Physiology pp 291-303 | Cite as

Glucose Regulation and the RES

  • James P. Filkins


Ludwig Aschoff is duly recognized for introduction of a unifying terminology for the confederation of body macrophages—i.e., his reticuloendothelial system. Less well known is that he also drew attention to numerous physiological facets of the RES which impacted on the general metabolic functions of the body and thus he offered an alternate unifying term for the collection of local and wandering histiocytes—the histiocytic metabolic apparatus (Aschoff, 1924). Over the ensuing years the notion of a direct role for macrophages in body metabolism has faded along with the term histiocytic metabolic apparatus. Only in recent years has expanding knowledge of macrophage physiology and especially their secretion of regulatory molecules or monokines with metabolic capabilities, once again drawn attention to metabolic interrelationships which involve the RES.


Glucose Homeostasis Reticuloendothelial System Glucose Regulation Hepatic Gluconeogenesis Endotoxin Shock 
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. Adeleye, G. A., Al-Jibouri, L. M., Furman, B. L., and Parratt, J. R., 1981, Endotoxin-induced metabolic changes in the conscious, unrestrained rat, Circ. Shock 8:543.PubMedGoogle Scholar
  2. Agarwal, M. K., 1975, An integrative analysis of endotoxic reactions, Naturwissenschaften 62:167.CrossRefGoogle Scholar
  3. Agarwal, M. K., and Lazar, G., 1977, Metabolic basis of endotoxicosis, Microbios 20:183.PubMedGoogle Scholar
  4. Agarwal, M. K., Hoffman, W. W., and Rosen, F., 1969, The effect of endotoxin and thorotrast on inducible enzymes in the isolated, perfused rat liver, Biochim. Biophys. Acta 177:250.PubMedCrossRefGoogle Scholar
  5. Archer, L. T., White, G. L., Coalson, J. J., Beller, B. K., Elmore, O., and Hinshaw, L. B., 1978, Preserved liver function and leukocyte response in superlethal endotoxic shock, Circ. Shock 5:279.PubMedGoogle Scholar
  6. Aschoff, L., 1924, The reticulo-endothelial system, in: Lectures on Pathology, pp. 1-33, Hoeber, New York.Google Scholar
  7. Beisel, W. R., 1975, Metabolic responses to infection, Annu. Rev. Med. 26:9.PubMedCrossRefGoogle Scholar
  8. Berry, L. J., 1971, Metabolic effects of bacterial endotoxins, in: Bacterial Toxins, Vol. 5 (S. Kadis, G. Weinbaum, and S. J. Ajl, eds.), pp. 165–208, Academic Press, New York and London.Google Scholar
  9. Berry, L. J., 1975, Metabolic effects of endotoxins, in: Microbiology 1975 (D. Schlessinger, ed.), pp. 315–325, American Society of Microbiology, Washington, D.C.Google Scholar
  10. Berry, L. J., 1977, Bacterial toxins, CRC Crit. Rev. Toxicol. 239.Google Scholar
  11. Biozzi, G. B., Benacerraf, B., and Halpern, B. N., 1953, Quantitative study of the granulopectic activity of the reticuloendothelial system, Br. J. Exp. Pathol. 34:441.PubMedGoogle Scholar
  12. Blackard, W. G., Anderson, J. H., and Spitzer, J. J., 1976, Hyperinsulinism in endotoxin shock dogs, Metabolism 25:676.CrossRefGoogle Scholar
  13. Brodai, B. P., Assev, S., and Eeg-Larsen, N., 1971, Degradation studies of insulin in the isolated perfused rat liver, with and without blocked reticuloendothelial system, Horm. Metab. Res. 3:217.CrossRefGoogle Scholar
  14. Buchanan, B. J., and Filkins, J. P., 1976a, Insulin secretion and sensitization to endotoxin shock, Circ. Shock 3:223.Google Scholar
  15. Buchanan, B. J., and Filkins, J. P., 1976b, Insulin secretion and the carbohydrate metabolic alterations of endotoxemia, Circ. Shock 3:267.Google Scholar
  16. Buchanan, B. J., and Filkins, J. P., 1976c, Hypoglycemic depression of RES function, Am. J. Physiol. 231:265.PubMedGoogle Scholar
