%0 Journal Article
%T Insulin Resistance, Obesity, Hypertension, and Renal Sodium Transport
%A Shoko Horita
%A George Seki
%A Hideomi Yamada
%A Masashi Suzuki
%A Kazuhiko Koike
%A Toshiro Fujita
%J International Journal of Hypertension
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/391762
%X Sodium transport through various nephron segments is quite important in regulating sodium reabsorption and blood pressure. Among several regulators of this process, insulin acts on almost all the nephron segments and is a strong enhancer of sodium reabsorption. Sodium-proton exchanger type 3 (NHE3) is a main regulator of sodium reabsorption in the luminal side of proximal tubule. In the basolateral side of the proximal tubule, sodium-bicarbonate cotransporter (NBCe1) mediates sodium and bicarbonate exit from tubular cells. In the distal nephron and the connecting tubule, epithelial sodium channel (ENaC) is of great importance to sodium reabsorption. NHE3, NBCe1, and ENaC are all regulated by insulin. Recently with-no-lysine (WNK) kinases, responsible for familial hypertension, stimulating sodium reabsorption in the distal nephron, have been found to be also regulated by insulin. We will discuss the regulation of renal sodium transport by insulin and its roles in the pathogenesis of hypertension in insulin resistance. 1. Introduction Obesity is frequently accompanied with hypertension [1]. Obesity is, at the same time, closely related to hyperinsulinemia and insulin resistance [2]. While the precise mechanism of hypertension in insulin resistance remains to be clarified, the activation of sympathetic nerve system, the disorders dysregulation of central nerve system including leptin, and the activation of renin-angiotensin system are generally thought to be involved [1]. Although insulin has powerful stimulatory effects on renal sodium transport, it remains controversial whether hyperinsulinemia itself is a cause of hypertension. Acute studies suggest that hyperinsulinemia may cause sodium retention and increased sympathetic activity, which will be an important cause of hypertension [3]. On the other hand, hyperinsulinemia due to insulinoma or chronic insulin infusion into animals do not significantly elevate blood pressure [4, 5]. Moreover, insulin itself has vasodilatory actions [6], which is dependent on nitric oxide [7]. Thus, the relationship between hyperinsulinemia and hypertension is not obvious. However, the influence of insulin on blood pressure may be altered in insulin resistance. For example, the insulin-induced vasodilation is impaired due to defects in PI3-kinase signaling in insulin resistance [8, 9]. Moreover, several recent data suggest that the insulin-induced enhancement of renal sodium reabsorption is preserved or even enhanced in insulin resistance [10¨C12]. For example, Rocchini et al. showed that, in obese subjects with insulin
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