• Cochran Q test
• Melatonin
• diabetes
• glycemic control
• insulin resistance
• protein metabolism.

• Humans
• Melatonin/administration & dosage
• Melatonin/pharmacology
• Melatonin/therapeutic use
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/blood
• Blood Glucose/drug effects
• Blood Glucose/metabolism
• Blood Glucose/analysis
• Dietary Supplements
• Randomized Controlled Trials as Topic

• GI tract
• duodenum
• extra-pineal
• immunohistochemistry
• radioimmunoassay

• Rats
• Animals
• Melatonin/metabolism
• Pineal Gland/metabolism
• Tryptophan/metabolism
• Circadian Rhythm
• Mammals/metabolism

• G protein-coupled receptors
• insulin secretion
• type 2 diabetes mellitus
• β-cell dysfunction

• Humans
• Diabetes Mellitus, Type 2/etiology
• Diabetes Mellitus, Type 2/metabolism
• Melatonin/therapeutic use
• Melatonin/metabolism
• Serotonin
• Insulin
• Insulin-Secreting Cells/metabolism
• Glucose/metabolism

• Blood–brain barrier
• Carotenoids
• Dietary antioxidant supplements
• Flavonoids
• Neurodegenerative diseases
• Oxidative stress
• Polyphenols
• Vitamins

• gut-derived melatonin
• neurobehavioral impairment
• transcriptome sequencing
• zinc oxide nanoparticle exposure

Circadian rhythms are cyclic patterns of physiological, behavioural and molecular events that occur over a 24-h period. They are controlled by the suprachiasmatic nucleus (SCN), the brain’s master pacemaker which governs peripheral clocks and melatonin release. While circadian systems are endogenous, there are external factors that synchronise the SCN to the ambient environment including light/dark cycles, fasting/fed state, temperature and physical activity. Circadian rhythms also provide internal temporal organisation which ensures that any internal changes that take place are centrally coordinated. Melatonin synchronises peripheral clocks to the external time and circadian rhythms are regulated by gene expression to control physiological function. Synchronisation of the circadian system with the external environment is vital for the health and survival of an organism and as circadian rhythms play a pivotal role in regulating GI physiology, disruption may lead to gastrointestinal (GI) dysfunction. Disorders of gut-brain interactions (DGBIs), also known as functional gastrointestinal disorders (FGIDs), are a group of diseases where patients experience reoccurring gastrointestinal symptoms which cannot be explained by obvious structural abnormalities and include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Food timing impacts on the production of melatonin and given the correlation between food intake and symptom onset reported by patients with DGBIs, chronodisruption may be a feature of these conditions. Recent advances in immunology implicate circadian rhythms in the regulation of immune responses, and DGBI patients report fatigue and disordered sleep, suggesting circadian disruption. Further, melatonin treatment has been demonstrated to improve symptom burden in IBS patients, however, the mechanisms underlying this efficacy are unclear. Given the influence of circadian rhythms on gastrointestinal physiology and the immune system, modulation of these rhythms may be a potential therapeutic option for reducing symptom burden in these patients.

• Aging
• Elderly patients
• Melatonin
• MicroRNAs
• Neurological disorders

• Aging
• Animals
• Brain/drug effects
• Brain/metabolism
• Humans
• Melatonin/pharmacology
• Melatonin/therapeutic use
• MicroRNAs
• Neurodegenerative Diseases/drug therapy
• Neurodegenerative Diseases/genetics
• Neuroprotective Agents/pharmacology
• Neuroprotective Agents/therapeutic use

