • Clelia Madeddu
    • 2
  • Giovanni Mantovani
    • 2
  1. 1.Obstetrics and Ginecology UnitSirai HospitalCarboniaItaly
  2. 2.Department of Medical OncologyUniversity of CagliariCagliariItaly

Personalised recommendations