RENAL LACTATE METABOLISM AND GLUCONEOGENESIS DURING INSULIN-INDUCED HYPOGLYCEMIA

The contribution of gluconeogenic precursors to renal glucose producti on (RGP) during insulin-induced hypoglycemia was assessed in conscious dogs. Ten days after surgical placement of sampling catheters in the right and left; renal veins and femoral artery and an infusion cathete r in the left renal artery, systemic and renal glucose and glycerol ki netics were measured with peripheral infusions of [6-H-3]glucose and [ 2-C-13]glycerol. Renal blood flow was determined with a flowprobe, and the renal balance of lactate, alanine, and glycerol was calculated by arteriovenous difference. After baseline, six dogs received 2-h simul taneous infusions of peripheral insulin (4 mU . kg(-1) . min(-1)) and left intrarenal [6,6-H-2]dextrose (14 mu mol . kg(-1) . min(-1)) to ac hieve and maintain left renal normoglycemia during systemic hypoglycem ia. Arterial glucose decreased from 5.3 +/- 0.1 to 2.2 +/- 0.1 mmol/l; insulin increased from 46 +/- 5 to 1,050 +/- 50 pmol/l; epinephrine, from 130 +/- 8 to 1,825 +/- 50 pg/ml; norepinephrine, from 129 +/- 6 t o 387 +/- 15 pg/ml; and glucagon, from 52 +/- 2 to 156 +/- 12 pg/ml ta ll P < 0.01). RGP increased from 1.7 +/- 0.4 to 3.0 +/- 0.5 (left) and from 0.6 +/- 0.2 to 3.2 +/- 0.2 (right) pmol kg-l min (P < 0.01). Who le-body glycerol appearance increased from 6.0 +/- 0.5 to 7.7 +/- 0.7 mu mol . kg(-1) . min(-1)(P < 0.01); renal conversion of glycerol to g lucose increased from 0.13 +/- 0.04 to 0.30 +/- 0.10 (left) and from 0 .11 +/- 0.03 to 0.25 +/- 0.05 (right) mu mol . kg(-1) . min(-1), (P <0 .05). Net renal gluconeogenic precursor uptake increased from 1.5 +/- 0.4 to 5.0 +/- 0.4 (left) and from 0.9 +/- 0.2 to 3.8 +/- 0.4 (right) mu mol . kg(-1) . min(-1) (P < 0.01). Renal lactate uptake could accou nt for similar to 40% of postabsorptive RGP and for 60% of RGP during hypoglycemia. These results indicate that gluconeogenic precursor extr action by the kidney, particularly lactate, is stimulated by counterre gulatory hormones and accounts for a significant fraction of the enhan ced gluconeogenesis induced by hypoglycemia.