NOX4 and hyperinsulinism: This is perhaps not surprising when one considers that SVEC from patients with type 2 diabetes have been exposed to multiple systemic factors that are not present in mIGFREO (which have increased Nox4 and reduced Nox2 expression in EC) including, but not limited to, hyperglycemia, hyperlipidemia, hyperinsulinemia, and excess circulating cytokines.