The Effect of Insulin and of Anti-insulin Serum on Handling of Sodium by the Isolated, Perfused Kidney of the Streptozotocin-diabetic Rat

Abstract

We studied the effects of insulin and of anti-insulin serum (AIS) on sodium excretion in isolated diabetic and normal, fed, rat kidneys perfused at a constant pressure of 100 mm Hg with Krebs-Ringer bicarbonate buffer containing 7.5% bovine serum albumin and 5 mM glucose and gassed with 95% O2 and 5% CO2. The addition of insulin produced antinatriuresis in kidneys from diabetic rats but not in those from normal rats. Moreover, before the addition of insulin, the baseline rate of sodium excretion was greater in the diabetic rat kidney than in the normal rat kidney, while no differences in glomerular filtration rate (GFR) were observed. The addition of AIS (enough to bind 1.4 mU of insulin per milliliter of perfusate) produced a brisk natriuresis in kidneys from normal rats, and this natriuresis could be reversed by the addition of saturating amounts of insulin. By contrast, the addition of normal guinea pig serum to the perfusate of normal kidneys or AIS to the perfusate of diabetic kidneys was unassociated with natriuresis. We conclude that (a) insulin promoted antinatriuresis in diabetic but not in normal rat kidneys, (b) AIS promoted natriuresis in normal kidneys, and (c) this natriuresis was a specific effect of AIS and was reversed by the addition of insulin. Our data support the view that insulin-induced antinatriuresis depends on endogenous levels of circulating insulin and on the availability of insulin-binding sites in the kidney.

Insulin oedema

“…Sodium retention may also occur during insulin treatment of non-ketoacidotic diabetic patients, even in the absence of salt depletion (Saudek et al, 1974). Insulin has a direct sodium-retaining effect on the kidney in both man and experimental animals (De-Fronzo et al, 1975;Rostand et al, 1980), most marked in diabetic animals with preceding insulin deficiency and independent of changes in renal blood flow or the renin-aldosterone axis. Insulin oedema may thus be at least partly secondary to sodium retention resulting from a direct action of insulin on the renal tubule, and leading to an expansion of interstitial and plasma volumes.…”