Diabetes, Vol 45, Issue 10 1373-1378, Copyright © 1996 by American Diabetes Association

ARTICLES

Epinephrine exerts opposite effects on peripheral glucose disposal and glucose-stimulated insulin secretion. A stable label intravenous glucose tolerance test minimal model study

A Avogaro, G Toffolo, A Valerio and C Cobelli
Department of Clinical and Experimental Medicine, University of Padova, Italy.

Epinephrine (EPI) plays a pivotal role in regulating glucose metabolism both in splanchnic and peripheral tissues. Nevertheless, previous studies did not clarify the mechanisms by which EPI affect both glucose disposal processes in peripheral tissues and beta-cell secretion. The aim of this study was to investigate, in six normal volunteers, the effects of elevated EPI concentration on peripheral glucose disposal and insulin secretion by using the stable labeled (either [6,6-2H2] or [2-2H1]glucose) intravenous glucose tolerance test (IVGTT) in conjunction with the minimal models of labeled glucose disappearance and C-peptide secretion. Elevated plasma EPI concentration significantly decreased glucose effectiveness (SG*) by 29% (0.0059 +/- 0.0013 vs. 0.0083 +/- 0.0011 min-1, P < 0.05), and even more, 61%, insulin sensitivity (SI*); (22 +/- 6 x 10(4) vs. 54 +/- 20 x 10(4) min-1.pmol.l-1; P < 0.01). These findings are not due to an isotopic effect induced by an enhanced glycogen breakdown, because the [2-2H1]glucose tracer, which is not incorporated into glycogen, gave results similar to those of [6,6-2H2]glucose tracer. No differences were observed in first phase cell sensitivity, phi 1, in the EPI study (199 +/- 91 vs. 245 +/- 144 10(9), NS), but there was a significant increase in the second-phase cell sensitivity to glucose phi 2, (15.2 +/- 1.7 vs. 17.7 +/- 4.4 10(9).min-1, P < 0.05). In conclusion, EPI selectively impairs peripheral glucose metabolism because of its unique ability to simultaneously and independently decrease glucose effectiveness and insulin sensitivity. Furthermore, EPI enhances phi 2, the ratio between the C-peptide amount secreted during the second phase and the area under the curve of the glucose signal, indicating that the observed increase of C-peptide concentration is due not only to the augmented glucose signal but also to a specific EPI-mediated enhancement of beta-cell responsivity to glucose.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. A Greenberg, C. N Boozer, and A. Geliebter Coffee, diabetes, and weight control. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 682 - 693. [Abstract] [Full Text] [PDF]

				A. Brehm, K. Thomaseth, E. Bernroider, P. Nowotny, W. Waldhausl, G. Pacini, and M. Roden The Role of Endocrine Counterregulation for Estimating Insulin Sensitivity from Intravenous Glucose Tolerance Tests J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2272 - 2278. [Abstract] [Full Text] [PDF]

				P. Vicini, A. Avogaro, M. E. Spilker, A. Gallo, and C. Cobelli Epinephrine effects on insulin-glucose dynamics: the labeled IVGTT two-compartment minimal model approach Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E78 - E84. [Abstract] [Full Text] [PDF]

				F. S. L. Thong and T. E. Graham Caffeine-induced impairment of glucose tolerance is abolished by beta -adrenergic receptor blockade in humans J Appl Physiol, June 1, 2002; 92(6): 2347 - 2352. [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]

				G. Toffolo, E. Breda, M. K. Cavaghan, D. A. Ehrmann, K. S. Polonsky, and C. Cobelli Quantitative indexes of {beta}-cell function during graded up&down glucose infusion from C-peptide minimal models Am J Physiol Endocrinol Metab, January 1, 2001; 280(1): E2 - E10. [Abstract] [Full Text] [PDF]

				J. Walston, K. Silver, H. Hilfiker, R. E. Andersen, M. Seibert, B. Beamer, J. Roth, E. Poehlman, and A. R. Shuldiner Insulin Response to Glucose Is Lower in Individuals Homozygous for the Arg 64 Variant of the {beta}-3-Adrenergic Receptor J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4019 - 4022. [Abstract] [Full Text]

				C. Cobelli, A. Caumo, and M. Omenetto Minimal model SG overestimation and SI underestimation: improved accuracy by a Bayesian two-compartment model Am J Physiol Endocrinol Metab, September 1, 1999; 277(3): E481 - E488. [Abstract] [Full Text] [PDF]

				M. C. Lekas, S. J. Fisher, B. El-Bahrani, M. van Delangeryt, M. Vranic, and Z. Q. Shi Glucose uptake during centrally induced stress is insulin independent and enhanced by adrenergic blockade J Appl Physiol, August 1, 1999; 87(2): 722 - 731. [Abstract] [Full Text] [PDF]