Diabetes mellitus and melatonin: Where are we?

Patel, Roma; Parmar, Nishant; Palit, Sayantani Pramanik; Rathwa, Nirali; Ramachandran, A. V.; Begum, Rasheedunnisa

doi:10.1016/j.biochi.2022.01.001

Cited by 27 publications

(13 citation statements)

References 159 publications

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“…In addition, melatonin is a pleiotropic molecule regulating biorhythm and sleep, and its effects on body metabolism are diverse and complex. In this study, in vitro and in vivo research of melatonin focused on its beneficial effects on steroidogenesis by targeting diabetic manifestations such as mitochondrial dysfunction and oxidative stress, but many other questions, such as the appropriate dosage and timing of melatonin intake to optimize the effect of melatonin, still need to be considered in terms of its clinical application [18].…”

Section: Discussionmentioning

confidence: 99%

“…Exogenous melatonin treatment in cell lines, rodent models, and diabetic patients has shown a potent effect in alleviating DM-related complications, such as diabetic cardiovascular disorders, neuropathy, retinopathy, and nephropathy [18]. In addition, melatonin is closely associated with male reproductive function, especially in the testis, because melatonin receptor is expressed in testicular cells and Leydig cells are sensitive to melatonin [19].…”

Section: Introductionmentioning

confidence: 99%

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Melatonin ameliorates diabetic hyperglycaemia-induced impairment of Leydig cell steroidogenic function through activation of SIRT1 pathway

Wang

Zhang

Lin

et al. 2022

Reprod Biol Endocrinol

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Background Diabetes mellitus (DM)-related complications are important health problems worldwide. The underlying mechanisms for diabetic male subfertility/infertility are considerably complicated and need to be unveiled for therapeutic intervention. Melatonin treatment was investigated to assess the beneficial effects on injured steroidogenic function in DM due to its regulatory roles in mitochondria and autophagy. Methods Diabetic hyperglycaemia was induced in rats injected with streptozotocin (STZ, 55 mg/kg/d) or simulated in TM3 Leydig cell line cultured with medium containing 30 mM D-glucose. Then, diabetic rats or the TM3 cells under high glucose were treated with melatonin. The diabetic rats were randomly divided into diabetes mellitus group (DM group), insulin treatment group (DM + INS group) and melatonin treatment group (DM + MT group). The TM3 Leydig cells were divided into a normal glucose control group (NG group), a high glucose treatment group (HG group), and a melatonin treatment group (HG + MT group). Then, Sirt1 (silent mating type information regulation 2 homologue) 1 expression was knocked down by siRNA. Results The results showed that hyperglycaemia induced a decline in steroidogenesis, accompanied by autophagy defects, mitochondrial dysfunction and oxidative stress, in rats in the DM group or TM3 Leydig cells in the HG group. Furthermore, reduced SIRT1 expression levels and hyperacetylation were found in Leydig cells of DM group. Melatonin treatment ameliorated hyperglycaemia-induced impairment of Leydig cell function with simultaneous stimulation of 5’-adenosine monophosphate activated protein kinase (AMPK)/SIRT1 activity and the expression of autophagy-related genes. With regards to mitochondrial function, it promoted mitochondrial biogenesis with elevated PGC-1α, NRF1 and mtTFA, improved mitochondrial morphology, increased BNIP3L-related mitophagy and alleviated oxidative stress. Further results revealed that knockdown of Sirt1 in Leydig cells prevented the protective effects provided by melatonin against high glucose treatment, and interestingly, neutralization of reactive oxygen species (ROS) by N-acetyl-L-cysteine pretreatment abolished the stimulatory effect of melatonin on AMPK/SIRT1 activity in Leydig cells and prevented the induction of autophagy and mitochondrial biogenesis in the context of high glucose, indicating that modulation of SIRT1 pathway by melatonin was closely linked to ROS levels and oxidative stress. Conclusions These findings suggest that SIRT1 pathway plays essential roles in the pleiotropic actions of melatonin on Leydig cells and in the prevention of hyperglycaemia-induced steroidogenic dysfunction. The stimulatory action of melatonin on SIRT1 pathway is related to oxidative stress and its antioxidant property. Our data provide new evidence for the relationship of melatonin and SIRT1 pathway in the context of hyperglycaemia, and melatonin as a combination therapy may be useful to combat DM-related complications, especially male reproductive system injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melatonin ameliorates diabetic hyperglycaemia-induced impairment of Leydig cell steroidogenic function through activation of SIRT1 pathway

