It is known that various hormones influence the process of urine formation; and especially hormones elaborated by hypophysis and adrenal cortex have powerful renotropic action. But the relation between insulin and urine formation has not been adequately explored.
Measurements of electrical potentials in the proximal and distal nephrons of the rats and amphibian necturus strongly suggest that sodium is actively reabsorbed from glomerular filtrate (Solomon, 1957; Windhager, 1959; Giebish, 1961). Sodium
ion moves from the tubular lumen, across the peritubular cell membrane, and into the interstitium against electrochemical gradient. Now, it is widely assumed that transport of sodium ion is the primary event in the reabsorption of the bulk of the glomerular filtrate. It would, therefore, be reasonable that the active transport of sodium is the reabsorptive process which requires high energy and oxygen. In the intact kidney, an association between sodium transport and respiration is observed
by Lassen(1961) and he suggested that renal oxygen consumption is increased as a function of sodium reabsorption increased. But the evidence for active ion transport at the expense of anaerobic metabolism is scarce, and little is known about the metabolic pathway involved in such ion movement.
It is well known evidence that insulin, produced by the beta cell of the islet of Langerhans in the pancreas, promotes a reduction in the blood sugar by the actions of whether it increase the glucokinase activity(Cori, 1945) or change the cellular membrane permeability(Levin et al, 1950; Goldstein et al, 1953). In view of the fact that the renal tubular function is affected by both membrane permeability change and oxidative metabolism, it is expected that there might be some close relationship between insulin and renal function. This investigation is undertaken to study the action of insuli on the process of urine formation.
Materials and Methods
42 female dogs weighing around 10kg were used for the experiment. Under pentobarbital anesthesia tracheal tube was placed during the experiment. Blood sampling and drug infusion were performed through the cannula inserted into femoral artery and vein. Urine samples were taken through Foley catheter in the urethra. The drug infusion was given one hour after the operative procedure to avoid the influence of operation perse.
Infusing solution consisted of 0.9 per cent saline containing testing agents, and 2.0 M urea was added to induce diuresis. Inulin infusion was given in rate of 1 mg per minute per kg of animal weight and para-aminohippuric acid 2.0 mg per minute
per kg of animal weight after priming dose of 50 mg of inulin per kg and 120 mg of para-aminohippuric acid per kg respectively. After the rate of urinary flow stabilized constant sampling of urine and blood was taken at same time as well as the measurement of blood pressure.
Chemical determinations were performed with the methods of Shreiner(1950) for inulin, of Smith modification(1945) for PAH, of flame photometer for electrolytes, and Folin-Wu method modified by Nelson(1944) for blood sugar.
1. Injection of insulin 8 units, produced gradual decrease of blood sugar level and marked decrease of Tm^^PAH. But inulin clearance and renal plasma flow were not affected, indicating no influence on the rate of renal filtration and renal blood flow.
2. Urinary flow increased reciprocally to the decrease of blood sugar. This phenomenon appears to be related with reabsorption of sodium through renal tubules, namely the rate of sodium reabsorption decreased in contrast to the increase of total sodium output(excretion) resulting into marked increase of osmolar clearance. Serum concentration of sodium was not influenced by insulin, but potassium concentration decreased.
3. Administration of alloxan 150 mg/kg brought transient reduction of blood sugar level followed by the increase to double concentration at one hour after the injection, and this level was maintained thereafter. Inulin clearance was not altered, but urine flow increased slightly. Sodium output gradually decreased
following transient increase corresponding to initial hypoglycemic phase. the amount of reabsorbed sodium through renal tubules increased in proportion to the elevation of blood sugar level.
4. Injection of 25 mg/kg of chlorpropamide, which is known to stimulate insulin production from pancreas indirectly, induced mild reduction of blood sugar level, accompanied by increase of urine flow and urinary output of sodium. But this effect was lesser than in case of insulin.
5. Injection of 10 mg/kg of phenformin, which is known to reduce the blood sugar through acceleration of peripheral sugar consumption without influencing the pancreas, did not change the urinary flow and sodium output, and the reduction of blood sugar was rather mild.
6. By addition of 0.02T potassium chloride to the infusate following the injection of insulin, 8 units/kg, the inhibition of sodium reabsorption was markedly alleviated and consequently urinary flow did not increase as much as insulin administration alone, in spite of marked decrease of blood sugar level.
7. The data obtained in present experiments indicate that increase of urinary flow and inhibition of sodium reabsorption following the administration of insulin is mediated through reduction of blood sugar level and plasma potassium concentration.