Advertisement

Normal Glucose Homeostasis

  • John E. Gerich
  • Steven D. Wittlin
  • Christian Meyer
Chapter

Abstract

Plasma glucose values are normally maintained within a relatively narrow range throughout the day (70–170 mg/dl) despite wide fluctuations in the delivery (e.g. meals) and removal (e.g. exercise) of glucose from the circulation. Teleologically, this is consistent with the fact that hyperglycemia is to be avoided because of its potential to cause macro- and microvascular complications.1,2 Conversely, this is also consistent with the fact that hypoglycemia is to be avoided because it can injure the brain. Limitations in the availability of alternate fuels (e.g. ketone bodies) or in their transport across the blood brain barrier (e.g. free fatty acids [FFA]) make glucose the usual source of energy for the brain. After prolonged fasting, however, because of an increase in their circulating concentration, ketone bodies may be used by the brain.3

Keywords

Plasma Glucose Level Plasma Glucose Concentration Glucose Release Mixed Meal Meal Ingestion 
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.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin dependent diabetes mellitus. N Engl J Med 329: 977–986, 1993.CrossRefGoogle Scholar
  2. 2.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352: 837–853, 1998.CrossRefGoogle Scholar
  3. 3.
    Owen O, Morgan A, Kemp H, Sullivan J, Herrera M, Cahill G. Brain metabolism during fasting. J Clin Invest 46: 1589–1595, 1967.PubMedCrossRefGoogle Scholar
  4. 4.
    Gerich J. Glucose counterregulation and its impact on diabetes mellitus. Diabetes 37: 1608–1617, 1988.PubMedCrossRefGoogle Scholar
  5. 5.
    Meyer C, Dostou J, Nadkarni V, Gerich J. Effects of physiological hyperinsulinemia on systemic, renal and hepatic substrate metabolism. Am J Physiol 275: F915 - F921, 1998.PubMedGoogle Scholar
  6. 6.
    Magnusson I, Rothman D, Gerard D, Katz L, Shulman G. Contribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentration. Diabetes 44: 185–189, 1995.PubMedCrossRefGoogle Scholar
  7. 7.
    Stumvoll M, Chintalapudi U, Perriello G, Welle S, Gutierrez O, Gerich J. Uptake and release of glucose by the human kidney: postabsorptive rates and responses to epinephrine. J Clin Invest 96: 2528–2533, 1995.PubMedCrossRefGoogle Scholar
  8. 8.
    Cahill G. Starvation in man. N Engl J Med 282: 668–675, 1970.PubMedCrossRefGoogle Scholar
  9. 9.
    Havel R. Caloric homeostasis and disorders of fuel transport. N Engl J Med 287: 1186–1192, 1972.PubMedCrossRefGoogle Scholar
  10. 10.
    Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46: 3–10, 1997.PubMedCrossRefGoogle Scholar
  11. 11.
    McGarry J. Glucose-fatty acid interactions in health and disease. Am J Clin Nutr 67 (3 Suppl): 500S - 504S, 1998.PubMedGoogle Scholar
  12. 12.
    Consoli A, Kennedy F, Miles J, Gerich J. Determination of Krebs cycle metabolic carbon exchange in vivo and its use to estimate the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output in man. J Clin Invest 80: 1303–1310, 1987.PubMedCrossRefGoogle Scholar
  13. 13.
    Perriello G, Jorde R, Nurjhan N, Stumvoll M, Dailey G, Jenssen T, Bier D, Gerich J. Estimation of the glucose-alanine-lactate-glutamine cycles in postabsorptive man: role of the skeletal muscle. Am J Physiol 269: E443 - E450, 1995.PubMedGoogle Scholar
