Short Communication: Taurine Long-Term Treatment Prevents the Development of Cardiac Hypertrophy, and Premature Death in Hereditary Cardiomyopathy of the Hamster Is Sex-Independent.

Recently, we reported that during the hypertrophic phase (230 days old) of hereditary cardiomyopathy of the hamster (HCMH), short-term treatment (20 days) with 250 mg/kg/day of taurine prevents the development of hypertrophy in males but not in females. However, the mortality rate in non-treated animals was higher in females than in males. To verify whether the sex-dependency effect of taurine is due to the difference in the disease's progression, we treated the 230-day-old animals for a longer time period of 122 days. Our results showed that long-term treatment with low and high concentrations of taurine significantly prevents cardiac hypertrophy and early death in HCMH males (p < 0.0001 and p < 0.05, respectively) and females (p < 0.01 and p < 0.0001, respectively). Our results demonstrate that the reported sex dependency of short-term treatments with taurine is due to a higher degree of heart remodeling in females when compared to males and not to sex dependency. In addition, sex-dependency studies should consider the differences between the male and female progression of the disease. Thus, long-term taurine therapies are recommended to prevent remodeling and early death in hereditary cardiomyopathy.

Taurine ameliorates sensorimotor function by inhibiting apoptosis and activating A2 astrocytes in mice after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a form of severe acute stroke with very high mortality and disability rates. Early brain injury (EBI) and delayed cerebral ischemia (DCI) contribute to the poor prognosis of patients with SAH. Currently, some researchers have started to focus on changes in amino acid metabolism that occur in brain tissues after SAH. Taurine is a sulfur-containing amino acid that is semi-essential in animals, and it plays important roles in various processes, such as neurodevelopment, osmotic pressure regulation, and membrane stabilization. In acute stroke, such as cerebral hemorrhage, taurine plays a neuroprotective role. However, the role of taurine after subarachnoid hemorrhage has rarely been reported. In the present study, we established a mouse model of SAH. We found that taurine administration effectively improved the sensorimotor function of these mice. In addition, taurine treatment alleviated sensorimotor neuron damage and reduced the proportion of apoptotic cells. Furthermore, taurine treatment enhanced the polarization of astrocytes toward the neuroprotective phenotype while inhibiting their polarization toward the neurotoxic phenotype. This study is the first to reveal the relationship between taurine and astrocyte polarization and may provide a new strategy for SAH research and clinical treatment.

Taurine amino acid supplementation impacts performance, blood hematology, oxidative stress, and jejunum morphology in broiler chickens.

Excess levels of free radicals cause oxidative damage to cells. Taurine is a rare amino acid with antioxidant effects whose dietary deficiency increases oxidative damage to the cell membrane. To investigate the effects of dietary taurine supplementation on performance, blood hematology, oxidative stress, and jejunum morphology in broilers, 300 broilers (Ras 308, 1D of age) were randomly allocated into 4 groups with 5 replicates of 15 birds. The experimental treatments included basic diet (control treatment) and basic diet with 1, 3, and 6 g/kg taurine amino acid. During 1 to 45 days, the inclusion of taurine supplementation in diets improved the body weight gain (BWG), feed consumption (FC), and feed conversion ratio (FCR) of broilers (P < 0.05). In CBC tests, the experimental treatments were significantly different concerning the red blood cell (RBC) count, the average hemoglobin in the cell, the RBC width in the curve, and the hematocrit (P < 0.05). Despite the significance of oxidative stress among the treatments, the control and fourth treatments showed the highest and the lowest oxidative stress, respectively (P < 0.05). Also, in jejunum morphology, the fourth treatment showed the best performance in terms of villus length and width and the villus length to crypt depth (V/C) ratio (P < 0.05). Overall, 6 g/kg taurine addition to the diet reduced oxidative stress and positive features in the jejunum morphology while improving the functional traits of broilers.

Taurine activates the AKT-mTOR axis to restore muscle mass and contractile strength in human 3D in vitro models of steroid myopathy.

Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.

Improvement of diabetes-induced spinal cord axon injury with taurine via nerve growth factor-dependent Akt/mTOR pathway.

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF-pAKT-mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway.

