AJP - Endocrinology and Metabolism, Vol 268, Issue 3 E410-E421, Copyright © 1995 by American Physiological Society

ARTICLES

Insulinopenia and hyperglycemia influence the in vivo partitioning of GE and SI

M. J. Christopher, C. Rantzau, G. M. Ward and F. P. Alford
Department of Endocrinology, St. Vincent's Hospital, Fitzroy, Victoria, Australia.

We determined the impact of variable insulinemia and glycemia on the in vivo partitioning of glucose effectiveness (GE) and insulin sensitivity (SI) and the in vitro intracellular processing of glucose metabolism. Six somatostatin- and [3-3H]glucose-infused dogs underwent euglycemic and hyperglycemic clamps at four physiological insulin (Ins) levels before a muscle biopsy. From the rates of glucose infusion (GINF), total glucose disposal (Rd), total glycolysis (GF), and glucose storage (GS), plots of delta GINF, delta Rd, delta GS vs. delta log Ins concentration were found to be linear for each dog, allowing calculation of the partitioning of GE and SI into their major in vivo sites (periphery vs. liver) and intracellular metabolic pathways (GS vs. GF). Insulinopenia induced a significant reduction in total GE. From insulinopenia to high insulinemia, the 2.3-fold increase in total GE was due to the increased peripheral glucose responsiveness of the GS pathway. Hyperglycemia induced a significant reduction in total SI, with approximately one-half of this reduction due to the decreased peripheral insulin responsiveness of the GF pathway. In skeletal muscle, both glycogen content and glycogen synthase fractional activity were positively correlated with log Ins concentration, Rd, and GS but negatively correlated with glucose 6-phosphate concentration. Moreover, both Rd and GS were negatively correlated with lactate concentration. We conclude that 1) the inhibition of GE and SI induced by insulinopenia and hyperglycemia, respectively, is due mainly to the reduced peripheral responsiveness of contrasting intracellular metabolic pathways; and 2) hyperinsulinemia and/or hyperglycemia stimulates glycogen synthesis and GF but not nonoxidative glycolysis.

This article has been cited by other articles:

				M. Christopher, C. Rantzau, Z.-P. Chen, R. Snow, B. Kemp, and F. P. Alford Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E1131 - E1140. [Abstract] [Full Text] [PDF]

				M. J. Christopher, C. Rantzau, G. McConell, B. E. Kemp, and F. P. Alford Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs J Appl Physiol, March 1, 2005; 98(3): 930 - 939. [Abstract] [Full Text] [PDF]

				M. J. Christopher, Z.-P. Chen, C. Rantzau, B. E. Kemp, and F. P. Alford Skeletal muscle basal AMP-activated protein kinase activity is chronically elevated in alloxan-diabetic dogs: impact of exercise J Appl Physiol, October 1, 2003; 95(4): 1523 - 1530. [Abstract] [Full Text] [PDF]

				G. Pacini, K. Thomaseth, and B. Ahren Contribution to glucose tolerance of insulin-independent vs. insulin-dependent mechanisms in mice Am J Physiol Endocrinol Metab, October 1, 2001; 281(4): E693 - E703. [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]

				R. Hovorka, F. Shojaee-Moradie, P. V. Carroll, L. J. Chassin, I. J. Gowrie, N. C. Jackson, R. S. Tudor, A. M. Umpleby, and R. H. Jones Partitioning glucose distribution/transport, disposal, and endogenous production during IVGTT Am J Physiol Endocrinol Metab, May 1, 2002; 282(5): E992 - E1007. [Abstract] [Full Text] [PDF]