  14. 14.
    Gerich J. Control of glycaemia. Bailliere’s Clinical Endocrinology and Metabolism 7: 551–586, 1993.CrossRefGoogle Scholar
  15. 15.
    Stumvoll M, Meyer C, Mitrakou A, Nadkarni V, Gerich J. Renal glucose production and utilization: new aspects in humans. Diabetologia 40: 749–757, 1997.PubMedCrossRefGoogle Scholar
  16. 16.
    Landau B, Wahren J, Chandramouli V, Schuman W, Ekberg K, Kalhan S. Contributions of gluconeogenesis to glucose production in the fasted state. J Clin Invest 98: 378–385, 1996.PubMedCrossRefGoogle Scholar
  17. 17.
    Ekberg K, Landau B, Wajngot A, Chandramouli V, Efendic S, Brunengraber H, Wahren J. Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting. Diabetes 48: 292–298, 1999.PubMedCrossRefGoogle Scholar
  18. 18.
    Stumvoll M, Meyer C, Kreider M, Perriello G, Gerich J. Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal postabsorptive humans. Metabolism 47: 1227–1232, 1998.PubMedCrossRefGoogle Scholar
  19. 19.
    Stumvoll M, Meyer C, Perriello G, Kreider M, Welle S, Gerich J. Human kidney and liver gluconeogenesis: evidence for organ substrate selectivity. Am J Physiol 274: E817 - E826, 1998.PubMedGoogle Scholar
  20. 20.
    Krebs H, Speake R, Hems R. Acceleration of renal gluconeogenesis by ketone bodies and fatty acids. Biochem J 94: 712–720, 1965.PubMedGoogle Scholar
  21. 21.
    McMahon M, Marsh H, Rizza R. Comparison of the pattern of postprandial carbohydrate metabolism after ingestion of a glucose drink or a mixed meal. J Clin Endocrinol and Metab 68: 647–653, 1989.CrossRefGoogle Scholar
  22. 22.
    Dinneen S, Gerich J, Rizza R. Carbohydrate metabolism in noninsulindependent diabetes mellitus. N Engl J Med 327: 707–713, 1992.PubMedCrossRefGoogle Scholar
  23. 23.
    Beckmann N, Fried R, Turkalj I, Seelig J, Keller U, Stalder G. Noninvasive observation of hepatic glycogen formation in man by 13C MRS after oral and intravenous glucose administration. Magn Reson Med 29: 583–590, 1993.PubMedCrossRefGoogle Scholar
  24. 24.
    Petersen K, Cline G, Gerard D, Magnusson I, Rothman D, Shulman G. Contribution of net hepatic glycogen synthesis to disposal of an oral glucose load in humans. Metabolism 50: 598–601, 2001.PubMedCrossRefGoogle Scholar
  25. 25.
    Kelley D, Mitrakou A, Marsh H, Schwenk F, Benn J, Sonnenberg G, Archangeli M, Aoki T, Sorensen J, Berger M, Sonksen P, Gerich J. Skeletal muscle glycolysis, oxidation, and storage of an oral glucose load. J Clin Invest 81: 1563–1571, 1988.PubMedCrossRefGoogle Scholar
  26. 26.
    Kelley D, Mokan M, Veneman T. Impaired postprandial glucose utilization in non-insulin-dependent diabetes mellitus. Metabolism 43: 1549–1557, 1994.PubMedCrossRefGoogle Scholar
  27. 27.
    Meyer C, Dostou J, Welle S, Gerich J. Role of liver, kidney and skeletal muscle in the disposition of an oral glucose load. Diabetes 48(Suppl 1):A289, 1999(Abstract).Google Scholar
  28. 28.
    Butler P, Kryshak E, Rizza R. Mechanism of growth hormone-induced postprandial carbohydrate intolerance in humans. Am J Physiol 260: E513 - E520, 1991.PubMedGoogle Scholar
  29. 29.
    Ferrannini E, Bjorkman O, Reichard G, Pilo A, Olsson M, Wahren J, DeFronzo R. The disposal of an oral glucose load in healthy subjects: a quantitative study. Diabetes 34: 580–588, 1985.PubMedCrossRefGoogle Scholar
