Effects of insulin and atrial natriuretic peptide on renal tubular sodium handling in sickle cell disease

Abstract

We assessed the effect of insulin and atrial natriuretic peptide (ANP) on renal sodium handling in eight patients with sickle cell disease (SCD), who are characterized by loss of vasa recta and long loops of Henle, and matched control subjects. During insulin infusion (50 mU. kg(-1). h(-1)), fractional sodium excretion decreased by 0.44 +/- 0.72% (P = 0.13) in patients with SCD and by 0. 57 +/- 0.34% (P = 0.002) in control subjects, whereas fractional distal sodium reabsorption increased by 4.1 +/- 1.5% (P < 0.001) and 3.0 +/- 1.5% (P < 0.001), respectively. Low-dose (0.3 pmol. kg(-1). h(-1)) ANP infusion did not affect renal sodium handling in patients with SCD but increased fractional sodium excretion by 0.34 +/- 0.22% (P = 0.003) in control subjects. High-dose (2 microg/min) ANP increased natriuresis to a similar extent in both groups. Insulin's antinatriuretic effects predominated over the natriuretic effects of low-dose, but not high-dose, ANP. These data suggest that insulin's antinatriuretic effect is localized at a distal tubular site other than the long loops of Henle and that the long loops are involved in the natriuretic effect of low-dose ANP, possibly mediated by changes in medullary blood flow.

Effect of insulin treatment on the body composition of Type 2 diabetic patients

“…The composition of weight gain during insulin treatment is not well understood. Insulin exerts an anabolic effect on both lipid and protein metabolism, as well as promoting water and salt retention [6,7]. One should therefore expect a combination of changes in fat‐free mass and fat mass.…”

“…It follows on from this that hydration needs to remain constant if body compartments (FFM hence FM) are to be calculated accurately from body water spaces [11]. However, insulin induces water and sodium retention [6,7] and so modifies hydration, which was confirmed in the present study. Hydration can also be modified by improving glycaemic control [13,26].…”

‘Glucose control-related’ and ‘non-glucose control-related’ effects of insulin on weight gain in newly insulin-treated type 2 diabetic patients

“…It may also be, as suggested by Packianathan et al (2004), that changes in the hydration status lead to erroneous evaluations of TBW itself. Insulin induces water and Na retention (De Fronzo, 1981;Ter Maaten et al 2000) hence may modify hydration. Hydration can also be modified by improving glycaemic control (Brizzolara et al 1996;Bagg et al 2001).…”

“…Insulin exerts an anabolic effect on both adipose and muscle tissue, and leads to water and Na retention (De Fronzo, 1981;Nair et al 1987;Pacy et al 1989;Ter Maaten et al 2000;Packianathan et al 2005). Its antinatriuretic effect is preserved in insulin-resistant states, such as that observed in type 2 diabetes (Ter Maaten et al 1999).…”

Sickle Cell Disease

“…17 Hormone infusion studies have helped to localize sites of action in the kidney. Failure of low-dose infusion of atrial natriuretic peptide (ANP) to increase natriuresis in sickle cell anemia 25 suggests that ANP at this dosage exerts its natriuretic effect in the long loops of Henle of the juxtamedullary nephrons, whereas insulin induces a similar sodium retention in patients with sickle cell anemia and normal subjects, 25 suggesting that its antinatriuretic effect is probably localized at a distal tubular site other than the long loops of Henle. Urinary endothelin 1 is elevated in asymptomatic sickle cell disease patients.…”