Insulin Resistance and High Blood Pressure: Mechanistic Insight on the Role of the Kidney

Abstract

The metabolic effects of insulin predominate in skeletal muscle, fat, and liver where the hormone binds to its receptor, thereby priming a series of cell-specific and biochemically diverse intracellular mechanisms. In the presence of a good secretory reserve in the pancreatic islets, a decrease in insulin sensitivity in the metabolic target tissues leads to compensatory hyperinsulinemia. A large body of evidence obtained in clinical and experimental studies indicates that insulin resistance and the related hyperinsulinemia are causally involved in some forms of arterial hypertension. Much of this involvement can be ascribed to the impact of insulin on renal sodium transport, although additional mechanisms might be involved. Solid evidence indicates that insulin causes sodium and water retention, and both endogenous and exogenous hyperinsulinemia have been correlated to increased blood pressure. Although important information was gathered on the cellular mechanisms that are triggered by insulin in metabolic tissues and on their abnormalities, knowledge of the insulin-related mechanisms possibly involved in blood pressure regulation is limited. In this review, we summarize the current understanding of the cellular mechanisms that are involved in the pro-hypertensive actions of insulin, focusing on the contribution of insulin to the renal regulation of sodium balance and body fluids.

Assessment of eight insulin resistance surrogate indexes for predicting metabolic syndrome and hypertension in Thai law enforcement officers

“…Therefore, research is needed to be considered as a significant indicator for predicting hypertension and MetS, which should help reduce the risk of hypertension and MetS in police personnel promptly. Insulin resistance has been found to play a significant causal role in developing hypertension ( Brosolo et al, 2022 ) and cardiovascular diseases ( Di Pino & DeFronzo, 2019 ). Endothelial dysfunction, vascular resistance, the activity of the sympathetic nervous system, renal sodium and fluid retention, and the subsequent renin-angiotensin-aldosterone system may play a crucial part in the etiology of hypertension when insulin resistance is present ( Brosolo et al, 2022 ; Janus et al, 2016 ).…”

“…Insulin resistance has been found to play a significant causal role in developing hypertension ( Brosolo et al, 2022 ) and cardiovascular diseases ( Di Pino & DeFronzo, 2019 ). Endothelial dysfunction, vascular resistance, the activity of the sympathetic nervous system, renal sodium and fluid retention, and the subsequent renin-angiotensin-aldosterone system may play a crucial part in the etiology of hypertension when insulin resistance is present ( Brosolo et al, 2022 ; Janus et al, 2016 ). The previous report indicated the correlation between the LAP, TG/HDL-c, TyG index and VAI with a HOMA-IR, which reflex the predictive ability of insulin resistance by these indices ( Huang et al, 2022 ).…”

Insulin resistance/hyperinsulinemia: an important cardiovascular risk factor that has long been underestimated

“…Therefore, under IR/Hyperins conditions, the excessive stimulation of the MAPK cascade, which has vasoconstrictive (↥ ET-1) and growth-promoting effects at various cellular levels, ends up determining part of the deleterious effects at the cardiovascular level. At this point there is also solid evidence to support the fact that Hyperins may also be a determinant of arterial hypertension, in fact it has been demonstrated that insulin causes retention of sodium and water in the kidney, and that both endogenous and exogenous Hyperins were found related to increases in blood pressure ( 28 ) ( Figure 1 ). In fact, insulin receptors have been detected in the renal tubules, and their stimulation by insulin has been shown to produce increased sodium reabsorption.…”

Association of arterial stiffness with a prothrombotic state in uncomplicated nondiabetic hypertensive patients

“…Causes of secondary hypertension were ruled out according to current guidelines (35) after clinical, biochemical (urine analysis, creatinine clearance, plasma aldosterone, renin, and cortisol, free urinary cortisol and epinephrine, norepinephrine, and dopamine) and instrumental tests (ECG, echocardiography, renal ultrasound, and renal angio-CT and adrenal CT scan when indicated) (36). Diabetes was excluded by measurement of fasting blood glucose and glycated hemoglobin, and by a standard oral glucose tolerance test (37). Smokers were defined if they smoked for more than 5 years and did not quit more than 1 year before examination.…”