  30. 30.
    Jackson R, Roshania R, Hawa M, Sim B, DiSilvio L. Impact of glucose ingestion on hepatic and peripheral glucose metabolism in man: an analysis based on simultaneous use of the forearm and double isotope techniques. J Clin Endo and Metab 63: 541–549, 1986.CrossRefGoogle Scholar
  31. 31.
    McMahon M, Marsh H, Rizza R. Effects of basal insulin supplementation on disposition of a mixed meal in obese patients with NIDDM. Diabetes 38: 291–303, 1989.PubMedCrossRefGoogle Scholar
  32. 32.
    Mitrakou A, Kelley D, Mokan M, Veneman T, Pangburn T, Reilly J, Gerich J. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. N Engl J Med 326: 22–29, 1992.PubMedCrossRefGoogle Scholar
  33. 33.
    Taylor R, Magnusson I, Rothman D. Direct assessment of liver glycogen storage by 13C nuclear magnetic resonance spectroscopy and regulation of glucose homeostasis after a mixed meal in normal subjects. J Clin Invest 97: 126–132, 1996.PubMedCrossRefGoogle Scholar
  34. 34.
    Mitrakou A, Jones R, Okuda Y, Pena J, Nurjhan N, Field J, Gerich J. Pathway and carbon sources for hepatic glycogen repletion in the dog. Am J Physiol 260: E194–202, 1991.PubMedGoogle Scholar
  35. 35.
    Firth R, Bell P, Marsh H, Hansen I, Rizza R. Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues. J Clin Invest 77: 1525–1532, 1986.PubMedCrossRefGoogle Scholar
  36. 36.
    Taylor R, Price T, Katz L, Shulman R, Shulman G. Direct measurement of change in muscle glycogen concentration after a mixed meal in normal subjects. Am J Physiol 265: E224 - E229, 1993.PubMedGoogle Scholar
  37. 37.
    Marin P, Hogh-Kristiansen I, Jansson S, Krotkiewski M, Holm G, Bjorntorp P. Uptake of glucose carbon in muscle glycogen and adipose tissue triglycerides in vivo in humans. Am J Physiol 263: E473 - E480, 1992.PubMedGoogle Scholar
  38. 38.
    Radziuk J, Inculet R. The effects of ingested and intravenous glucose on forearm uptake of glucose and glucogenic substrate in normal man. Diabetes 32: 977–981, 1983.PubMedCrossRefGoogle Scholar
  39. 39.
    Ferrannini E, Wahren J, Felig P, DeFronzo R. The role of fractional glucose extraction in the regulation of splanchnic glucose metabolism in normal and diabetic man. Metabolism 29: 28–35, 1980.PubMedCrossRefGoogle Scholar
  40. 40.
    Kruszynska Y, Mulford M, Yu J, Armstrong D, Olefsky J. Effects of nonesterified fatty acids on glucose metabolism after glucose ingestion. Diabetes 46: 1586–1593, 1997.PubMedCrossRefGoogle Scholar
  41. 41.
    Owen O, Felig P, Morgan A, Wahren J, Cahill G. Liver and kidney metabolism during prolonged starvation. J Clin Invest 48: 574–583, 1969.PubMedCrossRefGoogle Scholar
  42. 42.
    Joseph S, Heaton N, Potter D, Pernet A, Umpleby M, Amiel S. Renal glucose production compensates for the liver during the anhepatic phase of liver transplantation. Diabetes 49: 450–456, 2000.PubMedCrossRefGoogle Scholar
  43. 43.
    Cersosimo E, Ferretti J, Sasvary D, Garlick P. Adrenergic stimulation of renal glucose release is impaired in type 1 diabetes. Diabetes 50 (Suppl 2): A54, 2001.Google Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • John E. Gerich
  • Steven D. Wittlin
  • Christian Meyer

There are no affiliations available

Personalised recommendations

Cite chapter

Buy options