Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease

Abstract

Impaired insulin signaling is central to development of the metabolic syndrome and can promote cardiovascular disease indirectly through development of abnormal glucose and lipid metabolism, hypertension, and a proinflammatory state. However, insulin's action directly on vascular endothelium, atherosclerotic plaque macrophages, and in the heart, kidney, and retina has now been described, and impaired insulin signaling in these locations can alter progression of cardiovascular disease in the metabolic syndrome and affect development of microvascular complications of diabetes mellitus. Recent advances in our understanding of the complex pathophysiology of insulin's effects on vascular tissues offer new opportunities for preventing these cardiovascular disorders.

Figure 1. Physiology of insulin signaling in metabolic syndrome

Overview of the physiology of insulin signaling in the metabolic syndrome. Insulin actions which are insulin resistant in metabolic syndrome are labeled in red, whereas insulin actions which remain insulin sensitive in metabolic syndrome are labeled in green.

Figure 2. Molecular mechanisms of insulin signaling

Important insulin signaling pathways in various cell types. Abbreviations: IR, insulin receptor; LDLR, low density lipoprotein receptor; MHC, myosin heavy chain; mTORC1, mammalian target of rapamycin complex 1; PCSK9, proprotein convertase subtilisin/kexin type 9; PKA, protein kinase A; TNF, tumor necrosis factor-α. For other abbreviations, please see text.