| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
AJP - Endocrinology and Metabolism, Vol 258, Issue 6 E1020-E1032, Copyright © 1990 by American Physiological Society
ARTICLES |
M. Ader and R. N. Bergman
Department of Physiology and Biophysics, University of Southern California, Los Angeles 90033.
Insulin may suppress hepatic glucose production directly, or indirectly via suppression of release of gluconeogenic substrates from extrasplanchnic tissues. To compare these mechanisms, we performed insulin dose-response experiments in conscious dogs at euglycemia, during somatostatin infusion, and intraportal glucagon replacement. Insulin was sequentially infused either intraportally (0.05, 0.20, 0.40, 1.0, 1.4, and/or 3.0; protocol I) or systemically at half the intraportal rate (0.025, 0.10, 0.20, 0.50, 0.70, and/or 1.5 mU.min-1.kg-1; protocol II). Exogenous glucose infused during clamps was labeled with 3-[3H]glucose (2 microCi/g) to prevent a fall in plasma specific activity (P greater than 0.2) that may have contributed to previous underestimations of hepatic glucose output (HGO). Portal insulins were up to threefold higher during intraportal infusion, but peripheral insulin levels were not different between the intraportal and systemic protocols [7 +/- 5 vs. 9 +/- 1, 12 +/- 4 vs. 13 +/- 6, 16 +/- 3 vs. 27 +/- 5, 70 +/- 23 vs. 48 +/- 8, 83 +/- 3 vs. 86 +/- 21, and 128 vs. 120 +/- 14 microU/ml for paired insulin doses; P greater than 0.06 by analysis of variance (ANOVA)]. Despite higher portal insulin levels in protocol I, HGO suppression was equivalent in the two protocols when systemic insulin was matched, from 3.3 +/- 0.1 to near-total suppression at 0.3 mg.min-1.kg-1 at the highest insulin infusion rate (3.0 mU.min-1.kg-1; P less than 0.0001) with intraportal insulin, from 2.9 +/- 0.8 to -0.8 +/- 0.2 mg.min-1.kg-1 in protocol II (P less than 0.001). Suppression of HGO was similar at matched systemic insulin, regardless of portal insulin, suggesting the primacy of insulin's action on the periphery in its restraint of hepatic glucose production.
This article has been cited by other articles:
|
|
 |
|
  E. Rother, A. C. Konner, and J. C. Bruning Neurocircuits integrating hormone and nutrient signaling in control of glucose metabolism Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E810 - E816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yoshii, T. K. T. Lam, N. Gupta, T. Goh, C. A. Haber, H. Uchino, T. T. Y. Kim, V. Z. Chong, K. Shah, I. G. Fantus, et al. Effects of portal free fatty acid elevation on insulin clearance and hepatic glucose flux Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1089 - E1097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Krudys, M. G. Dodds, S. M. Nissen, and P. Vicini Integrated model of hepatic and peripheral glucose regulation for estimation of endogenous glucose production during the hot IVGTT Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E1038 - E1046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Caumo and L. Luzi First-phase insulin secretion: does it exist in real life? Considerations on shape and function Am J Physiol Endocrinol Metab, September 1, 2004; 287(3): E371 - E385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Buettner, I. Ottinger, J. Scholmerich, and L. C. Bollheimer Preserved direct hepatic insulin action in rats with diet-induced hepatic steatosis Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E828 - E833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Gresl, R. J. Colman, T. C. Havighurst, L. O. Byerley, D. B. Allison, D. A. Schoeller, and J. W. Kemnitz Insulin sensitivity and glucose effectiveness from three minimal models: effects of energy restriction and body fat in adult male rhesus monkeys Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2003; 285(6): R1340 - R1354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Gupta, H. Sandhu, T. Goh, K. Shah, S. R. Wiesenthal, H. Yoshii, V. Chong, T. K. T. Lam, C. A. Haber, W. Williams, et al. Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E1002 - E1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Gabriely, X. H. Ma, X. M. Yang, G. Atzmon, M. W. Rajala, A. H. Berg, P. Scherer, L. Rossetti, and N. Barzilai Removal of Visceral Fat Prevents Insulin Resistance and Glucose Intolerance of Aging: An Adipokine-Mediated Process? Diabetes, October 1, 2002; 51(10): 2951 - 2958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Satake, M. C. Moore, K. Igawa, M. Converse, B. Farmer, D. W. Neal, and A. D. Cherrington Direct and Indirect Effects of Insulin on Glucose Uptake and Storage by the Liver Diabetes, June 1, 2002; 51(6): 1663 - 1671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Mittelman, G. W. Van Citters, E. L. Kirkman, and R. N. Bergman Extreme Insulin Resistance of the Central Adipose Depot In Vivo Diabetes, March 1, 2002; 51(3): 755 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Edgerton, S. Cardin, M. Emshwiller, D. Neal, V. Chandramouli, W. C. Schumann, B. R. Landau, L. Rossetti, and A. D. Cherrington Small Increases in Insulin Inhibit Hepatic Glucose Production Solely Caused by an Effect on Glycogen Metabolism Diabetes, August 1, 2001; 50(8): 1872 - 1882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Gerich, C. Meyer, H. J. Woerle, and M. Stumvoll Renal Gluconeogenesis: Its importance in human glucose homeostasis Diabetes Care, February 1, 2001; 24(2): 382 - 391. [Abstract] [Full Text]
|
|
|
|
|
|
S. D. Mittelman and R. N. Bergman Inhibition of lipolysis causes suppression of endogenous glucose production independent of changes in insulin Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E630 - E637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Sindelar, K. Igawa, C. A. Chu, J. H. Balcom, D. W. Neal, and A. D. Cherrington Effect of a selective rise in hepatic artery insulin on hepatic glucose production in the conscious dog Am J Physiol Endocrinol Metab, April 1, 1999; 276(4): E806 - E813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Cersosimo, P. Garlick, and J. Ferretti Insulin regulation of renal glucose metabolism in humans Am J Physiol Endocrinol Metab, January 1, 1999; 276(1): E78 - E84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Meyer, J. Dostou, V. Nadkarni, and J. Gerich Effects of physiological hyperinsulinemia on systemic, renal, and hepatic substrate metabolism Am J Physiol Renal Physiol, December 1, 1998; 275(6): F915 - F921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Lewis, M. Vranic, and A. Giacca Role of free fatty acids and glucagon in the peripheral effect of insulin on glucose production in humans Am J Physiol Endocrinol Metab, July 1, 1998; 275(1): E177 - E186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pacini, G. Tonolo, M. Sambataro, M. Maioli, M. Ciccarese, E. Brocco, A. Avogaro, and R. Nosadini Insulin sensitivity and glucose effectiveness: minimal model analysis of regular and insulin-modified FSIGT Am J Physiol Endocrinol Metab, April 1, 1998; 274(4): E592 - E599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. McCall, S. R. Wiesenthal, Z. Q. Shi, K. Polonsky, and A. Giacca Insulin acutely suppresses glucose production by both peripheral and hepatic effects in normal dogs Am J Physiol Endocrinol Metab, February 1, 1998; 274(2): E346 - E356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Sindelar, C. A. Chu, D. W. Neal, and A. D. Cherrington Interaction of equal increments in arterial and portal vein insulin on hepatic glucose production in the dog Am J Physiol Endocrinol Metab, November 1, 1997; 273(5): E972 - E980. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
