Daily Rhythms of Plasma Melatonin, but Not Plasma Leptin or Leptin mRNA, Vary between Lean, Obese and Type 2 Diabetic Men

Mäntele, Simone; Otway, Daniella; Middleton, Benita; Bretschneider, Silvia; Wright, John W.; Robertson, M. Denise; Skene, Debra J.; Johnston, Jeanne D.

doi:10.1371/journal.pone.0037123

Cited by 88 publications

(79 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Though considerable evidence supports a positive correlation between lower night-time melatonin and increased risk of type 2 diabetes [50,139], not all data fully support this claim. Mantele and colleagues demonstrated that night-time melatonin levels were, in fact, elevated in obese individuals (compared with lean non-diabetic individuals) and unaffected in type 2 diabetic participants [150]. However, in the same study they determined that melatonin levels were suppressed in individuals with type 2 diabetes when compared with weight-matched obese non-diabetic participants [150].…”

Section: Clinical Evidencementioning

confidence: 99%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

View full text Add to dashboard Cite

In mammals, the circadian timing system drives rhythms of physiology and behaviour, including the daily rhythms of feeding and activity. The timing system coordinates temporal variation in the biochemical landscape with changes in nutrient intake in order to optimise energy balance and maintain metabolic homeostasis. Circadian disruption (e.g. as a result of shift work or jet lag) can disturb this continuity and increase the risk of cardiometabolic disease. Obesity and metabolic disease can also disturb the timing and amplitude of the clock in multiple organ systems, further exacerbating disease progression. As our understanding of the synergy between the timing system and metabolism has grown, an interest has emerged in the development of novel clock-targeting pharmaceuticals or nutraceuticals for the treatment of metabolic dysfunction. Recently, the pineal hormone melatonin has received some attention as a potential chronotherapeutic drug for metabolic disease. Melatonin is well known for its sleep-promoting effects and putative activity as a chronobiotic drug, stimulating coordination of biochemical oscillations through targeting the internal timing system. Melatonin affects the insulin secretory activity of the pancreatic beta cell, hepatic glucose metabolism and insulin sensitivity. Individuals with type 2 diabetes mellitus have lower night-time serum melatonin levels and increased risk of comorbid sleep disturbances compared with healthy individuals. Further, reduced melatonin levels, and mutations and/or genetic polymorphisms of the melatonin receptors are associated with an increased risk of developing type 2 diabetes. Herein we review our understanding of molecular clock control of glucose homeostasis, detail the influence of circadian disruption on glucose metabolism in critical peripheral tissues, explore the contribution of melatonin signalling to the aetiology of type 2 diabetes, and discuss the pros and cons of melatonin chronopharmacotherapy in disease management.

show abstract

Section: Clinical Evidencementioning

confidence: 99%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

View full text Add to dashboard Cite

show abstract

“…For instance, recent studies suggested that a disruption in rhythmic melatonin production is relevant to the etiology of diabetes. Nocturnal melatonin levels were reported to be significantly reduced in obese patients with type 2 diabetes compared with weight-matched controls (20). Reduced nocturnal melatonin secretion was also reported to correlate with increased gluconeogenesis during the first hours of the morning in patients with type 2 diabetes (29).…”

Section: Discussionmentioning

confidence: 99%

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Faria

Kinote

Ignácio-Souza

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Melatonin can contribute to glucose homeostasis either by decreasing gluconeogenesis or by counteracting insulin resistance in distinct models of obesity. However, the precise mechanism through which melatonin controls glucose homeostasis is not completely understood. Male Wistar rats were administered an intracerebroventricular (icv) injection of melatonin and one of following: an icv injection of a phosphatidylinositol 3-kinase (PI3K) inhibitor, an icv injection of a melatonin receptor (MT) antagonist, or an intraperitoneal (ip) injection of a muscarinic receptor antagonist. Anesthetized rats were subjected to pyruvate tolerance test to estimate in vivo glucose clearance after pyruvate load and in situ liver perfusion to assess hepatic gluconeogenesis. The hypothalamus was removed to determine Akt phosphorylation. Melatonin injections in the central nervous system suppressed hepatic gluconeogenesis and increased hypothalamic Akt phosphorylation. These effects of melatonin were suppressed either by icv injections of PI3K inhibitors and MT antagonists and by ip injection of a muscarinic receptor antagonist. We conclude that melatonin activates hypothalamus-liver communication that may contribute to circadian adjustments of gluconeogenesis. These data further suggest a physiopathological relationship between the circadian disruptions in metabolism and reduced levels of melatonin found in type 2 diabetes patients. melatonin; gluconeogenesis; melatonin receptors; liver MELATONIN (5-methoxy-N-acetyltryptamine) is produced and secreted by the pineal gland in a circadian fashion, with peak levels during the dark phase of the light-dark cycle. The canonical function of melatonin is to transmit environmental information (i.e., the length of the dark period) to the living organism, thereby synchronizing the circadian clock in the hypothalamic suprachiasmatic nucleus (22). In vivo and in vitro experiments have demonstrated that melatonin also plays a role in energy homeostasis by regulating body mass and adiposity and leptin expression by adipocytes (1, 40). Glucose homeostasis is also altered by the absence of melatonin in such a way that pinealectomized rats display glucose intolerance and desynchronized circadian pattern of gluconeogenesis, hallmarked by increased nighttime glucose levels (17,18,23). Moreover, chronic melatonin administration has been shown to improve glucose homeostasis not only in pinealectomized rats but also in rats rendered insulin resistant by diet manipulation (16,33,34).Although it has been demonstrated that melatonin stimulates glucose uptake in adipocytes and skeletal muscle cells in vitro (10, 19), the precise mechanism by which this hormone reduces whole body glucose intolerance has not been determined precisely. In mammals, the effects of melatonin are mediated in part by specific high-affinity G protein-coupled receptors known as melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) (31). We have demonstrated previously that melatonin acts locally in the hypothalamus to activate the p...