Deletion of hepatocyte cysteine dioxygenase type 1, a bile acid repressed gene, enhances glutathione synthesis and ameliorates acetaminophen hepatotoxicity.

Liver is a major organ that metabolizes sulfur amino acids cysteine, which is the substrate for the synthesis of many essential cellular molecules including GSH, taurine, and coenzyme A. Bile acid-activated farnesoid x receptor (FXR) inhibits cysteine dioxygenase type 1 (CDO1), which mediates hepatic cysteine catabolism and taurine synthesis. To define the impact of bile acid inhibition of CDO1 on hepatic sulfur amino acid metabolism and antioxidant capacity, we developed hepatocyte-specific CDO1 knockout mice (Hep-CDO1 KO) and hepatocyte specific CDO1 transgenic mice (Hep-CDO1 Tg). Liver metabolomics revealed that genetic deletion of hepatic CDO1 reduced de novo taurine synthesis but had no impact on hepatic taurine abundance or bile acid conjugation. Consistent with reduced cysteine catabolism, Hep-CDO1 KO mice showed increased hepatic cysteine abundance but unaltered methionine cycle intermediates and coenzyme A synthesis. Upon acetaminophen overdose, Hep-CDO1 KO mice showed increased GSH synthesis capacity and alleviated liver injury. In contrast, hepatic CDO1 overexpression in Hep-CDO1 Tg mice stimulated hepatic cysteine to taurine conversion, resulting in reduced hepatic cysteine abundance. However, Hep-CDO1 Tg mice and WT showed similar susceptibility to acetaminophen-induced liver injury. Hep-CDO1 Tg mice showed similar hepatic taurine and coenzyme A compared to WT mice. In summary, these findings suggest that bile acid and FXR signaling inhibition of CDO1-mediated hepatic cysteine catabolism preferentially modulates hepatic GSH synthesis capacity and antioxidant defense, but has minimal effect on hepatic taurine and coenzyme A abundance. Repression of hepatic CDO1 may contribute to the hepatoprotective effects of FXR activation under certain pathologic conditions.

Taurine reduces microglia activation in the brain of aged senescence-accelerated mice by increasing the level of TREM2.

Alzheimer's disease (AD), a chronic neurodegenerative disorder, is the leading cause of dementia. Over-activated microglia is related to amyloid-beta (Aß) and phosphorylated tau (phospho-tau) accumulation in the AD brain. Taurine is an amino acid with multiple physiological functions including anti-inflammatory effects, and has been reported to be neuroprotective in AD. However, the role of taurine in microglia-mediated AD remains unclear. Here, we examined the effects of taurine on the brains of senescence-accelerated mouse prone 8 (SAMP8) mice by comparing those administered 1% taurine water with those administered distilled water (DW). We observed increased levels of taurine and taurine transporter (TAUT) in the brains of the taurine-treated mice compared with those of control mice. Immunohistochemical and Western blot analyses revealed that taurine significantly reduced the number of activated microglia, levels of phospho-tau and Aß deposit in the hippocampus and cortex. Triggering receptors expressed on myeloid cells-2 (TREM2) are known to protect against AD pathogenesis. Taurine upregulated TREM2 expression in the hippocampus and cortex. In conclusion, the present study suggests that taurine treatment may upregulate TREM2 to protect against microglia over-activation by decreasing the accumulation of phospho-tau and Aß; providing an insight into a novel preventive strategy in AD.

Effect of Natural Osmolytes on Recombinant Tau Monomer: Propensity of Oligomerization and Aggregation.

