Published Online
on June 3, 2002

A more recent version of this article appeared on July 1, 2002

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Submitted on February 12, 2002
Revised on March 15, 2002

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats

Takehide Ogihara; Tomoichiro Asano^*; Katsuyuki Ando; Hideyuki Sakoda; Motonobu Anai; Nobuhiro Shojima; Hiraku Ono; Yukiko Onishi; Midori Fujishiro; Miho Abe; Yasushi Fukushima; Masatoshi Kikuchi; and Toshiro Fujita

From the Department of Internal Medicine, Graduate School of Medicine, University of Tokyo (T.O., T.A., K.A., N.S., M.F., M.Ab., Y.F., T.F.), Tokyo; and the Institute for Adult Diseases, Asahi Life Foundation (T.O., H.S., M.An., H.O., Y.O., M.K.), Tokyo, Japan.

^* To whom correspondence should be addressed. E-mail: asano-tky{at}umin.ac.jp.

Abstract—A high-salt diet, which is known to contribute to the pathogenesis of hypertension, is also reportedly associated with insulin resistance. We investigated the effects of a high-salt diet on insulin sensitivity and insulin signaling in salt-sensitive (Dahl-S) and salt resistant (Dahl-R) strains of the Dahl rat. Evaluation of hyperinsulinemic-euglycemic clamp studies and glucose uptake into the isolated soleus muscle revealed that salt loading (8% NaCl) for 4 weeks induced hypertension and significant insulin resistance in Dahl-S rats, whereas no significant effects were observed in Dahl-R rats. Despite the presence of insulin resistance, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrates, activation of phosphatidylinositol 3-kinase, and phosphorylation of Akt were all enhanced in Dahl-S rats fed a high-salt diet. The mechanism underlying this form of insulin resistance thus differs from that previously associated with obesity and dexamethasone and is likely due to the impairment of one or more metabolic steps situated downstream of phosphatidylinositol 3-kinase and Akt activation. Interestingly, supplementation of potassium (8% KCl) ameliorated the changes in insulin sensitivity in Dahl-S rats fed a high-salt diet; this was associated with a slight but significant decrease in blood pressure. Evidence presented suggest that there is an interdependent relationship between insulin sensitivity and salt sensitivity of blood pressure in Dahl-S rats, and it is suggested that supplementing the diet with potassium may exert a protective effect against both hypertension and insulin resistance in salt-sensitive individuals.

Key words: hypertension, sodium-dependent • insulin resistance • potassium • rats, Dahl • kinase

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