  17. Cornell, R. P., 1980, Mechanisms of acute hyperinsulinemia after Kupffer cell phagocytosis, Am. J. Physiol. 238:E276.PubMedGoogle Scholar
  18. Cornell, R. P., 1981, Basal insulin and glucagon responses to portal versus systemic venous administration of endotoxin in fasted rats, Physiologist 24:117.Google Scholar
  19. DeLustro, F., Sherer, G. K., and LeRoy, E. C., 1980, Human monocyte stimulation of fibroblast growth by a soluble mediator(s), J. Reticuloendothelial Soc. 6:519.Google Scholar
  20. Filkins, J. P., 1977, Depression of RES function and sensitization to endotoxin shock and hypoglycemia, J. Reticuloendothelial Soc. 20:461.Google Scholar
  21. Filkins, J. P., 1978, Phases of glucose dyshomeostasis in endotoxicosis, Circ. Shock 5:347.PubMedGoogle Scholar
  22. Filkins, J. P., 1979a, RES function and glucose homeostasis, in: Macrophages and Lymphocytes: Nature, Functions, and Interaction, Part A (M. R. Escobar and H. Friedman, eds.), pp. 391–402, Plenum Press, New York and London.Google Scholar
  23. Filkins, J. P., 1979b, Insulin-like activity (ILA) of a macrophage mediator on adipose tissue glucose oxidation, J. Reticuloendothelial Soc. 25:595.Google Scholar
  24. Filkins, J. P., 1979c, Role of the RES in lead salt sensitization to endotoxin shock, in: Macrophages and Lymphocytes: Nature, Functions, and Interaction, Part A (M. R. Escobar and H. Friedman, eds.), pp. 21–27, Plenum Press, New York and London.Google Scholar
  25. Filkins, J. P., 1980, Endotoxin-enhanced secretion of macrophage insulin-like activity, J. Reticuloendothelial Soc. 27:507.Google Scholar
  26. Filkins, J. P., 1981a, The reticuloendothelial system and metabolic homeostasis, in: Pathophysiology of the Reticuloendothelial System (B. M. Altura and T. M. Saba, eds.), pp. 93–110, Raven Press, New York.Google Scholar
  27. Filkins, J. P., 1981b, Serum immunoreactive (IRI) and non-suppressible insulin-like activity (NSILA) in endotoxin shock, Physiologist 23:37.Google Scholar
  28. Filkins, J. P., 1982, Effect of phentolamine on insulin levels and insulin responsiveness in endotoxicosis, Adv. Shock Res. 7:185.PubMedGoogle Scholar
  29. Filkins, J. P., and Buchanan, B. J., 1977, Depression of RES function and altered glucoregulation, J. Reticuloendothelial Soc. 21:389.Google Scholar
  30. Filkins, J. P., and Cornell, R. P., 1974, Depression of hepatic gluconeogenesis and the hypoglycemia of endotoxin shock, Am. J. Physiol. 227:778.PubMedGoogle Scholar
  31. Filkins, J. P., and Kober, P. M., 1981, Interrelations of RES endocytic and exocytic functions with glucose homeostasis in the pathogenesis of endotoxin shock, in: Homeostasis in Injury and Shock (A. G. B. Kovach, H. B. Stoner and J. J. Spitzer, eds.), pp. 171–180, Pergamon Press, Elmford Park, New York.Google Scholar
  32. Filkins, J. P., and Viray, R. E., 1982, Comparison of immunoreactive (IRI) and non-suppressible insulin-like activity (NSILA) in endotoxic versus septic lock, Fed. Proc. 41:1606.Google Scholar
  33. Filkins, J. P., and Yelich, M. R., 1980, RES function and geguliegulation in endotoxicosis, in: The Reticuloendothelial System and the Pathogenesis of Liver Disease (H. Liehr and M. Grün, eds.), pp. 89–98, Elsevier/North Holland Biomedical Press, Amsterdam.Google Scholar
  34. Filkins, J. P., and Yelich, M. R., 1982, Mechanisms of hyperinsulinemia after RES phagocytosis, Am. J. Physiol. 242:E115.PubMedGoogle Scholar
  35. Filkins, J. P., Janusek, L. W., and Yelich, M. R., 1980, The role of insulin and insulin-like activity in the hypoglycemic response to endotoxin, in: Bacterial Endotoxins and Host Response (M. K. Agarwal, ed.), pp. 361–379, Elsevier/North Holland Biomedical Press, Amsterdam.Google Scholar
  36. Fine, J., 1965, Shock and peripheral circulatory insufficiency, in: Handbook of Physiology, Circulation, Vol. III, pp. 2037–2069, American Physiological Society, Washington, D.C.Google Scholar
