Table 3 Deleterious effects of hyperinsulinemia (HI)

1.

HI, hyperproinsulinemia, and hyperamylinemia synergistically activate RAS with subsequent increase in Ang II, renin, and aldosterone.

2.

HI promotes Na⁺ and H₂O retention, which increases blood volume and pressure. In turn this activates the reabsorption of uric acid resulting in elevation of SUA. In turn increased SUA has been shown to increase tubular reabsorption of Na+.

3.

HI increases membrane cation-transport increasing intracellular Ca⁺⁺, which increases tone and pressure.

4.

HI activates the sympathetic nervous system.

5.

HI stimulates vSMC proliferation and migration and remodeling.

6.

HI increases the number of AT-1 receptors.

7.

HI creates cross talk between the insulin receptor and AT-1 receptor, resulting in a more profound Ang II effect.

8

HI promotes PI3 kinase Akt-MAP kinase Shunt. Impairing the metabolic (PI3 kinase-AKT pathway while promoting the MAPkinase remodeling pathway.

9.

HI induces Ang II, which promotes the MAP kinase pathway and remodeling.

10.

HI induces Ang II, which is the most potent stimulus for production of NAD(P)H oxidase with reactive oxygen species generation (superoxide production) and resultant vascular oxidative stress.