INS and cerebral small vessel disease: Moreover, insulin infusion during euglycemic insulin clamp was able to suppress endothelium-dependent vasodilation in large arteries, which is reported to be based on increased availability of endothelin-1, leading to downregulation of NAD(P)H oxidase and superoxide anion production [22], and endothelial dysfunction is proposed to play an important role in the pathogenesis of cerebral small vessel disease [23, 24].