The pathological misfolding and aggregation of the microtubule associated protein tau (MAPT), a full length Tau2N4R with 441aa, is considered the principal disease relevant constituent in tauopathies including Alzheimer's disease (AD) with an imbalanced ratio in 3R/4R isoforms. The exact cellular fluid composition, properties, and changes that coincide with tau misfolding, seed formation, and propagation events remain obscure. The proteostasis network, along with the associated osmolytes, is responsible for maintaining the presence of tau in its native structure or dealing with misfolding. In this study, for the first time, the roles of natural brain osmolytes are being investigated for their potential effects on regulating the conformational stability of the tau monomer (tauM) and its propensity to aggregate or disaggregate. Herein, the effects of physiological osmolytes myo-inositol, taurine, trimethyl amine oxide (TMAO), betaine, sorbitol, glycerophosphocholine (GPC), and citrulline on tau's aggregation state were investigated. The overall results indicate the ability of sorbitol and GPC to maintain the monomeric form and prevent aggregation of tau, whereas myo-inositol, taurine, TMAO, betaine, and citrulline promote tau aggregation to different degrees, as revealed by protein morphology in atomic force microscopy images. Biochemical and biophysical methods also revealed that tau proteins adopt different conformations under the influence of these osmolytes. TauM in the presence of all osmolytes expressed no toxicity when tested by a lactate dehydrogenase assay. Investigating the conformational stability of tau in the presence of osmolytes may provide a better understanding of the complex nature of tau aggregation in AD and the protective and/or chaotropic nature of osmolytes.

Taurine Prevents Angiotensin II-Induced Human Endocardial Endothelium Morphological Remodeling and the Increase in Cytosolic and Nuclear Calcium and ROS.

Endocardial endothelium (EE) is a layer of cells covering the cardiac cavities and modulates cardiomyocyte function. This cell type releases several cardioactive factors, including Angiotensin II (Ang II). This octopeptide is known to induce cardiac hypertrophy. However, whether this circulating factor also induces EE hypertrophy is not known. Taurine is known to prevent cardiac hypertrophy. Whether this endogenous antioxidant prevents the effect of Ang II on human EE (hEE) will be verified. Using quantitative fluorescent probe imaging for calcium and reactive oxygen species (ROS), our results show that Ang II induces (10-7 M, 48 h treatment) an increase in hEE cell (hEEC) volume and its nucleus. Pretreatment with 20 mM of taurine prevents morphological remodeling and increases intracellular calcium and ROS. These results suggest that the reported Ang II induces cardiac hypertrophy is associated with hEEC hypertrophy. This later effect is prevented by taurine by reducing intracellular calcium and ROS overloads. Thus, taurine could be an excellent tool for preventing Ang II-induced remodeling of hEECs.

Effects of taurine, cysteine and melatonin as antioxidant supplements to the freezing medium of Prochilodus brevis sperm.

Cryopreservation consist of a set of methods to preserve cells and tissues by drastically reducing the temperature. Among some undesired effects, cryopreservation might generate reactive oxygen species that lead to an increase of oxidative stress, causing damage to cells. This study aimed to test taurine, cysteine, and melatonin on the freezing of Prochilodus brevis sperm and assess its effects on post-thawed sperm quality. Sperm was collected and seven pools were formed (n = 7). They were diluted (1:9) in standard medium (5% glucose, 10% dimethyl sulfoxide and 5% egg yolk) supplemented or not (control) with taurine (0.3, 1.0, 3.16 or 10.0 mM), cysteine (0.3, 1.0, 3.16 or 10.0 mM) or melatonin (0.6, 1.12, 2.0 or 3.56 mM). Post-thawed sperm was evaluated for kinetic (total motility, velocities, and percentage of rapid cells), morphology and membrane and DNA integrity. Differences were found when melatonin was used as an antioxidant. For the variables rapid sperm and sperm velocities, 3.56 mM melatonin presented higher results than the control (melatonin 0 mM). Melatonin 2 mM was similar to 3.56 mM on rapid sperm, average path velocity (VAP) and curvilinear velocity (VCL). No difference was found between concentration 0 mM (control) and taurine treatments. As for cysteine, 0.3 mM presented the best results for rapid sperm than 10 mM, and higher VCL and VAP than 1 mM. Melatonin 3.56 mM presented higher results on kinetic parameters (rapid motility, VCL, VSL and VAP) than other tested antioxidants. Therefore, melatonin 3.56 mM is recommended to be added to the sperm freezing medium of P. brevis.

Investigation of the effects of in ovo taurine injection on hatching characteristics and stress reduction potential.

