Effects of physiologic hyperinsulinemia on systemic, renal and hepatic glucose, glutamine and free fatty acid metabolism. Meyer, Christian, Jean Dostou, Veena Nadkarni and John Gerich,. University of Rochester School of Medicine, Departments of Medicine1 and Physiology and Pharmacology2, Rochester, New York
APStracts 5:0149F, 1998.
To assess the effect of physiologic hyperinsulinemia on renal and hepatic substrate metabolism, we assessed systemic and renal glucose release (and uptake), systemic and renal gluconeogenesis from glutamine, and certain aspects of systemic and renal glutamine and free fatty acid (FFA) metabolism under basal postabsorptive conditions and during 4 hour hyperinsulinemic euglycemic clamp experiments in nine normal volunteers using a combination of isotopic techniques and renal balance measurements. Hepatic glucose release and glutamine gluconeogenesis were calculated as the difference between systemic and renal measurements. Infusion of insulin suppressed systemic glucose release and glutamine gluconeogenesis approximately 50% during the last hour of the insulin infusion, p < 0.001. Renal glucose release and glutamine gluconeogenesis decreased from 2.3 +/- 0.4 to 0.9 +/- 0.2 (p < 0.002) and from 0.52 +/- 0.07 to 0.14 +/- 0.03 _molkg-1min-1 (p < 0.001), respectively. Hepatic glucose release and glutamine gluconeogenesis decreased from 8.7 +/- 0.4 to 4.5 +/- 0.5 (p < 0.001) and from 0.35 +/- 0.02 to 0.27 +/- 0.03 _molkg-1min-1 (p < 0.002), respectively. Renal glucose uptake increased from 1.61 +/- 0.19 to 2.18 +/- 0.25 _molkg-1min-1 (p = 0.029), but accounted for only about 5% of systemic glucose disposal (40.6 +/- 4.3 _mol_kg-1_min-1). Both systemic and renal FFA clearance increased approximately four-fold (both p < 0.001). Nevertheless, renal FFA uptake decreased (p = 0.024) and was inversely correlated with renal glucose uptake (r = -0.582, p = 0.011). Finally, insulin increased systemic glutamine release (p = 0.007), uptake (p < 0.005) and clearance (p < 0.001) while not affecting renal glutamine uptake and release (both p > 0.4). 

Received 24 April 1998; accepted in final form 20 August 1998.
APS Manuscript Number F92-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998