show abstract

“…In recent years, considerable interest has focused on the potential disruptive effects of disease and disease states on sleep-wake cycles and circadian organisation, though few systematic studies have been undertaken (Gamble et al, 2014;Mäntele et al, 2012;Maury et al, 2014;Montagnese et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Assessment of 6-sulfatoxymelatonin rhythms and melatonin response to light in disease states: Lessons from cirrhosis

Montagnese¹,

Middleton²,

Corrias³

et al. 2014

Chronobiology International

Self Cite

View full text Add to dashboard Cite

Circadian rhythmicity and non-visual sensitivity to light can be assessed, in healthy subjects, by measuring the rhythm of the urinary melatonin metabolite 6-sulphatoxymelatonin (aMT6s) and by determining the response of plasma melatonin to nocturnal retinal light exposure, respectively. However, the validity of these techniques has not been assessed in disease states in which disruption of the circadian rhythm is known or suspected to occur. Thus, the aims of this study were as follows: (i) to assess the reliability of circadian aMT6s profile estimates derived from 36 h versus 56 h urine collections and (ii) to test different models for calculating melatonin suppression in response to light in healthy volunteers and patients with cirrhosis. Twenty patients with biopsy-proven cirrhosis and 10 matched healthy volunteers undertook: (i) separate 36 - and 56-h urine collections, under controlled conditions, for cosinor analysis of the urinary aMT6s profile; (ii) a melatonin suppression test, comprising of a baseline night, during which subjects were woken and asked to sit in front of a switched off light sphere, and an experimental night, identically executed, except that the light sphere was switched on and the subjects were exposed to white light (4.1 × 10(14) photons/cm(2)/s) for 30 min. Alternative approaches to the calculation of melatonin suppression were taken, with/without inclusion of the baseline night. Eighteen patients and eight healthy volunteers had matched analysable 36 - and 56-h urinary samples. Cosinor analysis showed a significant fit in 88% of the remaining 56 h collections, and 48% of the remaining 36-h collections. Thus, eight patients and five healthy volunteers had matched analysable samples for cosinor analysis. In the healthy volunteers, aMT6s profile indices obtained using the 36 - and the 56-h collections did not differ significantly. In contrast, considerably more variability was observed in patients [i.e. the difference in the aMT6s peak time was 0.5 ± 1.7 h (limits of agreement: -3.9; +2.9 h)]. No difficulties were encountered in obtaining suppression estimates by use of the experimental night only. In contrast, suppression estimates obtained by use of both nights were considered inaccurate in one (11%) healthy volunteer and in 5 (28%) patients, primarily because: (i) melatonin concentrations at the beginning of light administration were significantly different on baseline and experimental night; (ii) the rise in melatonin was inconsistent on baseline night; and (iii) the shape of the rising phase of melatonin was different on baseline and experimental night. In conclusion, shorter urine collections lead to a higher number of profiles with no significant cosinor fit, and differences in cosinor indices obtained from the 36 - and 56-h collections were considerable, especially in patients. Thus, 56-h collections are probably advisable. Use of both baseline and experimental nights to calculate melatonin suppression often resulted in increased variation and confounding, due to point oscillat...

show abstract

Daily Rhythms of Plasma Melatonin, but Not Plasma Leptin or Leptin mRNA, Vary between Lean, Obese and Type 2 Diabetic Men

Cited by 88 publications

References 40 publications

Chronomedicine and type 2 diabetes: shining some light on melatonin

Chronomedicine and type 2 diabetes: shining some light on melatonin

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Assessment of 6-sulfatoxymelatonin rhythms and melatonin response to light in disease states: Lessons from cirrhosis

Contact Info

Product

Resources

About