The Role of the Lymphoid System in the Regulation of the Blood Glucose Level

Abstract

Recent findings have led to a new hypothesis in which it is proposed that the immune system plays a role in regulating the increase in blood glucose levels after a meal. The relevant findings are: (1) the primary lymphoid tissue, the lymph nodes are mostly present within adipose tissue depots throughout the body (there are at least 12 such depots and about 10¹² lymphocytes, 99% of which are present in lymph nodes); (2) lymphocytes and other immune cells utilize glucose at a high rate but almost all of it is converted to lactate which accumulates in the cells prior to release; (3) glutamine, some of which is synthesized in muscle from glucose, is utilized at a high rate by immune cells, the end-product of which is mainly aspartate, which also accumulates in the cells prior to release; and (4) finally, there is a common blood supply to the lymph node and the adipose tissue depot and the blood flow through the depot and hence the node is increased after a meal. It is proposed that, after a meal, some of the absorbed glucose is taken up from the blood by the lymphocytes and converted to lactate and glutamine is converted to aspartate. These are released slowly into the blood from where they are removed and converted to glycogen by the liver. Hence the immune cells provide a temporary buffer for glucose in the form of lactate and aspartate and, in this way, restrict the rise in blood glucose during and after a meal.

lymphocytes - glucose homeostasis - gluconeogenesis

References

• 1 Ardawi MSM, Newsholme EA. Metabolism in lymphocytes and its importance in the immune response.  Essays Biochem. 1985;  21 1-43
• 2 Calder PC, Yacoob P. Glutamine and the immune system.  Amino Acids. 1999;  17 227-241
• 3 Ardawi MSM, Newsholme EA. Glutamine metabolism in lymphocytes of the rat.  Biochem J. 1983;  212 835-842
• 4 Newsholme P, Curi R, Pithon-Curi TC, Murphy CJ, Garcia C, Pires de Melo M. Glutamine metabolism by lymphocytes, macrophages, and neutrophils: Its importance in health and disease.  J Nutr Biochem. 1999;  10 316-324
• 5 Newsholme EA. Hypercatabolism: Metabolic causes and consequences.  Surgery. 1998;  16 190-192
• 6 Pond CM. The fats of life. Cambridge: Cambridge University Press 1998
• 7 Pond CM. Paracrine interactions of mammalian adipose tissue.  J Expt Zool. 2003;  295A 99-110
• 8 Pond CM. Paracrine relationship between adipose tissue and lymphoid tissue.  Trends in Immunol. 2003;  24 13-18
• 9 Calder PC. Fuel utilization by cells of the immune system.  Proc Nutr Soc. 1995;  54 65-82
• 10 Buttgereit F, Burmester GR, Brand MD. Bioenergetics of immune functions: fundamental and therapeutic aspects.  Immunol Today. 2000;  21 192-199
• 11 Pithon-Curi TC, Pires De Melo M, Curi R. Glucose and glutamine utilization by rat lymphocytes, monocytes and neutrophils in culture: a comparative study.  Cell Biochem Funct. 2004;  22 321-326
• 12 Maratou E, Dimitriadis G, Kollias A, Boutati E, Lambadiari V, Mitrou P, Raptis SA. Glucose transporter expression on the plasma membrane of resting and activated white blood cells.  Eur J Clin Invest. 2007;  37 282-290
• 13 Pond CM. Adipose tissue and the immune system.  Prostaglandins Leukot Essent Fatty Acids. 2005;  73 17-30
• 14 Coppack S, Fisher R, Gibbons G, Frayn K. Postprandial substrate deposition in human forearm and adipose tissue in vivo.  Clin Sci. 1990;  79 339-348
• 15 Frayn KN, Karpe F, Fielding BA, Macdonald IA, Coppack SW. Integra-tive physiology of human adipose tissue.  Int J Obesity. 2003;  27 875-888
• 16 Dimitriadis G, Mitrou P, Lambadiari V, Boutati E, Maratou E, Panagiotakos D, Koukkou E, Tzanela M, Thalassinos N, Raptis S. Insulin action in adipose tissue and muscle in hypothyroidism.  J Clin Endocrinol Metab. 2006;  91 4930-4937
• 17 Ferrannini E, Galvan A, Castaldelli A, Camastra S, Sironi A, Toschi E, Baldi S, Frascera S, Monzani F, Antonelli A, Nannipieri M, Mari A, Seghieri G, Natali A. Insulin: new roles for an ancient hormone.  Eur J Clin Invest. 1999;  29 842-852
• 18 Kahn BB, Flier JS. Obesity and insulin resistance.  J Clin Invest. 2000;  106 473-481
• 19 Wellen KE, Hotamisligil GS. Inflammation, stress and diabetes.  J Clin Invest. 2005;  115 1111-1119
• 20 Amar J, Perez L, Burcelin R, Chamontin B. Arteries, inflammation and insulin resistance.  J Hypertension. 2006;  24 ((Suppl)) S18-S20
• 21 Janowska J, Zahorska-Markiewicz B, Olszanecka-Glinianowicz M. Relationship between serum resistin concentration and proinflammatory cytokines in obese women with impaired and normal glucose tolerance.  Metabolism. 2006;  55 1495-1499
• 22 Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance.  J Clin Invest. 2006;  116 1793-1801
• 23 Boden G. Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver.  Curr Diab Rep. 2006;  6 177-181

Correspondence