The Injurious Effects of Hyperinsulinism on Blood Vessels

Abstract

Insulin resistance (IR) is a common feature of hypertension, Type II diabetes, coronary heart disease, Syndrome X, and other vascular diseases. It refers to a state in which a certain concentration of insulin produces less biologic effect than expected in human body. When IR develops, the response of human body to insulin decreases accordingly, thus inducing the compensatory hyper-secretion of insulin and consequently hyperinsulinism. Many clinical and epidemiologic studies have demonstrated that IR and iatrogenic hyperinsulinism induced consequently play an essential role in the pathogenesis of hypertension and atherosclerotic cardiovascular diseases. Therefore, more and more attention should be paid to the mechanism of IR in order to explore more therapeutic basis and prospective for the treatment of atherosclerosis and other cardiovascular diseases. In this review, we provided a general overview on the known molecular mechanisms of IR and summarized the recent findings on the injurious effects of hyperinsulinism in vitro and in vivo, which might be important for researchers and clinicians to better understand the etiology and clinical significance of IR.

Importance of the route of insulin delivery to its control of glucose metabolism

“…Insulin is the key regulator of liver glucose metabolism, but its effectiveness depends on several factors, including how it is distributed across the body. Of note, arterial hyperinsulinemia is associated with metabolic and cardiovascular disease and hypoglycemic risk and is a contributor to type 2 diabetes (2,(13)(14)(15)(16)(17)(18).…”

KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways

“…Type 2 DM is comprised of complex metabolic disorders, including hyperglycemia, hyperlipidemia and hyperinsulinemia ( 21 ). Experimental studies have demonstrated that high concentrations of insulin may confer direct or indirect effects on amplifying cardiovascular stress ( 15 ). Abhijit et al reported that VSMCs exposed to hyperinsulinemia may exhibit increased ROS generation ( 27 ).…”

“…In addition, Shiny et al and Martínez-Hervás et al provided evidence to suggest that hyperinsulinemia aggravates the inflammatory response and reduces VSMC survival, respectively ( 28 , 29 ). It is well documented that ROS and inflammation may induce VSMC proliferation and migration ( 15 , 27 , 28 ); however, the association between apoptosis and VSMC dysfunction remains debatable; a study has indicated that apoptosis may also trigger VSMC proliferation, leading to neointimal hyperplasia ( 30 ); however, the underlying mechanisms of this phenomenon are unclear ( 30 ). In line with previous studies, the present study indicated that stimulation with high concentration insulin promoted VSMC dysfunction and pathological injuries.…”

“…Liu et al previously demonstrated that insulin-mediated proliferation of VSMCs could be suppressed by PD98059, a selective inhibitor of the ERK1/2 signaling pathway, thus suggesting that MAPKs have a regulatory impact on insulin-induced VSMC injuries ( 35 ). Oxidative stress and inflammation are vital factors associated with VSMC dysfunction; therefore, any factor that increases oxidative stress and inflammation may lead to VSMC injuries ( 15 ). ERK, JNK, p38 MAPK and NF-κB are all ROS-sensitive regulators ( 36 ).…”

“…It has previously been reported that abnormal serum insulin levels are capable of promoting the progression of atherosclerosis ( 14 ). In addition, increased proliferation and migration of VSMCs, as well as increased oxidative stress and inflammation, may be closely linked ( 15 ). Further attention should therefore be paid to elucidate the molecular mechanisms underlying hyperinsulinemia-induced VSMC dysfunction, in order to identify potential targets and novel therapeutic approaches for the treatment of DM-associated cardiovascular complications.…”