Diabetes, Vol 36, Issue 3 382-389, Copyright © 1987 by American Diabetes Association

ARTICLES

Similar dose responsiveness of hepatic glycogenolysis and gluconeogenesis to glucagon in vivo

RW Stevenson, KE Steiner, MA Davis, GK Hendrick, PE Williams, WW Lacy, L Brown, P Donahue, DB Lacy and AD Cherrington

This study was undertaken to determine whether the dose-dependent effect of glucagon on gluconeogenesis parallels its effect on hepatic glycogenolysis in conscious overnight-fasted dogs. Endogenous insulin and glucagon secretion were inhibited by somatostatin (0.8 micrograms X kg-1 X min-1), and intraportal replacement infusions of insulin (213 +/- 28 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1) were given to maintain basal hormone concentrations for 2 h (12 +/- 2 microU/ml and 108 +/- 23 pg/ml, respectively). The glucagon infusion was then increased 2-, 4-, 8-, or 12-fold for 3 h, whereas the rate of insulin infusion was left unchanged. Glucose production (GP) was determined with 3-[3H]glucose, and gluconeogenesis (GNG) was assessed with tracer (U-[14C]alanine conversion to [14C]glucose) and arteriovenous difference (hepatic fractional extraction of alanine, FEA) techniques. Increases in plasma glucagon of 53 +/- 8, 199 +/- 48, 402 +/- 28, and 697 +/- 149 pg/ml resulted in initial (15-30 min) increases in GP of 1.1 +/- 0.4 (N = 4), 4.9 +/- 0.5 (N = 4), 6.5 +/- 0.6 (N = 6), and 7.7 +/- 1.4 (N = 4) mg X kg-1 X min-1, respectively; increases in GNG (approximately 3 h) of 48 +/- 19, 151 +/- 50, 161 +/- 25, and 157 +/- 7%, respectively; and increases in FEA (3 h) of 0.14 +/- 0.07, 0.37 +/- 0.05, 0.42 +/- 0.04, and 0.40 +/- 0.17, respectively. In conclusion, GNG and glycogenolysis were similarly sensitive to stimulation by glucagon in vivo, and the dose-response curves were markedly parallel.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. E. Dunning and J. E. Gerich The Role of {alpha}-Cell Dysregulation in Fasting and Postprandial Hyperglycemia in Type 2 Diabetes and Therapeutic Implications Endocr. Rev., May 1, 2007; 28(3): 253 - 283. [Abstract] [Full Text] [PDF]

				S.-S. Chen, Y. Zhang, T. S. Santomango, P. E. Williams, D. B. Lacy, and O. P. McGuinness Glucagon chronically impairs hepatic and muscle glucose disposal Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E928 - E935. [Abstract] [Full Text] [PDF]

				C. Everett-Grueter, D. S. Edgerton, E. P. Donahue, S. Vaughan, C. A. Chu, D. K. Sindelar, and A. D. Cherrington The effect of an acute elevation of NEFA concentrations on glucagon-stimulated hepatic glucose output Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E449 - E459. [Abstract] [Full Text] [PDF]

				S.-S. Chen, C. J. Torres-Sanchez, N. Hosein, Y. Zhang, D. B. Lacy, and O. P. McGuinness Time course of the hepatic adaptation to TPN: interaction with glycogen depletion Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E163 - E170. [Abstract] [Full Text] [PDF]

				S. M. Gustavson, C. A. Chu, M. Nishizawa, B. Farmer, D. Neal, Y. Yang, S. Vaughan, E. P. Donahue, P. Flakoll, and A. D. Cherrington Glucagon's actions are modified by the combination of epinephrine and gluconeogenic precursor infusion Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E534 - E544. [Abstract] [Full Text] [PDF]

				S. M. Gustavson, C. A. Chu, M. Nishizawa, B. Farmer, D. Neal, Y. Yang, E. P. Donahue, P. Flakoll, and A. D. Cherrington Interaction of glucagon and epinephrine in the control of hepatic glucose production in the conscious dog Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E695 - E707. [Abstract] [Full Text] [PDF]

				R. E. Goldstein, L. Rossetti, B. A. J. Palmer, R. Liu, D. Massillon, M. Scott, D. Neal, P. Williams, B. Peeler, and A. D. Cherrington Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E946 - E957. [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]

				C. A. Chu, D. K. Sindelar, D. W. Neal, E. J. Allen, E. P. Donahue, and A. D. Cherrington Effect of a selective rise in sinusoidal norepinephrine on HGP is due to an increase in glycogenolysis Am J Physiol Endocrinol Metab, January 1, 1998; 274(1): E162 - E171. [Abstract] [Full Text] [PDF]

				M. Shiota, P. A. Jackson, H. Bischoff, M. McCaleb, M. Scott, M. Monohan, D. W. Neal, and A. D. Cherrington Inhibition of glycogenolysis enhances gluconeogenic precursor uptake by the liver of conscious dogs Am J Physiol Endocrinol Metab, November 1, 1997; 273(5): E868 - E879. [Abstract] [Full Text] [PDF]

				O. P. McGuinness, V. Shau, E. M. Benson, M. Lewis, R. T. Snowden, J. E. Greene, D. W. Neal, and A. D. Cherrington Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog Am J Physiol Endocrinol Metab, October 1, 1997; 273(4): E674 - E681. [Abstract] [Full Text] [PDF]