AJP - Endocrinology and Metabolism, Vol 270, Issue 2 E251-E258, Copyright © 1996 by American Physiological Society

ARTICLES

Effects of prolonged glucose infusion on insulin secretion, clearance, and action in normal subjects

G. Boden, J. Ruiz, C. J. Kim and X. Chen
Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.

It was the aim of this study to determine whether prolonged hyperglycemia can produce "glucose toxicity" in normal human subjects. To this end, plasma glucose was clamped at approximately 5, approximately 8.8, and approximately 12.6 mM for 68 h in healthy volunteers. Rates of insulin secretion (by deconvolution of plasma C-peptide) and rates of insulin clearance [area under curve (AUC) 24 h insulin secretion/AUC 24 h insulin] were determined. Pre- and posthyperglycemia glucose turnover was measured (with [6,6-2H2]glucose) during euglycemic-hyperinsulinemic clamping to assess peripheral (muscle) and hepatic insulin action. Hyperglycemia (approximately 12.6 mM) for 68 h was associated with significant reductions in rates of insulin secretion (-35%, P < 0.05), insulin clearance (-57%, P < 0.05), glucose infusion rates needed to maintain hyperglycemia (-36%, P < 0.05), and insulin-stimulated glucose uptake (-55%, P < 0.01). No significant changes were seen during approximately 8.8 mM hyperglycemia or during euglycemia. These data showed that 12.6 mM hyperglycemia, but not 8.8 mM hyperglycemia or euglycemia, was associated with reduced insulin secretion, insulin clearance, and peripheral (muscle) insulin action. We concluded that 1) in normal subjects, desensitization to glucose involving beta-cells and muscle developed at plasma glucose concentrations between approximately 9 and approximately 12 mM, and 2) these effects were partially compensated for by a decrease in insulin clearance.

This article has been cited by other articles:

				J. L. Evans, I. D. Goldfine, B. A. Maddux, and G. M. Grodsky Are Oxidative Stress-Activated Signaling Pathways Mediators of Insulin Resistance and {beta}-Cell Dysfunction? Diabetes, January 1, 2003; 52(1): 1 - 8. [Abstract] [Full Text] [PDF]

				S. Lemosquet, E. Debras, M. Balage, J. F. Hocquette, H. Rulquin, and J. Grizard Short-term mild hyperglycemia enhances insulin-stimulated glucose disposal in lactating goats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R464 - R474. [Abstract] [Full Text] [PDF]

				L. L. Kjems, B. M. Kirby, E. M. Welsh, J. D. Veldhuis, M. Straume, S. S. McIntyre, D. Yang, P. Lefebvre, and P. C. Butler Decrease in {beta}-Cell Mass Leads to Impaired Pulsatile Insulin Secretion, Reduced Postprandial Hepatic Insulin Clearance, and Relative Hyperglucagonemia in the Minipig Diabetes, September 1, 2001; 50(9): 2001 - 2012. [Abstract] [Full Text] [PDF]

				D. B. Pawlak, J. M. Bryson, G. S. Denyer, and J. C. Brand-Miller High Glycemic Index Starch Promotes Hypersecretion of Insulin and Higher Body Fat in Rats without Affecting Insulin Sensitivity J. Nutr., January 1, 2001; 131(1): 99 - 104. [Abstract] [Full Text]

				C. E. Gleason, M. Gonzalez, J. S. Harmon, and R. P. Robertson Determinants of glucose toxicity and its reversibility in the pancreatic islet beta -cell line, HIT-T15 Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E997 - E1002. [Abstract] [Full Text] [PDF]

				D. R. Laybutt, C. Schmitz-Peiffer, A. K. Saha, N. B. Ruderman, T. J. Biden, and E. W. Kraegen Muscle lipid accumulation and protein kinase C activation in the insulin-resistant chronically glucose-infused rat Am J Physiol Endocrinol Metab, December 1, 1999; 277(6): E1070 - E1076. [Abstract] [Full Text] [PDF]

				P. Maechler, E. D. Kennedy, H. Wang, and C. B. Wollheim Desensitization of Mitochondrial Ca2+ and Insulin Secretion Responses in the Beta Cell J. Biol. Chem., August 14, 1998; 273(33): 20770 - 20778. [Abstract] [Full Text] [PDF]