Effects of physiological hyperinsulinemia on systemic, renal, and hepatic substrate metabolism

To determine the effect of physiological hyperinsulinemia on renal and hepa tic substrate metabolism, we assessed systemic and renal glucose release an d uptake, systemic and renal gluconeogenesis from glutamine, and certain as pects of systemic and renal glutamine and free fatty acid (FFA) metabolism. These were assessed under basal postabsorptive conditions and during 4-h h yperinsulinemic euglycemic clamp experiments in nine normal volunteers usin g a combination of isotopic techniques and renal balance measurements. Hepa tic glucose release (HGR) and glutamine gluconeogenesis were calculated as the difference between systemic and renal measurements. Infusion of insulin suppressed systemic glucose release and glutamine gluconeogenesis by simil ar to 50% during the last hour of the insulin infusion (P < 0.001). Renal g lucose 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 mu mol.kg(- 1).min(-1) (P < 0.001), respectively. HGR and glutamine gluconeogenesis dec reased from 8.7 +/- 0.4 to 4.5 +/- 0.5 (P < 0.001) and from 0.35 +/- 0.02 t o 0.27 +/- 0.03 mu mol.kg(-1).min(-1) (P < 0.002), respectively. Renal gluc ose uptake (RGU) increased from 1.61 +/- 0.19 to 2.18 +/- 0.25 mu mol.kg(-1 ).min(-1) (P = 0.029) but accounted for only similar to 5% of systemic gluc ose disposal (40.6 +/- 4.3 mu mol. kg(-1).min(-1)). Both systemic and renal FFA clearance increased approximately fourfold (P < 0.001 for both). Never theless, renal FFA uptake decreased (P = 0.024) and was inversely correlate d with RGU (r = -0.582, P = 0.011). Finally, insulin increased systemic glu tamine release (P = 0.007), uptake (P < 0.005), and clearance (P < 0.001) b ut left renal glutamine uptake and release unaffected (P > 0.4 for both).