Acute Melatonin Administration in Humans Impairs Glucose Tolerance in Both the Morning and Evening

Rubio-Sastre, Patricia; Scheer, Frank A.J.L.; Gómez-Abellán, Purificación; Madrid, Juan Antonio; Garaulet, Marta

doi:10.5665/sleep.4088

Cited by 150 publications

(130 citation statements)

References 25 publications

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“…Moreover, recent randomised controlled trials suggest that chronic treatment with melatonin in combination with oral blood glucose lowering agents improves fasting and postprandial glycaemic control and reduces HbA 1c levels [152,154]. Contrary to these studies, reports show that melatonin can actually impair glucose tolerance in young healthy individuals [28,29]. These studies suggest that melatonin may be detrimental for glycaemic control and potentially advance the onset of type 2 diabetes.…”

Section: Clinical Evidencecontrasting

confidence: 43%

“…This temporal relationship presents a unique challenge to understanding the mechanisms whereby melatonin affects glucose metabolism. In addition to this dichotomy, we find that melatonin can have conflicting impacts on target tissues, such as the pancreatic beta cell, in both rodents and humans [49,111,140], and highly variable effects on systemic glucose homeostasis and insulin sensitivity [28,29,111,141,142]. In vitro, melatonin inhibits insulin secretion by lowering cAMP and cGMP production [27,49,[143][144][145].…”

Section: The Pancreatic Response To Melatoninmentioning

confidence: 99%

“…Importantly, carriers of this variant also displayed impaired glucose tolerance following an acute exposure to melatonin [28].…”

Section: Therapeutic Agentsmentioning

confidence: 99%

“…Recent clinical studies have determined that melatonin can exert a marked influence on glycaemic control [28,29]. Melatonin falls into a special class of compounds, referred to as chronobiotics, that can simultaneously affect both the timing system and metabolism, possibly via direct influence on the molecular clock [30][31][32].…”

Section: The Internal Timing System and Metabolic Dysfunctionmentioning

confidence: 99%

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Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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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.

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Section: Clinical Evidencecontrasting

confidence: 43%

Section: The Pancreatic Response To Melatoninmentioning

confidence: 99%

“…Importantly, carriers of this variant also displayed impaired glucose tolerance following an acute exposure to melatonin [28].…”

Section: Therapeutic Agentsmentioning

confidence: 99%

Section: The Internal Timing System and Metabolic Dysfunctionmentioning

confidence: 99%

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Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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“…On this basis melatonin may perhaps be involved in the genesis of diabetes (6). In humans, melatonin administration reduced glucose tolerance mainly by decreasing insulin release at the time of morning while decline in insulin sensitivity was observed in the evening (87). In addition, various studies established a correlation between sleep disorders and a greater risk for a decreased glucose tolerance and type 2 diabetes (88)(89)(90).…”

Section: Melatonin and Diabetesmentioning

confidence: 99%

The role of melatonin in diabetes: therapeutic implications

Sharma

Singh

Ahmad

et al. 2015

Arch. Endocrinol. Metab.

110

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Melatonin referred as the hormone of darkness is mainly secreted by pineal gland, its levels being elevated during night and low during the day. The effects of melatonin on insulin secretion are mediated through the melatonin receptors (MT1 and MT2). It decreases insulin secretion by inhibiting cAMP and cGMP pathways but activates the phospholipaseC/IP3 pathway, which mobilizes Ca 2+ from organelles and, consequently increases insulin secretion. Both in vivo and in vitro, insulin secretion by the pancreatic islets in a circadian manner, is due to the melatonin action on the melatonin receptors inducing a phase shift in the cells. Melatonin may be involved in the genesis of diabetes as a reduction in melatonin levels and a functional interrelationship between melatonin and insulin was observed in diabetic patients. Evidences from experimental studies proved that melatonin induces production of insulin growth factor and promotes insulin receptor tyrosine phosphorylation. The disturbance of internal circadian system induces glucose intolerance and insulin resistance, which could be restored by melatonin supplementation. Therefore, the presence of melatonin receptors on human pancreatic islets may have an impact on pharmacotherapy of type 2 diabetes. Arch Endocrinol Metab.2015;59(5):391-9

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The Circadian Timing System and Endocrine Physiology

Sellix

2016

Circadian Clocks: Role in Health and Disease

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Acute Melatonin Administration in Humans Impairs Glucose Tolerance in Both the Morning and Evening

Abstract: Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. When administering melatonin, the proximity to meal timing may need to be considered, particularly in those at risk for glucose intolerance.

Cited by 150 publications

References 25 publications

Chronomedicine and type 2 diabetes: shining some light on melatonin

Chronomedicine and type 2 diabetes: shining some light on melatonin

The role of melatonin in diabetes: therapeutic implications

The Circadian Timing System and Endocrine Physiology

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