Acute noradrenergic activation induces insulin resistance in human skeletal muscle

Lembo, Giuseppe; Capaldo, Brunella; Rendina, Virgilio; Iaccarino, Guido; Napoli, Raffaele; Guida, Raffaele; Trimarco, Bruno; Saccà, Luigi

doi:10.1152/ajpendo.1994.266.2.e242

Cited by 93 publications

(75 citation statements)

References 30 publications

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“…Resting heart rate is a marker of the autonomic nervous system, with elevated heart rate reflecting a shift in autonomic balance toward enhanced sympathetic nervous activity and reduced vagal tone (21). Some evidence suggests that sympathetic activation contributes to the development of insulin resistance in humans (7,8,22,23). A pilot study showed that 3 months after renal denervation, fasting glucose concentrations were reduced in patients with resistant hypertension, suggesting that the sympathetic nervous system may directly modulate the glucose metabolism (24).…”

Section: Discussionmentioning

confidence: 99%

“…Elevated heart rate has been associated with an increased risk of type 2 diabetes in a number of epidemiological studies (1,2,3,4,5). This association has been mainly attributed to increased insulin resistance, secondary to the activation of sympathetic nerve activity (6,7,8). However, only one small longitudinal study (7) has assessed the predictive value of sympathetic activity on the development of insulin resistance and fasting hyperglycaemia, using surrogate measures of insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

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Elevated heart rate predicts β cell function in non-diabetic individuals: the RISC cohort

Bonnet¹,

Empana²,

Natali³

et al. 2015

European Journal of Endocrinology

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Context: Elevated heart rate has been associated with insulin resistance and incident type 2 diabetes but its relationship with b-cell function is not known. Our aim was to investigate whether baseline heart rate is associated with b-cell function and hyperglycaemia. Methods: We used the prospective RISC cohort with 1005 non-diabetic individuals who had an oral glucose tolerance test (OGTT) at baseline and after 3 years. Impaired glucose regulation was defined as a fasting plasma glucose R6.1 mmol/l or a 2-h plasma glucose R7.8 mmol/l. Insulin sensitivity was assessed by the OGIS index and insulin secretion and b-cell glucose sensitivity at both baseline and 3 years. Results: Baseline heart rate was positively related to both fasting (P!0.0001) and 2 h glucose levels (PZ0.02) at year 3 and predicted the presence of impaired glucose regulation at year 3 in a logistic regression model adjusting for insulin sensitivity at inclusion (OR/10 beats per min: 1.31; 95% CI (1.07-1.61); PZ0.01). Baseline heart rate was associated with lower insulin sensitivity (bZK0.11; P!.0001), a decrease in both b-cell glucose sensitivity (bZK0.11; PZ0.003) and basal insulin secretion rate (bZK0.11; PZ0.002) at 3 years in an adjusted multivariable regression model. Baseline heart rate predicted the 3-year decrease in b-cell glucose sensitivity (bZK0.10; PZ0.007) and basal insulin secretion (bZK0.12; PZ0.007). Conclusions: Heart rate predicts b-cell function and impaired glucose regulation at 3 years in non-diabetic individuals, independently of the level of insulin sensitivity. These findings suggest a possible effect of the sympathetic nervous system on b-cell dysfunction, which deserves further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated heart rate predicts β cell function in non-diabetic individuals: the RISC cohort

Bonnet¹,

Empana²,

Natali³

et al. 2015

European Journal of Endocrinology

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“…insulin-mediated glucose uptake in skeletal muscle. 24 In non-dippers, the sympathetic tone is believed to be increased at night, suggesting that they have nocturnal autonomic dysfunction. 25 Obese patients have increased prevalence of non-dipping status, 26 and in this study, non-dippers had a higher BMI.…”

Section: Discussionmentioning

confidence: 99%

Non-dipping pattern in ambulatory blood pressure monitoring is associated with metabolic abnormalities in a random sample of middle-aged subjects

