Melatonin improves insulin sensitivity independently of weight loss in old obese rats

Zanuto, Ricardo; Siqueira-Filho, Mário Alves de; Caperuto, Luciana C.; Bacurau, Reury Frank Pereira; Hirata, Emiko; Peliciari-Garcia, Rodrigo A.; Amaral, Fernanda Gaspar do; Marçal, Anderson Carlos; Ribeiro, Laiane Medeiros; Camporez, João Paulo; Carpinelli, Ângelo Rafael; Bordin, Silvana; Cipolla‐Neto, José; Carvalho, Carla Roberta de Oliveira

doi:10.1111/jpi.12056

Cited by 78 publications

(64 citation statements)

References 72 publications

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“…However, similar to metformin, melatonin can increase the activity of AMPK and potentially enhance insulin sensitivity in the liver [101]. Accordingly, in aged rats, chronic melatonin supplementation in drinking water for 8-12 weeks increased insulin sensitivity by more than twofold without changing hepatic insulin receptor expression, suggesting that these insulin-sensitising effects were mediated by target tissues outside of the liver [102].…”

Section: Sleep Disturbance Circadian Disruption and Altered Glucose mentioning

confidence: 99%

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: Sleep Disturbance Circadian Disruption and Altered Glucose mentioning

confidence: 99%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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“…Many studies have shown that melatonin has favorable effects on glucose homeostasis since it might increase glucose tolerance and improve insulin sensitivity in various animal models [32][33][34]. Melatonin administration has been shown to acutely decrease plasma insulin level and increase insulin sensitivity in rats [35].…”

Section: Discussionmentioning

confidence: 99%

Long-term melatonin administration improves glucose homeostasis and insulin resistance state in high-fat-diet fed rats

Wan

et al. 2013

Open Life Sciences

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Emerging evidence support an important role of reactive oxygen species in various forms of insulin resistance. It is identified that melatonin has antioxidant properties and prevents toxic effects of reactive oxygen species. In this study, we sought to assess the involvement of melatonin in the progression of insulin resistance in response to a high-fat diet (HFD) and to investigate the underlying mechanisms. Male rats were fed with a control diet, a high-fat diet, or a high-fat diet supplemented with melatonin (5 mg kg−1, i.p.) for 10 weeks. Glucose homeostasis, insulin sensitivity, antioxidative potency, and metabolic profiles in the rats were evaluated. Our results showed that a HFD led to increasing body mass, adipose tissue weight, plasma insulin, total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), and decreased HDL-cholesterol (HDL-C) in rats. There was also a significant increase in the level of malondialdehyde (MDA) and decrease in superoxide dismutase (SOD) activity, oxidative stress markers both in the plasma and liver. An enhanced hepatic phosphoenolpyruvate carboxy-kinase (PEPCK) activity and RNA expression were observed. Impaired insulin signaling was evidenced by reducing insulin receptor substrate 2 (IRS2) tyrosine phosphorylation and protein kinase B (PKB) serine phosphorylation in response to insulin. Overactivation of stress-activated protein kinases JNK was also observed in the liver of HFD rats. However, simultaneous administration of melatonin to HFD rats significantly reduced oxidative stress in the system and liver, markedly improved impaired glucose homeostasis, insulin sensitivity, antioxidative potency, metabolic profiles and all the aforesaid adverse changes in HFD rats. Our results demonstrated that anti-oxidative property of melatonin is sufficient to ameliorate the insulin resistance condition, leading to the improvement of glucose homeostasis and the restoration of hepatic insulin signaling in a rat model of HFD-induced insulin resistance.

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“…Melatonin is a hormone which is closely related to the regulation of insulin secretion and glucose/lipid metabolism. Melatonin showed positive impacts on metabolic syndrome due to its anti-hyperlipidemic effect and it is reported to reduce adiposity and body weight in animal studies (Chan & Tang, 1995;Srinivasan et al, 2013;Zanuto et al, 2013). Moreover, melatonin was showed to increase insulin sensitivity and glucose tolerance in rats fed with high fat or sucrose diets (Srinivasan et al, 2013).…”

Section: Discussionmentioning

confidence: 99%