Wang

Zhang

Lin

et al. 2022

Reprod Biol Endocrinol

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“…This consequently causes an inhibition of melatonin binding and information transmission. This is ultimately associated with a higher risk of type 2 diabetes mellitus [ 155 , 156 , 157 , 159 , 160 , 161 ]. A reduced level of melatonin is also implicated in the pathogenesis of type 2 diabetes [ 160 , 161 ].…”

Section: The Role Of Melatonin In Kidney Diseasesmentioning

confidence: 99%

“…This is ultimately associated with a higher risk of type 2 diabetes mellitus [ 155 , 156 , 157 , 159 , 160 , 161 ]. A reduced level of melatonin is also implicated in the pathogenesis of type 2 diabetes [ 160 , 161 ]. A study by Mok that included numerous clinical trials with the use of melatonin supplementation in patients with diabetes proved that melatonin administration may be a new therapeutic method to improve the diabetic condition and reduce the prevalence of diabetic complications [ 159 , 161 ].…”

Section: The Role Of Melatonin In Kidney Diseasesmentioning

confidence: 99%

Melatonin Treatment in Kidney Diseases

Markowska

Niemczyk

Romejko

2023

Cells

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Melatonin is a neurohormone that is mainly secreted by the pineal gland. It coordinates the work of the superior biological clock and consequently affects many processes in the human body. Disorders of the waking and sleeping period result in nervous system imbalance and generate metabolic and endocrine derangements. The purpose of this review is to provide information regarding the potential benefits of melatonin use, particularly in kidney diseases. The impact on the cardiovascular system, diabetes, and homeostasis causes melatonin to be indirectly connected to kidney function and quality of life in people with chronic kidney disease. Moreover, there are numerous reports showing that melatonin plays a role as an antioxidant, free radical scavenger, and cytoprotective agent. This means that the supplementation of melatonin can be helpful in almost every type of kidney injury because inflammation, apoptosis, and oxidative stress occur, regardless of the mechanism. The administration of melatonin has a renoprotective effect and inhibits the progression of complications connected to renal failure. It is very important that exogenous melatonin supplementation is well tolerated and that the number of side effects caused by this type of treatment is low.

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“…According to the latest estimates of the International Diabetes Federation Diabetes Atlas, the number of people with DM will exceed 450 million worldwide, which is also expected to reach 693 million by 2045 (Cho et al, 2018). DM and diabetes-related complications are amongst the leading causes of mortality worldwide (Patel et al, 2022). DM has more than 100 kinds of complications, which has the most known complications of diseases.…”

Section: Introductionmentioning

confidence: 99%

Roxadustat, a HIF-PHD inhibitor with exploitable potential on diabetes-related complications

Fang

Ma²,

Zhang³

et al. 2023

Front. Pharmacol.

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Diabetes mellitus (DM) is a group of metabolic diseases caused by absolute or relative deficiency of insulin secretion and characterized by chronic hyperglycemia. Its complications affect almost every tissue of the body, usually leading to blindness, renal failure, amputation, etc. and in the final stage, it mostly develops into cardiac failure, which is the main reason why diabetes mellitus manifests itself as a high clinical lethality. The pathogenesis of diabetes mellitus and its complications involves various pathological processes including excessive production of mitochondrial reactive oxygen species (ROS) and metabolic imbalance. Hypoxia-inducible Factor (HIF) signaling pathway plays an important role in both of the above processes. Roxadustat is an activator of Hypoxia-inducible Factor-1α, which increases the transcriptional activity of Hypoxia-inducible Factor-1α by inhibiting hypoxia-inducible factor prolyl hydroxylase (HIF-PHD). Roxadustat showed regulatory effects on maintaining metabolic stability in the hypoxic state of the body by activating many downstream signaling pathways such as vascular endothelial growth factor (VEGF), glucose transporter protein-1 (GLUT1), lactate dehydrogenase (LDHA), etc. This review summarizes the current research findings of roxadustat on the diseases of cardiomyopathy, nephropathy, retinal damage and impaired wound healing, which also occur at different stages of diabetes and greatly contribute to the damage caused by diabetes to the organism. We attempts to uncover a more comprehensive picture of the therapeutic effects of roxadustat, and inform its expanding research about diabetic complications treatment.

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Diabetes mellitus and melatonin: Where are we?

Cited by 27 publications

References 159 publications

Melatonin ameliorates diabetic hyperglycaemia-induced impairment of Leydig cell steroidogenic function through activation of SIRT1 pathway

Melatonin ameliorates diabetic hyperglycaemia-induced impairment of Leydig cell steroidogenic function through activation of SIRT1 pathway

Melatonin Treatment in Kidney Diseases

Roxadustat, a HIF-PHD inhibitor with exploitable potential on diabetes-related complications

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