Wednesday, January 6, 2010

SGK1, Hypertension and the Metabolic Syndrome

I was recently asked the mechanism by which insulin resistance causes sodium retention and hypertension, and had to lie. Here's what I should have said.

Serum and glucocorticoid-inducible kinase 1 (SGK1) is an enzymatic central orchestrator of many renal processes and electrolyte balance, and is the likely cause of sodium retention and hypertension in insulin resistance states such as the metabolic syndrome. SGK1 transcription is stimulated by a wide variety of factors, most notably insulin, glucocorticoids, activated Vit D, PPAR gamma agonists and ischemia. Teleologically, the SGK1 system probably developed to permit the excretion of the large amounts of potassium, and conservation of the relatively low amounts of sodium, present in the diets of the Paleolithic era. To acheive this, activation results in the stimulation of the following cellular processes:


- Stimulation of renal ion channels, incl. ENaC, ROMK, TRPV5, N/K ATPase and voltage-gated K channels
- Regulation of mineralocorticoid stimulation of salt appetite
- Glucocorticoid stimulation of the Na+/H+ exchanger and nutrient transport
- Insulin-dependant salt sensitivity of blood pressure
- Salt -sensitivity of peripheral glucose uptake

Interestingly, an SGK1 gene variant present in 3-5% of Caucasians and 10% of African Americans is associated with obesity, hypertension and the development of diabetes. Here's a short review from a recent NephSAP editorial (beginning on page 61), from which the adjacent diagram was also taken.

1 comment:

  1. Starving is not the answer, sooner or later your body will succumb to hunger and these will result to a whole lot of eating.

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