ROLE OF THE KIDNEY IN PLASMA-GLUCOSE REGULATION DURING HYPERGLYCEMIA

Little is known about the role of the kidney in plasma glucose regulat ion during hyperglycemia. We studied 12 overnight-fasted conscious dog s after either intrarenal (IR, n = 6) or peripheral (PH, n = 6) dextro se infusion to maintain hyperglycemia without glycosuria. Systemic and renal glucose kinetics were measured with [6-H-3]glucose, lactate bal ance was measured by arteriovenous difference, and glycogen content wa s assayed in the kidneys. Plasma glucose (similar to 5.5 vs. similar t o 6.3 mM), insulin (similar to 70 vs. similar to 110 pM), and glucose appearance (similar to 14 vs. similar to 16 mu mol.kg(-1).min(-1)) inc reased comparably in both groups (P < 0.05). In IR, fractional extract ion of glucose (FEGlc) increased from 4.1 +/- 0.2 to 16.1 +/- 0.5% (P < 0.001) and lactate balance reversed to renal output (+1.3 +/- 0.2 vs . -0.9 +/- 0.2 mu mol.kg(-1).min(-1), P < 0.01). Glycogen content was twofold higher in the left (127 +/- 33 mu g/g tissue) than in the righ t kidney (56 +/- 11 mu g/g tissue, P < 0.01). In PH, FEGlc decreased f rom 4.9 +/- 0.6 to 2.2 +/- 0.3% (P < 0.05), renal glucose utilization did not change (similar to 1.3 mu mol.kg(-1).min(-1)), and glycogen co ntent was equal in both kidneys (similar to 45 mu g/g tissue). We conc lude that, although the kidney plays a minor role in plasma glucose di sposal in physiological hyperglycemia, increased glucose uptake, glyco gen storage, and lactate formation precede glycosuria and may represen t important mechanisms by which the kidney contributes to normalizatio n of plasma glucose in diabetes.