The participation of the renal tubules to the metabolism of insulin.

The role of renal tubules was explored by two kinds of experiments: (1) inhibition of the tubular reabsorption of insulin by induced polyuria; (2) suppression of insulin filtration by ureter clamping; 1. Anaesthetized dogs maintained in normoglycaemia by glucose compensation were infused with crystalline and 125I-insulins. Polyuria was induced by: (1) saline-bicarbonate infusion; (2) furosemide with saline-bicarbonate infusion to replace urine losses; (3) massive infusion of mannitol. Inulin and paraminohippuric acid were used to estimate the glomerular filtration rate and the renal plasma flow. The permeability of the glomerular wall (pore radius and total area of the pores per unit of path length) was determined by measuring the sieving curve of 131I-polyvinyl-pyrrolidone fractions during basal and treatment periods. Mannitol infusion was able to bring the insulin/inulin clearance ratio up the values of the sieving coefficient of insulin (insulin filtration rate) without modifying the permeability of the glomerular wall; saline infusion displayed a similar effect; furosemide, only a minute one although it induced a more marked polyuria. 2. Clamping of the left ureter was performed on dogs with catheters inserted into the artery, the left renal vein, the pelvis and a renal lymphatic vessel. Almost complete suppression of the glomerular filtration was achieved. It slightly increased the high insulinic concentration of the renal lymph, entailed a 1/3 decrease in the extraction ratio of insulin and reduced by half its renal clearance. In conclusion, the tubules participate to the catabolism of insulin by two different mechanisms: (1) an uptake from the tubular fluid which can be inhibited by diuretics exerting their main action on the proximal tubules; (2) a direct catabolism from the interstitial fluid resulting from the large permeability of the peritubular capillaries to insulin.