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. Author manuscript; available in PMC: 2021 Mar 31.
Published in final edited form as: Curr Pharm Des. 2020;26(30):3760–3767. doi: 10.2174/1381612826666200721002735

Fig. (1). Effects of Insulin and pharmacological agents on endothelial insulin signaling.

Fig. (1).

Shown are the effects of Insulin, TZDs, Metformin, and Vildagliptin on endothelial insulin signaling and downstream vasorelaxation, vasoconstriction, and glucose uptake. Question marks represent places in which mechanisms are unknown throughout the available literature. Illustrated here is the PI3K signaling pathway downstream of insulin receptor activation resulting in NO production and vasodilation. Shown in tandem is the metabolic and mitogenic pathway of insulin receptor activation which controls the secretion of endothelin-1 and leads to vasoconstriction. Also displayed are the molecular targets of metformin acting as an activator of AKT downstream of PI3K as well as stimulating AMPK. TZDs are shown here also stimulating both PI3K as well as PPARγ which in conjunction increase glucose uptake and NO production. Vildagliptin is presented as a DPP-4 inhibitor with downstream effects on eNOS, subsequently increasing NO levels which result in vasorelaxation.