BACKGROUND: In ovo application is the process of administering some nutrients or components into the egg. The main purpose of this application is to ensure that some nutrients are provided to chicks with a short incubation period. Few studies were conducted with taurine in fertile eggs; especially, no observation of hatchability and chick quality has been found. In addition, taurine has an anti-stress impact that fights oxidative factors. OBJECTIVE: To assess the hatchability and chick quality after in ovo taurine administration. To determine the stress that may occur as a result of in ovo application and whether taurine has a stress-reducing effect. METHODS: A total of 1200 fertile eggs from a 34-week-old broiler breeder (Ross 308) flock were categorized into 4 groups with 75 eggs per replicate: control (uninjected), taurine group (0.30 mL dissolved taurine in distilled water), sham control (sterile distilled water) and perforation (eggs perforated and then waxed). On day 14 of incubation, an in ovo injection was administered to the albumen. Data on hatching parameters and hepatic HSP70 levels were obtained using relevant formulas and western blotting, respectively. RESULTS: Control chicks exhibited higher hatchability than other groups, with the taurine group showing the lowest hatchability. The HSP70 levels were the highest in the perforation group compared to the control group. An increase of 21.37% in the taurine group and 83.45% in the sham control group was observed compared to the control group. CONCLUSIONS: The findings suggest that in ovo application may induce increased stress, whereas taurine may have positive effects in mitigating the stress caused by in ovo application.

Involvement of GAT2/Slc6a13 in hypotaurine uptake at fetal-facing plasma membrane of syncytiotrophoblasts at mid-to-late gestation in rats and mice.

INTRODUCTION: Hypotaurine, a precursor to taurine, is known for its antioxidant properties and is prominently present in fetal plasma and the placenta. Our previous research revealed that ezrin-knockout mice experience fetal growth retardation, coinciding with reduced hypotaurine levels in fetal plasma. This study aims to elucidate the expression and role of hypotaurine transporters within the placenta. METHODS: We employed quantitative RT-PCR to measure mRNA expression of GAT transporter family members in the placenta during mid-to-late gestation. LC/MS/MS was used to analyze the distribution of hypotaurine in different placental subregions. Immunohistochemistry was utilized to examine the localization of GAT2 in mice. Placental hypotaurine uptake from fetal circulation was studied via umbilical perfusion in rats. RESULTS: Among hypotaurine transporters, GAT2 exhibited increased mRNA and protein expression in murine placenta during mid-to-late gestation. Notably, GAT2/Slc6a13 mRNA and hypotaurine were most concentrated in the labyrinth of murine placenta. In contrast, enzymes responsible for hypotaurine synthesis, such as cysteine dioxygenase, cysteine sulfinic acid decarboxylase, and 2-aminoethanethiol dioxygenase, showed minimal expression in the labyrinth. These findings suggest that GAT2 is a key determinant of hypotaurine levels in the placental labyrinth. Immunohistochemical examination unveiled that GAT2 was predominantly localized on the fetal-facing plasma membrane within syncytiotrophoblasts, which co-localized with ezrin. In rat umbilical perfusion experiments, the GAT2/3 and TauT inhibitor, SNAP-5114, significantly reduced hypotaurine extraction from fetal circulation to the placenta. DISCUSSION: The results suggest that GAT2 plays a pivotal role in the concentrative uptake of hypotaurine from fetal plasma within syncytiotrophoblasts of the placenta.

Acute taurine reduced alcohol intake and preference in alcohol-experienced, but not in alcohol-näive rats by central mechanisms.

Taurine is a non-essential ß sulfonated amino acid involved in a plethora of biological functions in the mammalian central nervous system. Taurine is easily accessible in energy drinks for human consumption. Previous preclinical and clinical reports suggest that acute systemic administration of taurine could inhibit some of the behavioral and metabolic effects of alcohol use disorder. Overall, both in rodent and human studies, acute taurine administration reduced voluntary alcohol intake. This study aimed to assess the pharmacological effects of taurine (intracerebroventricular; i.c.v.) on ethanol intake/preference of rats either control (i.e., alcohol naïve) or forced ethanol intake (since juvenile age with a chronic intermittent access model). In addition, to explore anxiety-like behavior (through defensive burying behavior test) as pharmacological control of taurine. We found that acute (i.c.v.) taurine reduced alcohol consumption, i.e., taurine significantly decreased both alcohol intake and preference in adult male Wistar rats. Moreover, taurine elicits an anxiolytic-like effect in all administered groups independently of previous alcohol exposure.

Molecular determinants and intracellular targets of taurine signalling in pancreatic islet ß-cells.