Microbial dysbiosis has long been postulated to be associated with the pathogenesis of inflammatory bowel disease (IBD). Although evidence supporting the anti-colitic effects of melatonin have been accumulating, it is not clear how melatonin affects the microbiota. Herein, we investigated the effects of melatonin on the microbiome in colitis and identified involvement of Toll-like receptor (TLR) 4 signalling in the effects. Melatonin improved dextran sulfate sodium (DSS)-induced colitis and reverted microbial dysbiosis in wild-type (WT) mice but not in TLR4 knockout (KO) mice. Induction of goblet cells was observed with melatonin administration, which was accompanied by suppression of Il1b and Il17a and induction of melatonin receptor and Reg3β, an antimicrobial peptide (AMP) against Gram-negative bacteria. In vitro, melatonin treatment of HT-29 intestinal epithelial cells promotes mucin and wound healing and inhibits growth of Escherichia coli. Herein, we showed that melatonin significantly increases goblet cells, Reg3β, and the ratio of Firmicutes to Bacteriodetes by suppressing Gram-negative bacteria through TLR4 signalling. Our study suggests that sensing of bacteria through TLR4 and regulation of bacteria through altered goblet cells and AMPs is involved in the anti-colitic effects of melatonin. Melatonin may have use in therapeutics for IBD.

• cellular mechanisms
• melatonin
• pain

• Lipopolysaccharide (LPS)
• agomelatine
• immunohistochemistry
• pancreas
• pathology

• Melatonin
• circadian rhythm
• insulin
• melatonin receptor
• oxidative stress
• type 1 and type 2 diabetes
• β- cell.

• gastrointestinal motility
• intestinal barrier integrity
• intestinal microbiota
• melatonin
• spinal cord injury

• Dyslipidemia
• Melatonin
• diabetes mellitus
• oxidative stress
• streptozotocin

• AANAT
• Broilers
• Epinephrine (E)
• Melatonin (MLT)
• Pineal gland

Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence has continued to rise; thus, necessitating more research into its aetiology. Recent researches are beginning to link a dysregulation of the circadian rhythm to impairment of intermediary metabolism; with evidences that circadian rhythm dysfunction might play an important role in the aetiology, course or prognosis of some cases of diabetes mellitus. These evidences thereby suggest possible relationships between the circadian rhythm regulator melatonin, and diabetes mellitus. In this review, we discuss the roles of the circadian rhythm in the regulation of the metabolism of carbohydrates and other macronutrients; with emphasis on the importance of melatonin and the impacts of its deficiency on carbohydrate homeostasis. Also, the possibility of using melatonin and its analogs for the “prophylaxis” or management of diabetes mellitus is also considered.

• Chronobiology
• Dysmetabolism
• Insulin
• Pancreatic beta cell
• Melatonin receptors

Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N¹-acetyl-N¹-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1) Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK) release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2) Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3) In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated.

• AFMK
• acute pancreatitis
• enzyme secretion
• melatonin
• pancreatic cancer

• Animals
• Carcinogenesis/metabolism
• Humans
• Melatonin/analogs & derivatives
• Melatonin/metabolism
• Pancreas/enzymology
• Pancreas/metabolism
• Pancreatic Neoplasms/metabolism
• Pancreatitis/metabolism
• Receptors, Melatonin/metabolism

• Clock gene
• Duodenum
• Liver
• Melatonin
• Pinealectomy
• Suprachiasmatic nucleus

• Animals
• Circadian Rhythm/drug effects
• Circadian Rhythm/physiology
• Darkness
• Female
• Light
• Locomotion/physiology
• Melatonin/metabolism
• Melatonin/physiology
• Photoperiod
• Pineal Gland/metabolism
• Pineal Gland/surgery
• Rats
• Rats, Wistar
• Signal Transduction/physiology
• Suprachiasmatic Nucleus/metabolism

AIM: To detect the levels of serum melatonin and estrogen in women with functional dyspepsia (FD), and to evaluate the possible mechanism of FD.

METHODS: Sixty women diagnosed with FD according to Roman Ⅲ criteria were included into an experimental group, which was further divided into two subgroups: patients with epigastric pain syndrome (EPS) (n = 35) and those with postprandial distress syndrome (PDS) (n = 25). Thirty healthy person were chose as normal controls. Serum melatonin and estrogen levels were measured and analyzed in these subjects.

