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. Author manuscript; available in PMC: 2020 Jun 1.
Published in final edited form as: J Mol Cell Cardiol. 2019 Apr 20;131:82–90. doi: 10.1016/j.yjmcc.2019.04.015

Fig. 8.

Fig. 8.

Proposed signaling sequence for the development of coronary arteriolar dysfunction by diabetes/hyperglycemia. Under normal conditions, serotonin activates eNOS in the endothelium of coronary arterioles leading to the production of NO from the substrate L-arginine and subsequent dilation. During prolonged hyperglycemia of type 1 diabetes, endothelial LOX-1 in coronary arterioles is activated with subsequent downstream signaling via JNK and arginase-I causing a reduction in L-arginine availability for eNOS. In the absence of sufficient levels of L-arginine, eNOS produces superoxide anions (O2•−), which scavenge NO and reduce endothelium-dependent vasodilation (represented by dashed lines).