Diabetes, Vol 46, Issue 1 70-76, Copyright © 1997 by American Diabetes Association

ARTICLES

Counterregulation in peripheral tissues: effect of systemic hypoglycemia on levels of substrates and catecholamines in human skeletal muscle and adipose tissue

DG Maggs, R Jacob, F Rife, S Caprio, WV Tamborlane and RS Sherwin
Section of Endocrinology, Yale University, New Haven, Connecticut 06510, USA.

We used microdialysis to distinguish the effects of hyperinsulinemia and hypoglycemia on glucose, gluconeogenic substrate, and catecholamine levels in adipose and muscle extracellular fluid (ECF). Ten lean humans (six males and four females) were studied during baseline and hyperinsulinemic (3 mU x kg-1 x min-1 for 3 h) euglycemia (5.0 mmol/l) and hypoglycemia (2.8 mmol/l). In muscle and adipose, basal ECF glucose was lower (muscle, 3.5 +/- 0.2 mmol/l; adipose tissue, 3.3 +/- 0.2 mmol/l) and lactate was higher (muscle, 2.2 +/- 0.2 mmol/l; adipose, 1.5 +/- 0.3 mmol/l) than respective plasma values (glucose, 4.9 +/- 0.1 mmol/l; lactate, 0.7 +/- 0.1 mmol/l), whereas alanine was higher in muscle ECF (379 +/- 22 micromol/l) than adipose tissue (306 +/- 22 micromol/l) and plasma (273 +/- 33 micromol/l). Plasma catecholamines (unchanged during euglycemia) rose during hypoglycemia with epinephrine, increasing approximately fivefold more than norepinephrine. In contrast, the hypoglycemia-induced increments in muscle dialysate norepinephrine and epinephrine were similar, suggesting local generation of norepinephrine. Compared with euglycemia, hypoglycemia produced a greater increase in lactate and a smaller reduction in alanine in muscle ECF, whereas hypoglycemia caused a greater relative fall in ECF glucose concentrations in muscle (72 +/- 16%) and adipose tissue (69 +/- 9%) than in plasma (42 +/- 3%) (P < 0.05). We conclude that hypoglycemia increases the generation of norepinephrine and gluconeogenic substrates in key target tissues, while increasing the plasma-tissue concentration gradient for glucose. These changes suggest the stimulation of glucose extraction by peripheral tissues, despite systemic counterregulatory hormone release and local sympathetic activation.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Borsheim, H. Kobayashi, D. L. Traber, and R. R. Wolfe Compartmental distribution of amino acids during hemodialysis-induced hypoaminoacidemia Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E643 - E652. [Abstract] [Full Text] [PDF]

				V. Qvisth, E. Hagstrom-Toft, S. Enoksson, E. Moberg, P. Arner, and J. Bolinder Human Skeletal Muscle Lipolysis Is More Responsive to Epinephrine Than to Norepinephrine Stimulation in Vivo J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 665 - 670. [Abstract] [Full Text] [PDF]

				N. N. Zammitt and B. M. Frier Hypoglycemia in Type 2 Diabetes: Pathophysiology, frequency, and effects of different treatment modalities Diabetes Care, December 1, 2005; 28(12): 2948 - 2961. [Full Text] [PDF]

				C. Meyer, P. Saar, N. Soydan, M. Eckhard, R. G. Bretzel, J. Gerich, and T. Linn A Potential Important Role of Skeletal Muscle in Human Counterregulation of Hypoglycemia J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6244 - 6250. [Abstract] [Full Text] [PDF]

				L. C. C. Navegantes, N. M. Z. Resano, A. M. Baviera, R. H. Migliorini, and I. C. Kettelhut Effect of sympathetic denervation on the rate of protein synthesis in rat skeletal muscle Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E642 - E647. [Abstract] [Full Text] [PDF]

				V. Stich, T. Pelikanova, P. Wohl, C. Sengenes, A. Zakaroff-Girard, M. Lafontan, and M. Berlan Activation of {alpha}2-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E599 - E607. [Abstract] [Full Text] [PDF]

