The effects of glucose and insulin on renal electrolyte transport.

Abstract

A B S T R A C r The effects of hyperglycemia and hyperinsulinemia on renal handling of -sodium, calcium, and phosphate were studied in dogs employing the r.ecollection micropuncture technique. Subthreshold sustained hyperglycemia resulted in an isonatric inhibition of proximal tubular sodium, fluid, calcium, and phosphate reabsorption by 8-14%. Fractional excretion of sodium and phosphate, however, fell (P < 0.01) indicating that the increased delivery of these ions was reabsorbed in portions of the nephron distal to the site of puncture and in addition net sodium and phosphate transport was enhanced resulting in a significant antinatriuresis and antiphosphaturia.The creation of a steady state plateau of hyperinsulinemia while maintaining the blood glucose concentration at euglycemic levels mimicked the effects of hyperglycemia on proximal tubular transport and fractional excretion of sodium and calcium. Tubular fluid to plasma inulin ratio fell, similar to the hyperglycemic studies. These results suggest that the effects of hyperglycemia on renal handling of sodium and calcium may be mediated through changes in plasma insulin concentration. In contrast to hyperglycemia, however, hyperinsulinemia caused a significant fall in tubular fluid to plasma phosphate ratio with enhanced proximal tubular phosphate reabsorption (P < 0.02). This occurred concomitantly with a significant inhibition of proximal tubular sodium transport. These data indicate that insulin has a direct effect on proximal tubular phosphate reabsorption, and this effect of insulin is masked by the presence of increased amounts of unreabsorbed glucose in the tubule that ensues when hyperinsulinemia occurs -secondary to hyperglycemia. Fractional excretion Dr. Agus is a Clinical Investigator of the Veteran's Administration.

Natriuresis of Fasting in Intact and Adrenalectomized Rats

“…In addition, diuretic and natriuretic effects of a physiologic dose of insulin (i.v.) were not observed in our clearance experiments with fasted intact rats (unpublished data), and such findings are compatible with reports in humans and dogs (9,10). Therefore, the apparent natriuretic effect of insulin in intact rats (Fig.…”

“…The antidiuretic effect of insulin (9,10) has been attributed to fasting-induced natriuresis and anti -natriuresis by subsequent glucose feeding. In a preliminary report from this laboratory it was confirmed that the negative balance of sodium in fasted rats was not improved but rather enhanced by the administration of insulin (11).…”

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice

“…Epidemiological studies indicate that insulin resistance and arterial hypertension are interrelated [35,36]. It has been suggested that the prohypertensive action of insulin could be due to increased sodium reabsorption by acting on distinct segments of the renal tubule [37][38][39]. A feedback mechanism limits insulininduced sodium retention when extracellular fluid volume is expanded [40], which is impaired in rats with hypertension associated with insulin resistance [41].…”

Increased insulin resistance in salt sensitive essential hypertension

“…26,27 It has been proposed that insulin resistance and hyperinsulinism may predispose the development of salt sensitive hypertension through an increase in renal sodium reabsorption. 3,28 Moreover, in response to high salt intake, salt sensitive hypertensives present alterations in both the sympathetic nervous and the renin-angiotensin systems 29 which may promote vasoconstriction and decreased muscle blood flow leading to insulin resistance. In this sense, Baron et al 30 demonstrated that insulin sensitivity is related to muscular blood flow increase induced by insulin itself.…”