  37. George, D. T., Abeles, F. B., Mapes, C. A., Sobocinski, P. Z., Zenser, T. V., and Powanda, M. C., 1977, Effect of leukocytic endogenous mediators on endocrine pancreas secretory responses, Am. J. Physiol. 233:E240.PubMedGoogle Scholar
  38. Giger, O., and McCallum, R. E., 1976, Response of mouse liver glycogen cycle enzymes to endotoxin treatment, Am. J. Physiol. 231:1285.PubMedGoogle Scholar
  39. Glenn, K. C., and Ross, R., 1981, Human monocyte-derived growth factor(s) for mesenchymal cells: Activation of secretion by endotoxin and concanavalin A, Cell 25:603.PubMedCrossRefGoogle Scholar
  40. Goldfarb, R. D., Weber, P., and Eisenman, J., 1981, The effect of leucine on plasma insulin following endotoxin shock in the rat, Circ. Shock 8:343.PubMedGoogle Scholar
  41. Gross, R. L., and Newberne, P. M., 1980, Role of nutrition in immunologic function, Physiol. Rev. 60:188.PubMedGoogle Scholar
  42. Gudewicz, P. W., and Filkins, J. P., 1974, Glycogen metabolism in macrophages, J. Reticuloendothelial Soc. 16:1.Google Scholar
  43. Gudewicz, P. W., and Filkins, J. P., 1976, Glycogen metabolism in inflammatory macrophages, J. Reticuloendothelial Soc. 19:147.Google Scholar
  44. Hadbavny, A. M., Buchanan, B. J., and Filkins, J. P., 1978, Insulin and the glucoregulatory alterations of RES depression, J. Reticuloendothelial Soc. 24:57.Google Scholar
  45. Hamosh, M., and Shapiro, B., 1960, The mechanism of glycogenolytic action of endotoxin, Br. J. Exp. Pathol. 41:372.PubMedGoogle Scholar
  46. Heggers, J. P., Robson, M. C., Jennings, P. B., and Fariss, B. L., 1976, Effects of glucose therapy on experimental Escherichia coli septicemia, J. Surg. Res. 20:33.PubMedCrossRefGoogle Scholar
  47. Hinshaw, L. B., 1976, Concise review: The role of glucose in endotoxic shock, Circ. Shock 3:1.Google Scholar
  48. Hinshaw, L. B., Peyton, M. D., Archer, L. T., Black, M. B., Coalson, J. J., and Greenfield, L. J., 1974, Prevention of death in endotoxin shock by glucose administration, Surg. Gynecol. Obstet. 139:851.PubMedGoogle Scholar
  49. Holtzman, S., Schuler, J. J., Earnst, W., Erve, P. R., and Schumer, W., 1974, Carbohydrate metabolism in endotoxemia, Circ. Shock 1:99.Google Scholar
  50. Kober, P. M., and Filkins, J. P., 1981, Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver, Adv. Shock Res. 5:47.PubMedGoogle Scholar
  51. Kober, P. M., Thomas, J. X., and Filkins, J. P., 1981, Correlation of hemodynamics to glucose and insulin changes in endotoxicosis, Fed. Proc. 40:572.Google Scholar
  52. Kun, E., and Miller, C. P., 1948, Effect of bacterial endotoxins on carbohydrate metabolism in rabbits, Proc. Soc. Exp. Biol. Med. 67:221.PubMedGoogle Scholar
  53. Leach, G. J., and Spitzer, J. A., 1981, Endotoxin-induced alterations in glucose transport in isolated adipocytes, Biochim. Biophys. Acta 643:71.Google Scholar
  54. Lowitt, S., Szentivanyi, A., and Williams, J. F., 1981, Endotoxin inhibition of dexamethasone induction of tryptophan oxygenase in suspension culture of isolated rat parenchymal cells, Biochem. Pharmacol. 30:1999.PubMedCrossRefGoogle Scholar
  55. McCallum, R. E., 1980, Mediated inhibition of hepatic gluconeogenesis by endotoxin, in: Microbiology 1980 (D. Schlessinger, ed.), pp. 87–90, American Society of Microbiology, Washington, D.C.Google Scholar
  56. McCallum, R. E., 1981, Hepatocyte-Kupffer cell interactions in the inhibition of hepatic gluconeogenesis by bacterial endotoxin, in: Pathophysiological Effects of Endotoxins at the Cellular Level (J. A. Majde and R. J. Person, eds.), pp. 99–113, Alan R. Liss, Inc., New York.Google Scholar