				S. Enoksson, S. K. Caprio, F. Rife, G. I. Shulman, W. V. Tamborlane, and R. S. Sherwin Defective Activation of Skeletal Muscle and Adipose Tissue Lipolysis in Type 1 Diabetes Mellitus during Hypoglycemia J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1503 - 1511. [Abstract] [Full Text] [PDF]

				R. Amin, K. Ross, C. L. Acerini, J. A. Edge, J. Warner, and D. B. Dunger Hypoglycemia Prevalence in Prepubertal Children With Type 1 Diabetes on Standard Insulin Regimen: Use of Continuous Glucose Monitoring System Diabetes Care, March 1, 2003; 26(3): 662 - 667. [Abstract] [Full Text] [PDF]

				T. P. Monsod, D. E. Flanagan, F. Rife, R. Saenz, S. Caprio, R. S. Sherwin, and W. V. Tamborlane Do Sensor Glucose Levels Accurately Predict Plasma Glucose Concentrations During Hypoglycemia and Hyperinsulinemia? Diabetes Care, May 1, 2002; 25(5): 889 - 893. [Abstract] [Full Text] [PDF]

				R. P. Hoffman, C. A. Sinkey, J. M. Dopp, and B. G. Phillips Systemic and Local Adrenergic Regulation of Muscle Glucose Utilization During Hypoglycemia in Healthy Subjects Diabetes, March 1, 2002; 51(3): 734 - 742. [Abstract] [Full Text] [PDF]

				F. A. M. Baumeister, B. Rolinski, R. Busch, and P. Emmrich Glucose Monitoring With Long-Term Subcutaneous Microdialysis in Neonates Pediatrics, November 1, 2001; 108(5): 1187 - 1192. [Abstract] [Full Text] [PDF]

				E. Cersosimo, P. Garlick, and J. Ferretti Abnormal Glucose Handling by the Kidney in Response to Hypoglycemia in Type 1 Diabetes Diabetes, September 1, 2001; 50(9): 2087 - 2093. [Abstract] [Full Text] [PDF]

				B. Stallknecht, J. J. Larsen, K. J. Mikines, L. Simonsen, J. Bulow, and H. Galbo Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue Am J Physiol Endocrinol Metab, August 1, 2000; 279(2): E376 - E385. [Abstract] [Full Text] [PDF]

				V. Stich, I. de Glisezinski, M. Berlan, J. Bulow, J. Galitzky, I. Harant, H. Suljkovicova, M. Lafontan, D. Riviere, and F. Crampes Adipose tissue lipolysis is increased during a repeated bout of aerobic exercise J Appl Physiol, April 1, 2000; 88(4): 1277 - 1283. [Abstract] [Full Text] [PDF]

				T. W. Lameris, A. H. van den Meiracker, F. Boomsma, G. Alberts, S. de Zeeuw, D. J. Duncker, P. D. Verdouw, and A. J. M. I.'t Veld Catecholamine handling in the porcine heart: a microdialysis approach Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1562 - H1569. [Abstract] [Full Text] [PDF]

				K. Zierler Whole body glucose metabolism Am J Physiol Endocrinol Metab, March 1, 1999; 276(3): E409 - E426. [Abstract] [Full Text] [PDF]

				L. Schaupp, M. Ellmerer, G. A. Brunner, A. Wutte, G. Sendlhofer, Z. Trajanoski, F. Skrabal, T. R. Pieber, and P. Wach Direct access to interstitial fluid in adipose tissue in humans by use of open-flow microperfusion Am J Physiol Endocrinol Metab, February 1, 1999; 276(2): E401 - E408. [Abstract] [Full Text] [PDF]

				M. Ellmerer, L. Schaupp, G. Sendlhofer, A. Wutte, G. A. Brunner, Z. Trajanoski, F. Skrabal, P. Wach, and T. R. Pieber Lactate Metabolism of Subcutaneous Adipose Tissue Studied by Open Flow Microperfusion J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4394 - 4401. [Abstract] [Full Text]

				T. W. Jones, P. Porter, R. S. Sherwin, E. A. Davis, P. O'Leary, F. Frazer, G. Byrne, S. Stick, and W. V. Tamborlane Decreased Epinephrine Responses to Hypoglycemia during Sleep N. Engl. J. Med., June 4, 1998; 338(23): 1657 - 1662. [Abstract] [Full Text] [PDF]