Epinephrine and the Metabolic Syndrome

Abstract

Epinephrine is the prototypical stress hormone. Its stimulation of all α and β adrenergic receptors elicits short-term systolic hypertension, hyperglycemia, and other aspects of the metabolic syndrome. Acute epinephrine infusion increases cardiac output and induces insulin resistance, but removal of the adrenal medulla has no consistent effect on blood pressure. Epinephrine is the most effective endogenous agonist at the β2 receptor. Transgenic mice that cannot make epinephrine and mice that lack the β2 receptor become hypertensive during exercise, presumably owing to the absence of β2-mediated vasodilatation. Epinephrine-deficient mice also have cardiac remodeling and poor cardiac responses to stress, but do not develop resting hypertension. Mice that cannot make epinephrine have a normal metabolism on a regular 14% fat diet but become hyperglycemic and insulin resistant when they eat a high fat diet. Vigorous exercise prevents diabetes in young mice and humans that overeat. However, exercise is a less effective treatment in older type 2 human diabetics and had no effect on glucose or insulin responses in older, diabetic mice. Sensitivity of the β2 receptor falls sharply with advancing age, and adrenal epinephrine release also decreases. However, treatment of older diabetic mice with a β2 adrenergic agonist improved insulin sensitivity, indicating that β2 subsensitivity can be overcome pharmacologically. Recent studies show that over the long term, epinephrine prevents hypertension during stress and improves glucose tolerance. The hyperglycemic influence of epinephrine is short-lived. Chronic administration of epinephrine and other β2 agonists improves cellular glucose uptake and metabolism. Overall, epinephrine counteracts the metabolic syndrome.

Green Tea and Vitamin E Enhance Exercise-Induced Benefits in Body Composition, Glucose Homeostasis, and Antioxidant Status in Elderly Men and Women

“…Improved glucose homeostasis in the GTVE group may be associated with green tea activation of the SNS. With aging, the sensitivity of β 2 -adrenergic receptors declines; as a consequence, exercise may fail to lower blood glucose levels as demonstrated in old obese mice, where β 2 agonists were able to lower blood glucose [41]. It is possible that in our study exercise levels were not enough to lower blood glucose levels because of the age limitations of the participants; however, green tea as an SNS activator along with exercise made a reduction of blood glucose possible.…”

Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice

“…Indeed, it has been suggested that ChE inhibitors exacerbate this ACh-induced catecholamine release (Akiyama et al, 2003), which could trigger transient hyperglycemia by decreasing insulin-stimulated translocation of glucose transporters to the plasma membrane (Mulder et al, 2005). Ultimately, the excessive release of catecholamines could lead to insulin resistance (Ziegler et al, 2012).…”

METABOLIC PHENOTYPING GUIDELINES: Assessing glucose homeostasis in rodent models

“…It is important to minimise stress to the experimental animal in all in vivo studies of glucose homeostasis because it is well established that activating the stress response, with the subsequent elevations in adrenaline and noradrenaline, has major physiological effects on glucose handling (Nonogaki 2000, Ziegler et al 2012, which will complicate the interpretation of the experimental data. This is particularly relevant in protocols that involve restraint or repeated handling of the animal, which are acknowledged stressful stimuli (Balcombe et al 2004, Buynitsky & Mostofsky 2009).…”