  57. McCallum, R. E., and Berry, L. J., 1973, Effects of endotoxin on gluconeogenesis, glycogen synthesis, and liver glycogen synthase in mice, Infect. Immun. 7:642.PubMedGoogle Scholar
  58. Manny, J., Rabinovici, N., and Schiller, M., 1977, Insulin response to continuous glucose load in endotoxin shock in the dog, Surg. Gynecol. Obstet. 145:198.PubMedGoogle Scholar
  59. Menten, M. L., and Manning, H. M., 1923, Blood sugar studies on rabbits infected with organisms of the enteritidis-paratyphoid B group, J. Med. Res. 44:675.Google Scholar
  60. Moore, R. N., Goodrum, K. J., and Berry, L. J., 1976, Mediation of endotoxin effects by macrophages, J. Reticuloendothelial Soc. 19:187.Google Scholar
  61. Powanda, M. C., Bostian, K. A., Dinterman, R. E., Fee, W. G., Fowler, J. P., Hauer, E. C., and White, J. P., 1980, Phagocytosis and the metabolic sequelae of infection, J. Reticuloendothelial Soc. 27:67.Google Scholar
  62. Rayfield, E. J., Curnow, R. T., Reinhard, D., and Kochicheril, N. M., 1977, Effects of acute endotoxemia on glucoregulation in normal and diabetic subjects, J. Clin. Endocrinol. Metab. 45:513.PubMedCrossRefGoogle Scholar
  63. Raymond, R. M., Harkema, J. M., and Emerson, T. E., Jr., 1981, Direct effects of gram-negative endotoxin on skeletal muscle glucose uptake, Am. J. Physiol. 240:H342.PubMedGoogle Scholar
  64. Romanosky, A. J., Bagby, B. J., Bockman, E. L., and Spitzer, J. J., 1980, Increased muscle glucose uptake and lactate release after endotoxin administration, Am. J. Physiol. 239:E311.PubMedGoogle Scholar
  65. Senterfitt, V. C., and Shands, J. W., Jr., 1978, Endotoxin induced metabolic alterations in BCG infected (hyperreactive) mice, Proc. Soc. Exp. Biol. Med. 159:69.PubMedGoogle Scholar
  66. Shands, J. W., Jr., Miller, V., and Marten, H., 1969a, The hypoglycemic activity of endotoxin. I. Occurrence in animals hyperreactive to endotoxin, Proc. Soc. Exp. Biol. Med. 130:413.PubMedGoogle Scholar
  67. Shands, J. W., Jr., Miller, V., and Senterfitt, V., 1969b, Hypoglycemic activity of endotoxin. II. Mechanism of the phenomenon in BCG-infected mice, J. Bacteriol. 98:494.PubMedGoogle Scholar
  68. Shands, J. W., Jr., Senterfitt, V. C., and Miller, V., 1971, Endotoxin-induced insulin sensitivity in BCG infected mice, Proc. Soc. Exp. Biol. Med. 136:983.PubMedGoogle Scholar
  69. Spitzer, J. J., Wagner, G. G., and Blackard, W. G., 1976, The effect of glucose infusion on selected hemodynamic variables and plasma insulin concentration in dogs after E. coli endotoxin administration, Circ. Shock 3:31.Google Scholar
  70. Yelich, M. R., and Filkins, J. P., 1980a, Mechanisms of hyperinsulinemia in the endotoxic rat, Am. J. Physiol. 239:E156.PubMedGoogle Scholar
  71. Yelich, M. R., and Filkins, J. P., 1980b, Effect of arginine on lethality and insulin secretion in endotoxicosis, Circ. Shock 7:200.Google Scholar
  72. Yelich, M. R., and Filkins, J. P., 1981, Role of Ca++ in the insulin hypersecretion of the endotoxic pancreas, Circ. Shock 8:224.Google Scholar
  73. Zeckwer, I. T., and Goodell, H., 1925a, Blood sugar studies. I. Rapid alterations in the blood sugar levels of rabbits as result of intravenous injections of killed bacteria of various types, J. Exp. Med. 42:43.PubMedCrossRefGoogle Scholar
  74. Zeckwer, I. T., and Goodell, H., 1925b, Blood sugar studies. II. Blood sugar changes in fatal bacterial anaphylaxis in the rabbit, J. Exp. Med. 42:57.PubMedCrossRefGoogle Scholar
  75. Zwadyk, P., Jr., and Snyder, I. S., 1973, Effects of endotoxin on hepatic glycogen metabolism in vitro, Proc. Soc. Exp. Biol. Med. 142:299.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • James P. Filkins
    • 1
  1. 1.Department of Physiology, Stritch School of MedicineLoyola University of ChicagoMaywoodUSA

Personalised recommendations