Essential Hypertension Is Associated With Decreased Insulin Clearance and Insulin Resistance

Lender, Dan; Arauz-Pacheco, Carlos; Adams‐Huet, Beverley; Raskin, Philip

doi:10.1161/01.hyp.29.1.111

Cited by 49 publications

(47 citation statements)

References 21 publications

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“…4), mimic the pathological features of essential hypertension, a model of chronically reduced vascular NO availability. However, it should be noted that essential hypertension has been associated with reduced insulin clearance [27]. This discrepancy is likely to be explained by the fact that essential hypertension is frequently associated with chronic primary insulin resistance and hyperinsulinaemia, which, in turn, is associated with reduced insulin clearance (due to saturation of first-pass insulin removal).…”

Section: Discussionmentioning

confidence: 99%

Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion

et al. 2013

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Aims/hypothesis Endogenous NO inhibits insulin release in isolated beta cells and insulin-degrading enzyme activity in hepatocytes, while NO release from endothelial cells has been suggested to enhance insulin action. We assessed the overall effect of systemic inhibition of endogenous NO synthesis on glucose homeostasis in humans. Methods Twenty-four non-diabetic volunteers underwent two hyperglycaemic (+7 mmol/l) clamps with either saline or L-NGnitroarginine methyl ester (L-NAME, at rates of 2.5, 5, 10 and 20 μgmin −1 kg −1 ) infusion. Another five volunteers underwent an OGTT with either saline or L-NAME (20 μgmin −1 kg −1 ) infusion. Blood pressure and heart rate were measured to monitor NO blockade; during the OGTT, endothelial function was assessed by peripheral arterial tonometry and insulin secretion by C-peptide deconvolution and insulin secretion modelling. Results Compared with saline, L-NAME at the highest dose raised mean blood pressure (+20±2 mmHg), depressed heart rate (−12±2 bpm) and increased insulin clearance (+50%).First-phase insulin secretion was impaired, but insulin sensitivity (M/I index) was unchanged. During the OGTT, L-NAME raised 2 h plasma glucose by 1.8 mmol/l (p<0.01), doubled insulin clearance and impaired beta cell glucose sensitivity while depressing endothelial function. Conclusions/interpretation In humans, systemic NO blockade titrated to increase blood pressure and induce endothelial dysfunction does not affect insulin action but significantly impairs glucose tolerance by increasing plasma insulin clearance and depressing insulin secretion, namely first-phase and beta cell glucose sensitivity.

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Section: Discussionmentioning

confidence: 99%

Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion

et al. 2013

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“…The lower MSNA and higher FBF achieved during hyperinsulinemia conducted after exercise in healthy subjects suggest that a single bout of exercise could have important clinical implications, especially in some hyperinsulinemic populations, such as obese (10,25,38) and hypertensive (19,28) patients, who present sympathetic activation (2,22,25,27,38) and blunted vasodilation (3,26,38) during acute hyperinsulinemia induced, for example, by a meal. Nevertheless, it is important to point out that the insulin level achieved after meals is lower than the one used in the present study and occurs concomitantly to hyperglycemia (33).…”

Section: Discussionmentioning

confidence: 99%

“…The sympathoexcitatory effect of insulin may have clinical importance in some physiopathological states, such as hypertension and obesity, which commonly present hyperinsulinemia (10,19,25,28,38), sympathetic activation (2,22,27,38), and cardiovascular disturbances (2,22,25,27,38).…”

