Contribution of salt intake to insulin resistance associated with hypertension.
It is well-known that excessive salt intake induces elevation of blood pressure and that hypertension often coexists with insulin resistance. However, the contribution made by salt intake to the development of insulin resistance remains unclear. In this minireview, the insulin resistance seen in three salt-sensitive rat models (the high-salt-fed Sprague-Dawley rat, the Dahl salt-sensitive rat and the chronically angiotensin II (AII)-infused rat) are presented. One notable observation common to all three models was that, despite their insulin-resistance, the early insulin signaling steps leading from activation of IR and IRSs to activation of PI 3-kinase Akt were apparently enhanced. This suggests that the molecular mechanism underlying the insulin resistance related to the salt-sensitive hypertension is unique. Other factors known to cause insulin resistance--e.g., obesity--actually suppress early insulin signaling, but for insulin resistance related to high-salt intake, the impaired step must be further downstream in the insulin signaling pathway. What's more, increased oxidative stress appears to be crucially involved in both AII- and high-salt-induced insulin resistance. Additional study will be necessary to fully clarify the mechanism underlying insulin resistance induced by a high-salt diet; nonetheless, the findings presented suggest the importance of developing new therapeutic approaches--e.g., potassium supplementation and anti-oxidant administration--to the treatment of insulin resistance and hypertension.
Ogihara
Takehide
T
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan.
Asano
Tomoichiro
T
Fujita
Toshiro
T
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017419:Potassium, Dietary / Q000008:administration & dosage; D051381:Rats; D020303:Rats, Inbred Dahl; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
D007328:Insulin; D017419:Potassium, Dietary; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II