RESULTS: In the FD group and PDS subgroup, the levels of serum melatonin were significantly higher than that in normal controls (P < 0.05). In the PDS subgroup, the concentration of serum melatonin was significantly higher than that in the EPS subgroup (P < 0.05). There was no significant difference in the concentration of serum melatonin between the EPS subgroup and the normal control group (P > 0.05). PDS patients with severe symptoms displayed a higher melatonin concentration as compared with patients with moderate symptoms (P < 0.05). EPS patients with severe symptoms displayed a lower melatonin concentration as compared with patients with moderate symptoms (P < 0.05). In the FD subgroup (menopausal transition), the concentration of serum estrogen was significantly lower than that in normal controls (P < 0.05). FD patients (menopausal transition) with severe symptoms displayed a lower estrogen concentration as compared with patients with moderate symptoms (P < 0.05). In FD patients (menopausal transition), there was no significant correlation between the levels of serum melatonin and estrogen (r = -0.03, P > 0.05).

CONCLUSION: The alteration of serum melatonin may play a role in the pathogenesis of FD, especially PDS, but has no obvious relation with EPS. Serum melatonin level maybe have certain significance for the diagnosis of various clinical forms of FD. The alteration of serum estrogen may play a role in the development of FD. Supplementing exogenous estrogen may improve symptoms of FD patients with perimenopausal symptoms.

• Functional dyspepsia
• Melatonin
• Estrogen
• Dyspepsia symptom scale

The largest source of melatonin, according to animal studies, is the gastrointestinal (GI) tract but this is not yet thoroughly characterized in humans. This study aims to map the expression of melatonin and its two receptors in human GI tract and pancreas using microarray analysis and immunohistochemistry.

Gene expression data from normal intestine and pancreas and inflamed colon tissue due to ulcerative colitis were analyzed for expression of enzymes relevant for serotonin and melatonin production and their receptors. Sections from paraffin-embedded normal tissue from 42 individuals, representing the different parts of the GI tract (n=39) and pancreas (n=3) were studied with immunohistochemistry using antibodies with specificity for melatonin, MT₁ and MT₂ receptors and serotonin.

Enzymes needed for production of melatonin are expressed in both GI tract and pancreas tissue. Strong melatonin immunoreactivity (IR) was seen in enterochromaffin (EC) cells partially co-localized with serotonin IR. Melatonin IR was also seen in pancreas islets. MT₁ and MT₂ IR were both found in the intestinal epithelium, in the submucosal and myenteric plexus, and in vessels in the GI tract as well as in pancreatic islets. MT₁ and MT₂ IR was strongest in the epithelium of the large intestine. In the other cell types, both MT₂ gene expression and IR were generally elevated compared to MT₁. Strong MT₂, IR was noted in EC cells but not MT₁ IR. Changes in gene expression that may result in reduced levels of melatonin were seen in relation to inflammation.

Widespread gastroenteropancreatic expression of melatonin and its receptors in the GI tract and pancreas is in agreement with the multiple roles ascribed to melatonin, which include regulation of gastrointestinal motility, epithelial permeability as well as enteropancreatic cross-talk with plausible impact on metabolic control.

• Adult
• Case-Control Studies
• Colitis, Ulcerative/genetics
• Colitis, Ulcerative/metabolism
• Colitis, Ulcerative/pathology
• Enterochromaffin Cells/metabolism
• Gastrointestinal Tract/anatomy & histology
• Gastrointestinal Tract/metabolism
• Gene Expression
• Humans
• Immunohistochemistry
• Melatonin/metabolism
• Pancreas/anatomy & histology
• Pancreas/metabolism
• Receptor, Melatonin, MT1/genetics
• Receptor, Melatonin, MT1/metabolism
• Receptor, Melatonin, MT2/genetics
• Receptor, Melatonin, MT2/metabolism
• Serotonin/metabolism
• Tissue Distribution