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confidence: 99%

Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia

Bisquolo¹,

Cardoso²,

Ortega³

et al. 2005

Journal of Applied Physiology

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. Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia. J Appl Physiol 98: 866 -871, 2005. First published November 12, 2004 doi:10.1152/japplphysiol.00251.2004.-Insulin infusion causes muscle vasodilation, despite the increase in sympathetic nerve activity. In contrast, a single bout of exercise decreases sympathetic activity and increases muscle blood flow during the postexercise period. We tested the hypothesis that muscle sympathetic activity would be lower and muscle vasodilation would be higher during hyperinsulinemia performed after a single bout of dynamic exercise. Twenty-one healthy young men randomly underwent two hyperinsulinemic euglycemic clamps performed after 45 min of seated rest (control) or bicycle exercise (50% of peak oxygen uptake). Muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (FBF, plethysmography), blood pressure (BP, oscillometric method), and heart rate (HR, ECG) were measured at baseline (90 min after exercise or seated rest) and during hyperinsulinemic euglycemic clamps. Baseline glucose and insulin concentrations were similar in the exercise and control sessions. Insulin sensitivity was unchanged by previous exercise. During the clamp, insulin levels increased similarly in both sessions. As expected, insulin infusion increased MSNA, FBF, BP, and HR in both sessions (23 Ϯ 1 vs. 36 Ϯ 2 bursts/min, 1.8 Ϯ 0.1 vs. 2.2 Ϯ 0.2 ml ⅐ min Ϫ1 ⅐ 100 ml Ϫ1 , 89 Ϯ 2 vs. 92 Ϯ 2 mmHg, and 58 Ϯ 1 vs. 62 Ϯ 1 beats/min, respectively, P Ͻ 0.05). BP and HR were similar between sessions. However, MSNA was significantly lower (27 Ϯ 2 vs. 31 Ϯ 2 bursts/min), and FBF was significantly higher (2.2 Ϯ 0.2 vs. 1.8 Ϯ 0.1 ml ⅐ min Ϫ1 ⅐ 100 ml Ϫ1 , P Ͻ 0.05) in the exercise session compared with the control session. In conclusion, in healthy men, a prolonged bout of dynamic exercise decreases MSNA and increases FBF. These effects persist during acute hyperinsulinemia performed after exercise.

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“…Decreased insulin clearance may be responsible for this phenomenon. 31 Indeed, decreased blood flow to the liver as a result of angiotensin II 32 can diminish insulin clearance. 33 Thus, the increased insulin level during SSPI in LSD rats may be related to high plasma angiotensin II concentration.…”

Section: Discussionmentioning

confidence: 99%

High- or Low-Salt Diet From Weaning to Adulthood

et al. 2000

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Abstract-Because of conflicting results in the literature, further studies are needed to confirm an association between the degree of salt consumption and insulin sensitivity. The aim of this study was to measure insulin sensitivity in rats fed from weaning to adulthood with a low (LSD), normal (NSD), or high (HSD) salt diet. Body weight, carcass lipid content, blood glucose, nonesterified fatty acids, plasma insulin, plasma renin activity, and a glucose transporter (GLUT4) were measured. A euglycemic hyperinsulinemic clamp was used in 52 anesthetized rats. Body weight was higher in rats on LSD than in those on NSD (PϽ0.05) or HSD (PϽ0.001). Percentage fat carcass content was higher (PϽ0.05) in rats on LSD than in those on NSD. Basal plasma insulin and glucose levels were not altered (PϾ0.05) by salt consumption. Nonesterified fatty acids were lower in rats on HSD than in those on LSD (PϽ0.05) or NSD (PϽ0.01). Glucose uptake was lower in rats on LSD than in those on NSD (PϽ0.05) or HSD (PϽ0.001). When a euglycemic hyperinsulinemic clamp was used on pair-weight rats, similar results were obtained, which suggests that the effect of LSD on insulin sensitivity was not due to higher body weight. GLUT4 in insulin-sensitive tissues was increased in rats on HSD except in the cardiac muscle. Captopril treatment partially reversed low insulin sensitivity in LSD rats, whereas losartan did not change it, which indicates that the effect of LSD on insulin sensitivity is angiotensin independent. In conclusion, the present results demonstrate that chronic dietary salt restriction induces a decrease in insulin sensitivity not associated with renin-angiotensin system activity or body weight changes. Key Words: insulin resistance Ⅲ sodium, dietary Ⅲ insulin Ⅲ captopril Ⅲ angiotensin I nsulin resistance has been shown to occur in hypertensive subjects and has been proposed as a metabolic link between hypertension, non-insulin-dependent diabetes mellitus, obesity, dyslipidemia, and atherosclerotic cardiovascular disease. 1,2 Therefore, in hypertension treatment, consideration should be given to the effect of antihypertensive agents on insulin sensitivity (IS).Salt restriction is recommended for antihypertensive treatment, 3-5 and its effect on IS has been studied by several groups. Most of the studies 6,7 showed that salt restriction lowers IS, although some of them concluded the opposite. 8 Almost all studies from the literature analyzed the effects of short-term changes in salt consumption. However, to better understand the antihypertensive effects of salt restriction on IS, a long-term study was advisable. Recently, we have shown in rats that chronic salt restriction compared with overload is associated with lower blood pressure (BP) and decreased insulin-independent and dependent glucose uptake (GU) in epididymal isolated adipocytes. However, on the basis of the unchanged EC 50 of GU, no alteration on IS was observed. 9 Therefore, the present study was planned to evaluate, by use of the euglycemic hyperinsulinemic clamp (EHC), I...

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Essential Hypertension Is Associated With Decreased Insulin Clearance and Insulin Resistance

Cited by 49 publications

References 21 publications

Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion

Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion

Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia

High- or Low-Salt Diet From Weaning to Adulthood

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