Role of the kidney in plasma glucose regulation during hyperglycemia

Little is known about the role of the kidney in plasma glucose regulation during hyperglycemia. We studied 12 overnight-fasted conscious dogs after either intrarenal (IR, n = 6) or peripheral (PH, n = 6) dextrose infusion to maintain hyperglycemia without glycosuria. Systemic and renal glucose kinetics were measured with [6-H-3]glucose, lactate balance was measured by arteriovenous difference, and glycogen content was assayed in the kidneys. Plasma glucose (similar to 5.5 vs. similar to 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)) increased comparably in both groups (P < 0.05). In IR, fractional extraction 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 right kidney (56 +/- 11 mu g/g tissue, P < 0.01). In PH, FEGlc decreased from 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 content was equal in both kidneys (similar to 45 mu g/g tissue). We conclude that, although the kidney plays a minor role in plasma glucose disposal in physiological hyperglycemia, increased glucose uptake, glycogen storage, and lactate formation precede glycosuria and may represent important mechanisms by which the kidney contributes to normalization of plasma glucose in diabetes.