Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited

Silva, Alexandre A. da; Carmo, Jussara M. do; Li, Xuan; Wang, Zhen; Mouton, Alan J.; Hall, John E.

doi:10.1016/j.cjca.2020.02.066

Cited by 198 publications

(137 citation statements)

References 130 publications

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“…[45] Based on epidemiological studies, there exists a positive correlation between hyperinsulinemia or insulin resistance, and elevated BP. [47] However, evidence from human and experimental studies supports the major role of hyperinsulinemia in exacerbating hypertension, but not in initiating hypertension. [48][49][50] MC bioactive components, such as charantin, polypeptide-p and phenolic compounds, might be capable of stimulating insulin secretion, improving insulin sensitivity and facilitating the recovery of damaged pancreatic islet beta cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of Momordica charantia L on blood pressure: a systematic review and meta- analysis of randomized clinical trials

Jandari

Ghavami

Ziaei

et al. 2020

International Journal of Food Properties

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Several reports have indicated a positive effect of Momordica charantia (MC) on blood pressure (BP); nevertheless, these findings have been controversial. Therefore, a systematic review and meta-analysis of randomized controlled trials (RCTs) were aimed to investigate the effects of MC supplementation on BP. PubMed, Scopus, ISI Web of Science, and Cochrane library databases were searched (up to June 2020) to identify RCTs investigating the effects of Momordica charantia supplementation on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Weighted mean differences (WMD) were pooled using a random-effects model. Publication bias was assessed by Egger's and Begg's test and heterogeneity was evaluated using Q tests and the I 2 statistic. Eventually, only five articles (six treatment arms) 305 participants (154 as intervention group/151 as control), which reported data of interest entered for data analysis. The meta-analysis showed a non-significant reduction in SBP (WMD: −2.28 mmHg; 95% CI: −6.62, 2.05, P = .302), with significant heterogeneity between selected studies (I 2 = 77.3%) and (WMD: −0.8 mmHg, 95% CI: −2.65 to 1.04, P = .394) with significant between-study heterogeneity (I 2 = 38.1%). When studies were categorized based on participants' mean age and duration of intervention, SBP and DBP had a large non-significant decrease in subjects with equivalent and less than 50 years' subset and short duration (≤8 weeks'). Consumption of MC preparations was not associated with a significant reduction in either SBP or DBP. However, we found a significant hypotensive effect of MC in younger adults and in short-term interventions. Future adequately powered clinical trials, with larger sample size, which consider proper standardization of MC preparations and exclusively include hypertensive patients, are needed to investigate the clinical potential of MC on blood pressure control among these patients.

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Section: Discussionmentioning

confidence: 99%

Effects of Momordica charantia L on blood pressure: a systematic review and meta- analysis of randomized clinical trials

Jandari

Ghavami

Ziaei

et al. 2020

International Journal of Food Properties

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“…Signaling of insulin occurs via insulin receptor substrate 2 (IRS2) and is not suppressed during insulin resistance, while signaling via IRS1 for counterregulatory mechanisms, including local NO production, is impaired [85,86]. These detrimental actions may be mitigated during chronic hyperinsulinemia/insulin resistance [87]. However, a meta-analysis of 11 prospective epidemiological studies showed that the pooled relative risk of hypertension was 1.54 when comparing the highest to the lowest category of fasting insulin levels, and 1.43 for comparing highest to lowest (selective) insulin resistance categories, calculated as homeostasis model assessment of insulin resistance (HOMA-IR) [88].…”

