Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function

Hajam, Younis Ahmad; Rai, Seema; Pandi‐Perumal, Seithikurippu R.; Brown, Gregory M.; Reíter, Russel J.; Cardinali, Daniel P.

doi:10.1159/000520280

Cited by 14 publications

(9 citation statements)

References 65 publications

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“…A large number of literature suggest a correlation between disturbed sleep orders and decreased glucose tolerance and T2D (Donga et al 2010 ; Yaggi et al 2006 ). A study reported by Hajam et al ( 2022 ) has reported the therapeutic efficacy of coadministration of insulin and melatonin rat models with diabetes-induced renal injury. The outcome of the study reported has revealed that the combination of insulin and melatonin may be quite effective to treat renal alterations caused by diabetes as confirmed by sera biochemical parameters, anti-inflammatory molecules in serum, and histoarchitecture changes in kidney (Hajam et al 2022 ).…”

Section: Melatonin and Diabetesmentioning

confidence: 99%

“…A study reported by Hajam et al ( 2022 ) has reported the therapeutic efficacy of coadministration of insulin and melatonin rat models with diabetes-induced renal injury. The outcome of the study reported has revealed that the combination of insulin and melatonin may be quite effective to treat renal alterations caused by diabetes as confirmed by sera biochemical parameters, anti-inflammatory molecules in serum, and histoarchitecture changes in kidney (Hajam et al 2022 ). The melatonin administration modulates the synthesis of insulin in the pancreatic β-cells as well as enhancing the optimistic insulin effect (Hajam and Rai 2019 ).…”

Section: Melatonin and Diabetesmentioning

confidence: 99%

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Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders

et al. 2023

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Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin production and to lesser extent by retina, lymphocytes, bone marrow, gastrointestinal tract, and thymus. Melatonin as a neurohormone is released into circulation wherein it penetrates all tissues of the body. Melatonin synthesis and secretion is supressed by light and enhanced by dark. Melatonin mostly exerts its effect through different pathways with melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) being the predominant type of receptor that are mainly expressed by many mammalian organs. Melatonin helps to regulate sleep patterns and circadian rhythms. In addition, melatonin acts as an antioxidant and scavenges excessive free radicals generated in the body by anti-excitatory and anti-inflammatory properties. A multiple array of other functions are displayed by melatonin that include oncostatic, hypnotic, immune regulation, reproduction, puberty timing, mood disorders, and transplantation. Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there. In the past century, a growing interest has been developed regarding the wide use of melatonin in treating various diseases like inflammatory, gastrointestinal, cancer, mood disorders, and others. Several melatonin agonists have been synthesized and are widely used in disease treatment. In this review, an effort has been made to describe the biochemistry of melatonin along with its therapeutic potential in various diseases of humans. Graphical Abstract

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Section: Melatonin and Diabetesmentioning

confidence: 99%

Section: Melatonin and Diabetesmentioning

confidence: 99%

Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders

et al. 2023

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“…A plethora of preclinical studies indicate the utility of melatonin in attenuating many of the consequences of T1DM, including the following: cardiovascular disorders [ 181 ], pancreatic β-cell regeneration [ 109 ], renal impairment [ 182 ], bone loss [ 183 ], cognitive deficits [ 110 ], erectile dysfunction [ 184 ], and body temperature circadian rhythm [ 185 ]. This is supported by clinical data showing lower melatonin levels in T1DM children [ 186 ].…”

