NEU-P11, a novel melatonin agonist, inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats

She, Meihua; Deng, Xin; Guo, Zhenyu; Laudon, Moshe; Hu, Zhuowei; Liao, Duan‐Fang; Hu, Xiaobo; Luo, Yang; Shen, Qingyun; Su, Zehong; Yin, Wang

doi:10.1016/j.phrs.2009.01.005

Cited by 99 publications

(95 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While piromelatine may positively affect both insulin resistance and lipid metabolism in rodent models of type 2 diabetes [128,162], these findings have not yet been confirmed in a controlled clinical trial. Thus, it remains to be elucidated whether melatonin or melatonin receptor agonists can be used clinically as an effective means for improving glycaemic control and normalising sleep patterns among type 2 diabetic patients, or perhaps as a preventative treatment to halt the progression of metabolic disease.…”

Section: Clinical Evidencementioning

confidence: 92%

“…Accordingly, treatment of DIO rats with melatonin attenuated weight gain and reduced glucose, leptin and triacylglycerol levels [127]. Daily injection of DIO rats with melatonin or the melatonin agonist Neu-P11 (piromelatine) also inhibited weight gain and improved insulin sensitivity, in effect countering the negative influence of DIO [128]. Finally, Sartori and colleagues reported a significant improvement in glucose tolerance in DIO mice treated with melatonin for 8 weeks [129].…”

Section: The Pancreatic Response To Melatoninmentioning

confidence: 97%

“…However, to target the melatonin signalling pathway with greater efficiency, several long-lasting high affinity MT1/MT2 receptor agonists have been developed [155][156][157][158]. These drugs, including tasimelteon (Hetlioz; [159]), ramelteon (Rozerem; [160]) and piromelatine (Neu-P11; [128]), are highly potent and selective agonists. Additionally, the compound IIK7 has been developed as a melatonin receptor agonist with 90-fold higher affinity for the MT2 receptor [161].…”

Section: Clinical Evidencementioning

confidence: 99%

See 2 more Smart Citations

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: 92%

Section: The Pancreatic Response To Melatoninmentioning

confidence: 97%

Section: Clinical Evidencementioning

confidence: 99%

See 1 more Smart Citation

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Neu-P11 [38] , a novel melatonin agonist, is currently in development for the treatment of insomnia. Neu-P11 binds with high affinity to melatonin receptors and exerts GABA enhancing properties [39] .…”

Section: Introductionmentioning

confidence: 99%

“…Neu-P11 binds with high affinity to melatonin receptors and exerts GABA enhancing properties [39] . Recent studies have shown that Neu-P11 promoted sleep [39] , inhibited weight gain and improved insulin sensitivity in high-fat/high-sucrose-fed rats [38] . In the present study we investigated the potential effects of Neu-P11 in two models of depression in rats and one model of anxiety in mice.…”

Section: Introductionmentioning

confidence: 99%

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

et al. 2010

Self Cite

View full text Add to dashboard Cite

Aim: To investigate the potential antidepressant and anxiolytic effects of Neu-P11, a novel melatonin agonist, in two models of depression in rats and a model of anxiety in mice. Methods: In the learned helplessness test (LH), Neu-P11 or melatonin (25-100 mg/kg, ip) was administered to rats 2 h before the beginning of the dark phase once a day for 5 days and the number of escape failures and intertrial crossings during the test phase were recorded. In the forced swimming test (FST), rats received a single or repeated administration of Neu-P11 (25-100 mg/kg, ip). The total period of immobility during the test phase was assessed. In the elevated plus-maze test (EPM), mice were treated with Neu-P11 (25-100 mg/kg, ip) or melatonin in the morning or in the evening and tested 2 h later. The percentage of time spent in the open arms and the open arms entries were assessed. Results: In the LH test, Neu-P11 but not melatonin significantly decreased the escape deficit and had no effect on the intertrial crossings. In the FST, a single or repeated administration of Neu-P11, either in the morning or in the evening, significantly decreased the duration of immobility. In the EPM test, Neu-P11 significantly increased the percentage of time spent in the open arms and the open arms entries irrespective to the time of administration. Melatonin was effective only when administered in the afternoon. Conclusion:The results demonstrate that Neu-P11 exerts antidepressant and anxiolytic activities in rodent models.

show abstract

Effect of chromium picolinate and melatonin either in single or in a combination in high carbohydrate diet‐fed male Wistar rats

2015

View full text Add to dashboard Cite

This study is designed to know the effects of chromium picolinate (CrPic) and melatonin (Mel) each alone and in a combination on high carbohydrate diet‐fed (HCD‐fed) male Wistar rats that exhibit insulin resistance (IR), hyperglycemia, and oxidative stress. Wistar rats have been categorized into five groups. Each group consisted of six male Wistar rats, control rats (group I), HCD (group II), HCD + CrPic (group III), HCD + Mel (group IV), and HCD + CrPic + Mel (group V). Insignificant differences were observed in serum levels of superoxide dismutase, nitric oxide, and zinc in group III, group IV, and group V when each group was compared with group II rats respectively. Significant differences were observed in group III, group IV, and group V when each group was compared with group II in homeostasis model assessment‐estimated IR (P < 0.05, <0.0.05, <0.05), and in the levels of blood glucose (P < 0.05, <0.0.05, <0.05), total cholesterol (P < 0.05, <0.001, <0.001), triacylglycerols (<0.05, <0.001, <0.001), high density lipoprotein cholesterol (P < 0.05, <0.001, <0.001), malondialdehyde (P < 0.05, <0.05, <0.001), catalase (P <0.05, <0.05, <0.05), glutathione (P < 0.05, <0.05, <0.05), Mel (P < 0.05, <0.05, <0.001), and copper (P < 0.05, <0.05, < 0.001). In view of these results, HCD‐fed male Wistar rats that are destined to attain IR and T2DM through diet can be prevented by giving CrPic and Mel administration in alone or in a combination. © 2015 BioFactors, 42(1):106–114, 2016

show abstract

NEU-P11, a novel melatonin agonist, inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats

Cited by 99 publications

References 36 publications

Chronomedicine and type 2 diabetes: shining some light on melatonin

Chronomedicine and type 2 diabetes: shining some light on melatonin

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

Effect of chromium picolinate and melatonin either in single or in a combination in high carbohydrate diet‐fed male Wistar rats

Contact Info

Product

Resources

About