Section: Detrimental Combination Of Hyperinsulinemia With Insulin Resmentioning

confidence: 99%

Insulin: too much of a good thing is bad

Kolb

Kempf

Röhling

et al. 2020

BMC Med

144

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Background: Insulin shares a limited physiological concentration range with other endocrine hormones. Not only too low, but also too high systemic insulin levels are detrimental for body functions. Main body: The physiological function and clinical relevance of insulin are usually seen in association with its role in maintaining glucose homeostasis. However, insulin is an anabolic hormone which stimulates a large number of cellular responses. Not only too low, but also excess insulin concentrations are detrimental to the physiological balance. Although the glucoregulatory activity of insulin is mitigated during hyperinsulinemia by dampening the efficiency of insulin signaling ("insulin resistance"), this is not the case for most other hormonal actions of insulin, including the promotion of protein synthesis, de novo lipogenesis, and cell proliferation; the inhibition of lipolysis, of autophagy-dependent cellular turnover, and of nuclear factor E2-related factor-2 (Nrf2)-dependent antioxidative; and other defense mechanisms. Hence, there is no general insulin resistance but selective impairment of insulin signaling which causes less glucose uptake from the blood and reduced activation of endothelial NO synthase (eNOS). Because of the largely unrestricted insulin signaling, hyperinsulinemia increases the risk of obesity, type 2 diabetes, and cardiovascular disease and decreases health span and life expectancy. In epidemiological studies, high-dose insulin therapy is associated with an increased risk of cardiovascular disease. Randomized controlled trials of insulin treatment did not observe any effect on disease risk, but these trials only studied low insulin doses up to 40 IU/day. Proof for a causal link between elevated insulin levels and cardiovascular disease risk comes from Mendelian randomization studies comparing individuals with genetically controlled low or high insulin production. Conclusions: The detrimental actions of prolonged high insulin concentrations, seen also in cell culture, argue in favor of a lifestyle that limits circadian insulin levels. The health risks associated with hyperinsulinemia may have implications for treatment regimens used in type 2 diabetes.

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“…The cellular and molecular mechanisms shared between hypertension and T2D include insulin resistance, increased activation of the renin-angiotensin-aldosterone system (RAAS), oxidative stress, and endothelial dysfunction [ 29 , 30 ]. Insulin resistance and its associated hyperinsulinemia increases oxidative stress and reactive oxygen species (ROS) production via NADPH oxidase imbalance, which increases metabolic flux of the polyol (sorbitol) pathway and increases production of advanced glycation end products (AGE), acti133vation of protein kinase C, and others [ 31 – 33 ].…”

Section: Introductionmentioning

confidence: 99%

“…Insulin resistance and its associated hyperinsulinemia increases oxidative stress and reactive oxygen species (ROS) production via NADPH oxidase imbalance, which increases metabolic flux of the polyol (sorbitol) pathway and increases production of advanced glycation end products (AGE), acti133vation of protein kinase C, and others [ 31 – 33 ]. Likewise, increased RAAS activation, a well-known contributor to hypertension [ 34 , 35 ], increases sympathetic outflow and increases vascular ROS and contributes to endothelial cell senescence, vascular aging [ 36 ••], and high blood pressure [ 30 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

Hypertension and Age-Related Cognitive Impairment: Common Risk Factors and a Role for Precision Aging

et al. 2020

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Purpose of Review Precision Aging® is a novel concept that we have recently employed to describe how the model of precision medicine can be used to understand and define the multivariate risks that drive age-related cognitive impairment (ARCI). Hypertension and cardiovascular disease are key risk factors for both brain function and cognitive aging. In this review, we will discuss the common mechanisms underlying the risk factors for both hypertension and ARCI and how the convergence of these mechanisms may be amplified in an individual to drive changes in brain health and accelerate cognitive decline. Recent Findings Currently, our cognitive health span does not match our life span. Age-related cognitive impairment and preventing and treating ARCI will require an in-depth understanding of the interrelated risk factors, including individual genetic profiles, that affect brain health and brain aging. Hypertension and cardiovascular disease are important risk factors for ARCI. And, many of the risk factors for developing hypertension, such as diabetes, smoking, stress, viral infection, and age, are shared with the development of ARCI. We must first understand the mechanisms common to the converging risk factors in hypertension and ARCI and then design person-specific therapies to optimize individual brain health. Summary The understanding of the convergence of shared risk factors between hypertension and ARCI is required to develop individualized interventions to optimize brain health across the life span. We will conclude with a discussion of possible steps that may be taken to decrease ARCI and optimize an individual's cognitive life span.

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Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited

Cited by 198 publications

References 130 publications

Effects of Momordica charantia L on blood pressure: a systematic review and meta- analysis of randomized clinical trials

Effects of Momordica charantia L on blood pressure: a systematic review and meta- analysis of randomized clinical trials

Insulin: too much of a good thing is bad

Hypertension and Age-Related Cognitive Impairment: Common Risk Factors and a Role for Precision Aging

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