Many processes have been described to drive insulin resistance, among which excessive InsR stimulation in a context of hyperinsulinemia, leading to increased InsR recycling and subsequent reduced InsR molecules at the plasma membrane, and spatiotemporal inhibition of insulin-evoked signaling, through dephosphorylation of activating tyrosine residues, phosphorylation of inhibitory serine/threonine residues, or dephosphorylation of PI3K lipid products. The gene discussed is INSR; the disease is hyperinsulinism.