AIM: Despite its abundance in pancreatic islets of Langerhans and proven antihyperglycemic effects, the impact of the essential amino acid, taurine, on islet ß-cell biology has not yet received due consideration, which prompted the current studies exploring the molecular selectivity of taurine import into ß-cells and its acute and chronic intracellular interactions. METHODS: The molecular aspects of taurine transport were probed by exposing the clonal pancreatic BRIN BD11 ß-cells and primary mouse and human islets to a range of the homologs of the amino acid (assayed at 2-20 mM), using the hormone release and imaging of intracellular signals as surrogate read-outs. Known secretagogues were employed to profile the interaction of taurine with acute and chronic intracellular signals. RESULTS: Taurine transporter TauT was expressed in the islet ß-cells, with the transport of taurine and homologs having a weak sulfonate specificity but significant sensitivity to the molecular weight of the transporter. Taurine, hypotaurine, homotaurine, and ß-alanine enhanced insulin secretion in a glucose-dependent manner, an action potentiated by cytosolic Ca2+ and cAMP. Acute and chronic ß-cell insulinotropic effects of taurine were highly sensitive to co-agonism with GLP-1, forskolin, tolbutamide, and membrane depolarization, with an unanticipated indifference to the activation of PKC and CCK8 receptors. Pre-culturing with GLP-1 or KATP channel inhibitors sensitized or, respectively, desensitized ß-cells to the acute taurine stimulus. CONCLUSION: Together, these data demonstrate the pathways whereby taurine exhibits a range of beneficial effects on insulin secretion and ß-cell function, consistent with the antidiabetic potential of its dietary low-dose supplementation.

Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor-Associated Macrophages in Prostate Cancer.

Tumor-associated macrophages (TAMs) play an essential role in tumor therapeutic resistance. Although the lethal effect of ferroptosis on tumor cells is well reported, how TAMs inhibit the effect of ferroptosis in tumors has not been clearly defined. In this study, it is demonstrated that TAM-secreted taurine suppresses ferroptosis in prostate cancer (PCa) by activating the Liver X receptor alpha/Stearoyl-Coenzyme A desaturase 1 (LXRα/SCD1) pathway. Blocking taurine intake via inhibition of taurine transporter TauT restores the sensitivity to ferroptosis in tumors. Furthermore, LXRα activates the transcription of both miR-181a-5p and its binding protein FUS to increase the recruitment of miR-181a-5p in tumor-derived extracellular vesicles (EVs). It is observed that macrophages appear to be recipient cells of the miR-181a-5p-enriched EVs. Intake of miR-181a-5p in macrophages promotes their M2 polarization and enhances the taurine export by inhibiting expression of its target gene lats1, which in turn inactivates the hippo pathway and results in a Yes-associated protein (YAP) nuclear translocation for transcriptional activation of both M2 polarization-related genes such as ARG1 and CD163 and the taurine transport gene TauT. Taken together, the findings indicate a reciprocal interaction between PCa cells and TAMs as a positive feedback-loop to repress ferroptosis in PCa, mediated by TAM-secreted taurine and tumor EV-delivered miR-181a-5p.

Pre/postnatal taurine supplementation improves neurodevelopment and brain function in mice offspring: A persistent developmental study from puberty to maturity.

Taurine (TAU) is a sulfur-containing amino acid abundantly found in the human body. Endogenously, TAU is synthesized from cysteine in the liver. However, newborns rely entirely on TAU's dietary supply (milk). There is no investigation on the effect of long-term TAU administration on next-generation neurological development. The current study evaluated the effect of long-term TAU supplementation during the maternal gestational and litter weaning time on several neurological parameters in mice offspring. Moreover, the effects of TAU on mitochondrial function and oxidative stress biomarkers as plausible mechanisms of its action in the whole brain and hippocampus have been evaluated. TAU (0.5 % and 1 % w/v) was dissolved in the drinking water of pregnant mice (Day one of pregnancy), and amino acid supplementation was continued during the weaning time (post-natal day; PND = 21) until litters maturity (PND = 65). It was found that TAU significantly improved cognitive function, memory performance, reflexive motor activity, and emotional behaviors in F1-mice generation. TAU measurement in the brain and hippocampus revealed higher levels of this amino acid. TAU and ATP levels were also significantly higher in the mitochondria isolated from the whole brain and hippocampus. Based on these data, TAU could be suggested as a supplement during pregnancy or in pediatric formula. The effects of TAU on cellular mitochondrial function and energy metabolism might play a fundamental role in the positive effects of this amino acid observed in this investigation.