Section: Treatment Implicationsmentioning

confidence: 99%

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

Anderson¹

2023

IJMS

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Type 1 diabetes mellitus (T1DM) arises from the failure of pancreatic β-cells to produce adequate insulin, usually as a consequence of extensive pancreatic β-cell destruction. T1DM is classed as an immune-mediated condition. However, the processes that drive pancreatic β-cell apoptosis remain to be determined, resulting in a failure to prevent ongoing cellular destruction. Alteration in mitochondrial function is clearly the major pathophysiological process underpinning pancreatic β-cell loss in T1DM. As with many medical conditions, there is a growing interest in T1DM as to the role of the gut microbiome, including the interactions of gut bacteria with Candida albicans fungal infection. Gut dysbiosis and gut permeability are intimately associated with raised levels of circulating lipopolysaccharide and suppressed butyrate levels, which can act to dysregulate immune responses and systemic mitochondrial function. This manuscript reviews broad bodies of data on T1DM pathophysiology, highlighting the importance of alterations in the mitochondrial melatonergic pathway of pancreatic β-cells in driving mitochondrial dysfunction. The suppression of mitochondrial melatonin makes pancreatic β-cells susceptible to oxidative stress and dysfunctional mitophagy, partly mediated by the loss of melatonin’s induction of PTEN-induced kinase 1 (PINK1), thereby suppressing mitophagy and increasing autoimmune associated major histocompatibility complex (MHC)-1. The immediate precursor to melatonin, N-acetylserotonin (NAS), is a brain-derived neurotrophic factor (BDNF) mimic, via the activation of the BDNF receptor, TrkB. As both the full-length and truncated TrkB play powerful roles in pancreatic β-cell function and survival, NAS is another important aspect of the melatonergic pathway relevant to pancreatic β-cell destruction in T1DM. The incorporation of the mitochondrial melatonergic pathway in T1DM pathophysiology integrates wide bodies of previously disparate data on pancreatic intercellular processes. The suppression of Akkermansia muciniphila, Lactobacillus johnsonii, butyrate, and the shikimate pathway—including by bacteriophages—contributes to not only pancreatic β-cell apoptosis, but also to the bystander activation of CD8+ T cells, which increases their effector function and prevents their deselection in the thymus. The gut microbiome is therefore a significant determinant of the mitochondrial dysfunction driving pancreatic β-cell loss as well as ‘autoimmune’ effects derived from cytotoxic CD8+ T cells. This has significant future research and treatment implications.

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“…Transforming growth factor-β1-treated NRK-49F cells treated with MT exhibited lower levels of intracellular ROS and malondialdehyde, as well as ameliorated reductions of the glutathione/oxidized glutathione ratio [ 128 ]. Moreover, the addition of MT treatment in diabetic Wistar rats receiving insulin resulted in downregulated expression of GSH, GSH reductase, glucose-6-phosphate dehydrogenase, and GSH-S-transferase in the renal cortex [ 129 ]. MT also improved DN in albino rats by suppressing renal malondialdehyde and stimulating antioxidant systems such as GSH, SOD, and catalase [ 116 ].…”

Section: Antioxidant Pharmacotherapies In Cardiorenal Diseasesmentioning

confidence: 99%

Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin

Theofilis

Vordoni

Kalaitzidis

2022

Life

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Oxidative stress is characterized by excessive production of reactive oxygen species together with exhausted antioxidant defenses. This constitutes a main pathophysiologic process that is implicated in cardiovascular and renal diseases. In particular, enhanced oxidative stress may lead to low-density lipoprotein accumulation and oxidation, endothelial cell activation, adhesion molecule overexpression, macrophage activation, and foam cell formation, promoting the development and progression of atherosclerosis. The deleterious kidney effects of oxidative stress are numerous, including podocytopathy, mesangial enlargement, renal hypertrophy, tubulointerstitial fibrosis, and glomerulosclerosis. The prominent role of oxidative mechanisms in cardiorenal diseases may be counteracted by recently developed pharmacotherapies such as novel antidiabetic agents and finerenone. These agents have demonstrated significant antioxidant activity in preclinical and clinical studies. Moreover, the use of melatonin as a treatment in this field has been experimentally investigated, with large-scale clinical studies being awaited. Finally, clinical implications and future directions in this field are presented.

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Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function

Cited by 14 publications

References 65 publications

Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders

Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin

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