Although the role of insulin resistance in the pathogenesis of diabetes was. The inter-relationship between insulin resistance and hypertension. Salvetti A(1), Brogi G, Di Legge V, Bernini GP. Author information: (1)Cattedra di Medicina. Some reports suggested that insulin resistance syndrome. (IRS) is associated with hypertension, while others did not support this view The.
All subjects were nondiabetic, without evidence of cardiovascular disease on the basis of medical history, and a normal electrocardiogram at rest and in response to exercise. Blood was drawn after an overnight fast for determination of plasma glucose, insulin, and NOx concentrations. In the case of patients with hypertension, BP-lowering drugs were stopped 3 days before obtaining the blood samples.
Plasma glucose and insulin concentrations were determined as described previously. Finally, Griess reactives were added to each well and the sample read at nm.
A normotensive insulin resistant group N-IR was created from the Barilla study participants to be comparable to the two hypertensive groups in terms of age, gender distribution, body mass index BMIand waist circumference, and to have fasting plasma insulin concentrations similar to the EH-IR subjects.
The relationship between fasting plasma insulin and NOx concentrations in the 78 patients with EH was evaluated by both simple Pearson linear regression analysis and multivariate general linearized model GLM analysis.
In the distal nephron and the connecting tubule, epithelial sodium channel ENaC is of great importance to sodium reabsorption. Recently with-no-lysine WNK kinases, responsible for familial hypertension, stimulating sodium reabsorption in the distal nephron, have been found to be also regulated by insulin.
Link between Insulin Resistance and Hypertension: What Have We Learned from Our Ancestors?
We will discuss the regulation of renal sodium transport by insulin and its roles in the pathogenesis of hypertension in insulin resistance. Introduction Obesity is frequently accompanied with hypertension [ 1 ]. Obesity is, at the same time, closely related to hyperinsulinemia and insulin resistance [ 2 ].
While the precise mechanism of hypertension in insulin resistance remains to be clarified, the activation of sympathetic nerve system, the disorders dysregulation of central nerve system including leptin, and the activation of renin-angiotensin system are generally thought to be involved [ 1 ].
Although insulin has powerful stimulatory effects on renal sodium transport, it remains controversial whether hyperinsulinemia itself is a cause of hypertension.
Acute studies suggest that hyperinsulinemia may cause sodium retention and increased sympathetic activity, which will be an important cause of hypertension [ 3 ]. On the other hand, hyperinsulinemia due to insulinoma or chronic insulin infusion into animals do not significantly elevate blood pressure [ 45 ].
Moreover, insulin itself has vasodilatory actions [ 6 ], which is dependent on nitric oxide [ 7 ].
Thus, the relationship between hyperinsulinemia and hypertension is not obvious. However, the influence of insulin on blood pressure may be altered in insulin resistance.
For example, the insulin-induced vasodilation is impaired due to defects in PI3-kinase signaling in insulin resistance [ 89 ]. Moreover, several recent data suggest that the insulin-induced enhancement of renal sodium reabsorption is preserved or even enhanced in insulin resistance [ 10 — 12 ].
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For example, Rocchini et al. These considerations support a significant role of insulin-stimulated renal sodium transport in the pathogenesis of hypertension in insulin resistance.
This review will focus mainly on the regulation of sodium reabsorption along the nephron segments by insulin and its roles in the blood pressure control. Figure 1 shows the main sodium transporters and regulators discussed in this review.
Insulin Acting Sites upon Nephron It has been known for a long time, that insulin acts upon the whole nephron. In rat nephron, Butlen et al. The way that insulin arrives at the nephron seems to be by two ways: The former is by glomerular filtration and subsequent reabsorption from tubular cells by endocytosis, the latter is diffusion from peritubular capillaries and subsequent binding to the receptor.
Insulin and Renal Proximal Absorption Insulin uptake in the renal proximal tubule has been reported on animals such as rabbits [ 13 ], rats [ 17 ], and dogs [ 18 ].
Importantly, insulin has been known to enhance sodium reabsorption in the proximal tubule [ 19 ]. Insulin stimulates not only sodium but also volume absorption in the rabbit proximal convoluted tubule. Regarding these stimulatory effects, insulin acts only from the basolateral side of the tubule, not from the luminal side [ 20 ].
Proximal tubules reabsorb about seventy percents of total Na filtered from glomeruli. This is important because NHE3 plays a major role in apical sodium entry in proximal tubules. Obesity is a common cause of insulin resistance.
The epidemic-like rise in the prevalence of obesity constitutes an undoubted and serious global health problem [ 56 ]. Importantly, hypertension and diabetes are associated with obesity and together, constitute a significant burden in terms of patient morbidity and mortality as well as escalating health care costs [ 7 ]. Stocking up on food was key to survival in pre-modern times, but now with energy dense and cheap foods, labor-saving devices, motorized transport and sedentary work, obesity is rapidly becoming a consequence of modern life.
Insulin Resistance, Obesity, Hypertension, and Renal Sodium Transport
Many studies suggest that obesity is associated with a systemic chronic inflammatory response characterized by altered proinflammatory cytokine production and activation of inflammatory signaling pathways in adipose tissue [ 89 ]. Clinical and experimental studies have provided ample evidence showing a close link between chronic inflammation and insulin resistance in obesity [ 10 ]. However, insulin resistance also exists in malnourished populations and is mechanistically linked to inflammation [ 11 ].
Evolution by natural selection is a central organizing concept in biology. For millions of years, living beings from lower-level organisms to human beings have been faced with survival stresses, including malnutrition and infection. Survival of multicellular organisms depends on the ability to store energy for times of low nutrient availability or high energy need and the ability to fight infections [ 12 ].The link between type 2 diabetes and hypertension
The metabolic and immune systems are therefore among the most basic requirements across the animal kingdom [ 13 ]. It is not surprising then that metabolic and immune pathways have evolved to be closely linked and interdependent, and that the genes that control metabolic and pathogen-sensing systems have been highly conserved from lower-level organisms to mammals [ 11 ].
Under normal conditions, the integration of the metabolic and immune systems is fundamental for the maintenance of good health. It has been well recognized that there is a link between infection and poor nutrition. The basic inflammatory response favors a catabolic state and inhibits anabolic pathways, such as the highly conserved insulin signaling pathway, and consequently results in insulin resistance.
As a result of insulin resistance, plasma levels of glucose are elevated to provide energy sources to maintain the function of vital organs, such as the heart and brain, and of immune cells, such as leukocytes, to combat infection, since the heart, brain and leukocytes are dependent on plasma levels of glucose for energy.