2009

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A reduction in the blood pressure decline at night (o10% from daytime systolic blood pressure (SBP)) during 24-h ambulatory blood pressure monitoring (ABPM) ('non-dipping pattern') is associated with cardiovascular morbidity. Our aim was to evaluate whether ABPM characteristics are associated with metabolic abnormalities in subjects without known hypertension or type 2 diabetes mellitus (T2DM). This is a cross-sectional population-based study on middle-aged subjects (n¼462). Two distinct definitions of metabolic syndrome (MetS) were used: National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International Diabetes Federation (IDF) criteria. Results suggested that subjects characterized by non-dipping in 24 h ABPM were more obese (P¼0.014). After adjustment for body mass index, age and sex, non-dippers had higher verylow-density lipoprotein (VLDL)-cholesterol (P¼0.003), total (P¼0.029)-and VLDL-triglycerides (P¼0.026) and oral glucose tolerance test 2 h blood glucose (P¼0.027) compared with dippers. Non-dipping status was more common among subjects with MetS (Pp0.01), impaired glucose tolerance (IGT) (Po0.05) and in those with the combination of IGT-T2DM (Pp0.01) than among those without these abnormalities. ABPM non-dipping status was an independent predictor of IGT in multivariate models (Po0.05). With respect to MetS components, high triglycerides (Pp0.005) and low high density lipoprotein-cholesterol (Po0.05) were associated with a non-dipping pattern. The percentage decline in blood pressure from day to night decreased with the number of metabolic abnormalities (P¼0.012). In conclusion, ABPM non-dipping status is an independent predictor of glucose intolerance. It is also associated with several other metabolic abnormalities. Whether non-dipping pattern is causally related to these metabolic aberrations remains to be explored in a future prospective follow-up of this cohort.

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“…Another possibility is that the cause of sympathetic hyperactivity in HT is insulin resistance because this frequent concomitant of a high-BP state leads to hyperinsulinemia, which is known to either increase sympathetic nerve traffic or to stimulate NE secretion from the sympathetic nerve endings, all effects being greater in subjects with HT. 27,28 It should be emphasized, however, that sympathetic activation has in turn been shown to cause insulin resistance, 29,30 so that it is still uncertain which of the 2 alterations precedes and determines the other. In a recent longitudinal study by Japanese investigators, an increase in plasma NE was seen years before the increase in plasma insulin levels also became manifest, 31 suggesting the derangement in glucose metabolism to follow rather than precede the sympathetic derangement.…”

Section: Mancia Et Al Sympathetic Overactivity In Hypertensionmentioning

confidence: 99%

Sympathetic Activation in the Pathogenesis of Hypertension and Progression of Organ Damage

et al. 1999

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Abstract-Although animal models of hypertension have clearly shown that high blood pressure is associated with and is probably caused by an increase in sympathetic cardiovascular influences, a similar demonstration in humans has been more difficult to obtain for methodological reasons. There is now evidence, however, of increased sympathetic activity in essential hypertension. This article will review this evidence by examining data showing that plasma norepinephrine is increased in essential hypertension and that this is also the case for systemic and regional norepinephrine spillover, as well as for the sympathetic nerve firing rate in the skeletal muscle nerve district. Evidence will also be provided that sympathetic activation is a peculiar feature of essential hypertension, particularly in its early stages, with secondary forms of high blood pressure not usually characterized by an increased central sympathetic outflow. Humoral, metabolic, reflex, and central mechanisms are likely to be the factors responsible for the adrenergic activation characterizing hypertension, which may also promote the development and progression of the cardiac and vascular alterations that lead to hypertension-related morbidity and mortality, independent of blood pressure values. This represents the rationale for considering sympathetic deactivation one of the major goals of antihypertensive treatment. Key Words: nervous system, sympathetic Ⅲ hypertension, essential Ⅲ hypertension, secondary Ⅲ pressoreceptors Ⅲ hypertrophy Ⅲ norepinephrine N eural adrenergic factors have long been hypothesized to be important in the initiation and maintenance of high blood pressure (BP). For a long time, however, the evidence supporting this hypothesis was largely limited to the results of studies performed in different animal models of hypertension (HT), in which an enhanced sympathetic drive to the heart and peripheral circulation was shown either to trigger a persistent BP elevation or to maintain the BP elevation originally induced by nonadrenergic mechanisms. [1][2][3][4] This picture has changed in the past 20 years or so because a variety of techniques that allow indirect or direct quantification of adrenergic cardiovascular influences have all provided evidence of an activation of the sympathetic nervous system (SNS) in human HT as well. This article will review the evidence that sympathetic activity is increased in essential HT and that this increase may have a pathogenetic role. It will also discuss 2 other issues, ie, (1) the mechanisms that lead to sympathetic hyperactivity in essential HT and (2) the role exerted by this hyperactivity in the progression of the cardiovascular alterations that may complicate the hypertensive state. Evidence for Sympathetic ActivationIn the past 30 years, several techniques designed to quantify sympathetic cardiovascular influences in humans have shown them to be increased in essential HT. More than 25 years ago, for example, Julius and coworkers 5 showed that the elevated resting heart rate values of bo...

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Acute noradrenergic activation induces insulin resistance in human skeletal muscle

Cited by 93 publications

References 30 publications

Elevated heart rate predicts β cell function in non-diabetic individuals: the RISC cohort

Elevated heart rate predicts β cell function in non-diabetic individuals: the RISC cohort

Non-dipping pattern in ambulatory blood pressure monitoring is associated with metabolic abnormalities in a random sample of middle-aged subjects

Sympathetic Activation in the Pathogenesis of Hypertension and Progression of Organ Damage

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