• 51Cr-EDTA clearance
• duodenal bicarbonate secretion
• ethanol
• intestinal barrier
• intestinal permeability

• alcoholic liver disease
• duodenal barrier
• duodenal bicarbonate secretion
• intestinal barrier dysfunction
• leaky gut syndrome

• Animals
• Gastrointestinal Tract/metabolism
• Isoindoles/pharmacology
• Muscle Contraction
• Muscle, Smooth/metabolism
• Myocytes, Smooth Muscle/metabolism
• Rabbits
• Receptor, Melatonin, MT1/antagonists & inhibitors
• Receptor, Melatonin, MT1/metabolism
• Receptor, Melatonin, MT2/antagonists & inhibitors
• Receptor, Melatonin, MT2/metabolism
• Signal Transduction

• DK15564 NIDDK NIH HHS
• R01 DK034153 NIDDK NIH HHS
• R01 DK028300 NIDDK NIH HHS
• R01 DK015564 NIDDK NIH HHS
• R56 DK034153 NIDDK NIH HHS
• DK34153 NIDDK NIH HHS
• DK28300 NIDDK NIH HHS

Melatonin, a product of the pineal gland, is released from the gut mucosa in response to food ingestion. Specific receptors for melatonin have been detected in many gastrointestinal tissues including the pancreas. Melatonin as well as its precursor, L-tryptophan, attenuates the severity of acute pancreatitis and protects the pancreatic tissue from the damage caused by acute inflammation. The beneficial effect of melatonin on acute pancreatitis, which has been reported in many experimental studies and supported by clinical observations, is related to: (1) enhancement of antioxidant defense of the pancreatic tissue, through direct scavenging of toxic radical oxygen (ROS) and nitrogen (RNS) species, (2) preservation of the activity of antioxidant enzymes; such as superoxide dismutase (SOD), catalase (CAT), or glutathione peroxidase (GPx), (3) the decline of pro-inflammatory cytokine tumor necrosis α (TNFα) production, accompanied by stimulation of an anti-inflammatory IL-10, (4) improvement of pancreatic blood flow and decrease of neutrophil infiltration, (5) reduction of apoptosis and necrosis in the inflamed pancreatic tissue, (6) increased production of chaperon protein (HSP60), and (7) promotion of regenerative process in the pancreas. Conclusion. Endogenous melatonin produced from L-tryptophan could be one of the native mechanisms protecting the pancreas from acute damage and accelerating regeneration of this gland. The beneficial effects of melatonin shown in experimental studies suggest that melatonin ought to be employed in the clinical trials as a supportive therapy in acute pancreatitis and could be used in people at high risk for acute pancreatitis to prevent the development of pancreatic inflammation.

• Clinical trial
• Colon
• Ileum
• Inflammatory bowel disease
• Melatonin
• Motility
• Receptor

• Animals
• Clinical Trials as Topic
• Colon/metabolism
• Gastrointestinal Diseases/physiopathology
• Gastrointestinal Motility/physiology
• Gastrointestinal Tract/anatomy & histology
• Gastrointestinal Tract/physiology
• Humans
• Ileum/metabolism
• Melatonin/metabolism
• Receptors, Melatonin/metabolism

• Animals
• Apoptosis/drug effects
• Calcium/metabolism
• Caspase 3/metabolism
• Cell Line, Tumor
• Cell Survival/drug effects
• Melatonin/pharmacology
• Membrane Potential, Mitochondrial/drug effects
• Mitochondria/drug effects
• Mitochondria/metabolism
• Rats

• Animals
• Antioxidants/pharmacology
• Calcium/metabolism
• Cell Line, Tumor
• Cytosol/drug effects
• Cytosol/metabolism
• Enzyme Inhibitors/pharmacology
• Melatonin/pharmacology
• Rats
• Sincalide/metabolism
• Thapsigargin/pharmacology