Exogenous taurine administration abates reproductive dysfunction in male rats exposed to silver nanoparticles.

The broad contemporary applications of silver nanoparticles (AgNPs) have been associated with various toxicities including reproductive toxicity. Taurine is well acknowledged for its potent pharmacological role in numerous disease models and chemically-mediated toxicity. We investigated the effect of taurine on AgNPs-induced reproductive toxicity in male rats. The animals were intraperitoneally injected with AgNPs (200 µg/kg) alone or co-administered with taurine at 50 and 100 mg/kg for 21 successive days. Exogenous taurine administration significantly abated AgNPs-induced oxidative injury by decreasing the levels of oxidative stress indices while boosting antioxidant enzymes activities and glutathione level in the hypothalamus, testes and epididymis of exposed animals. Taurine administration alleviated AgNPs-induced inflammatory response and caspase-3 activity, an apoptotic biomarker. Moreover, taurine significantly improved spermiogram, reproductive hormones and the marker enzymes of testicular function in AgNPs-treated animals. The ameliorative effect of taurine on pathological lesions induced by AgNPs in the exposed animals was substantiated by histopathological data. This study provides the first mechanistic evidence that taurine supplementation affords therapeutic effect against reproductive dysfunction associated with AgNPs exposure in male rats.

Identification of a novel enzyme and the regulation of key enzymes in mammalian taurine synthesis.

Taurine has many pharmacological roles on various tissues. The maintenance of abundant taurine content in the mammalian body through endogenous synthesis, in addition to exogenous intake, is the essential factor for morphological and functional maintenances in most tissues. The synthesis of taurine from sulfur-containing amino acids is influenced by various factors. Previous literature findings indicate the influence of the intake of proteins and sulfur-containing amino acids on the activity of the rate-limiting enzymes cysteine dioxygenase and cysteine sulfinate decarboxylase. In addition, the regulation of the activity and expression of taurine-synthesis enzymes by hormones, bile acids, and inflammatory cytokines through nuclear receptors have been reported in liver and reproductive tissues. Furthermore, flavin-containing monooxygenase subtype 1 was recently identified as the taurine-synthesis enzyme that converts hypotaurine to taurine. This review introduces the novel taurine synthesis enzyme and the nuclear receptor-associated regulation of key enzymes in taurine synthesis.

Taurine promotes insulin synthesis by enhancing Isl-1 expression through miR-7a/RAF1/ERK1/2 pathway.

It has been well established that the circulating taurine affects the insulin synthesis in pancreatic islet ß-cells, whereas miR-7a and LIM-homeodomain transcription factor Isl-1 are important intracellular factors regulating insulin transcription and synthesis. However, it still remains unknown whether taurine regulates insulin synthesis by affecting miR-7a and/or Isl-1 expressions in mouse pancreatic islet ß-cells. The present study was thus proposed to identify the effects of taurine on the expressions of miR-7a and/or Isl-1 and their relations to insulin synthesis in mouse pancreatic islet ß-cells by using miR-7a2 knockout (KO) and taurine transporter (TauT) KO mouse models and the related in vitro experiments. The results demonstrated that taurine supplement significantly decreased the pancreas miR-7a expression, but sharply upregulated the pancreas Isl-1 and insulin expressions, and serum insulin levels. However, the enhanced effects of taurine on Isl-1 expression and insulin synthesis were mitigated in the TauT KO and miR-7a2 KO mice. In addition, our results confirmed that taurine markedly increased pancreas RAF1 and ERK1/2 expressions. Collectively, the present study firstly demonstrates that taurine regulates insulin synthesis through TauT/miR-7a/RAF1/ERK1/2/Isl-1 signaling pathway, which are crucial for our understanding the mechanisms of taurine affecting insulin synthesis, and also potential for establishing the therapeutic strategies for diabetes and the diseases related to metabolism.