Adipose tissue macrophages (ATM) of obese patients are releasing increased levels of prolactin during an inflammatory challenge: a role for prolactin in diabesity?

BACKGROUND: Obesity, characterized by low grade inflammation, induces adipose tissue macrophage (ATM) infiltration in white adipose tissue (AT) in both humans and rodents, thus contributing to insulin resistance. Previous studies have shown altered prolactin secretion in obesity, however, studies linking ATM infiltration and prolactin (PRL) secretion to the pathogenesis of the metabolic syndrome, obesity and diabetes are lacking. METHODS/RESULTS: In vivo, qPCR and Western blot analysis demonstrated that prolactin expression was increased in AT of obese rats and also in human AT from obese, obese pre-diabetic and obese diabetic compared to lean counterparts. Immunohistochemistry of obese rat and human AT sections demonstrated a specific expression of prolactin in macrophages. In vitro, we demonstrated that hyperglycemia and inflammation stimulated macrophages (human THP-1 cell line and sorted rat ATM) to express PRL, when challenged with different glucose concentrations with or without IL1ß. In in vivo and in vitro experiments, we assessed the expression of Pit-1 (PRL-specific transcription factor) and found that its expression was parallel to PRL expression. CONCLUSIONS: In this study, we show that rodent and human macrophages synthesize prolactin in response to inflammation and high glucose concentrations. GENERAL SIGNIFICANCE: Our data shed new light on the potential role of macrophages in the physiopathology of diabesity via the PRL expression and on its expression mechanism and regulation.

The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines.

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic beta cells are killed by infiltrating immune cells and by cytokines released by these cells. Signaling events occurring in the pancreatic beta cells are decisive for their survival or death in diabetes. We have used RNA sequencing (RNA-seq) to identify transcripts, including splice variants, expressed in human islets of Langerhans under control conditions or following exposure to the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ). Based on this unique dataset, we examined whether putative candidate genes for T1D, previously identified by GWAS, are expressed in human islets. A total of 29,776 transcripts were identified as expressed in human islets. Expression of around 20% of these transcripts was modified by pro-inflammatory cytokines, including apoptosis- and inflammation-related genes. Chemokines were among the transcripts most modified by cytokines, a finding confirmed at the protein level by ELISA. Interestingly, 35% of the genes expressed in human islets undergo alternative splicing as annotated in RefSeq, and cytokines caused substantial changes in spliced transcripts. Nova1, previously considered a brain-specific regulator of mRNA splicing, is expressed in islets and its knockdown modified splicing. 25/41 of the candidate genes for T1D are expressed in islets, and cytokines modified expression of several of these transcripts. The present study doubles the number of known genes expressed in human islets and shows that cytokines modify alternative splicing in human islet cells. Importantly, it indicates that more than half of the known T1D candidate genes are expressed in human islets. This, and the production of a large number of chemokines and cytokines by cytokine-exposed islets, reinforces the concept of a dialog between pancreatic islets and the immune system in T1D. This dialog is modulated by candidate genes for the disease at both the immune system and beta cell level.

Non-invasive quantification of the beta cell mass by SPECT with ¹¹¹In-labelled exendin.

AIMS/HYPOTHESIS: A reliable method for in vivo quantification of pancreatic beta cell mass (BCM) could lead to further insight into the pathophysiology of diabetes. The glucagon-like peptide 1 receptor, abundantly expressed on beta cells, may be a suitable target for imaging. We investigated the potential of radiotracer imaging with the GLP-1 analogue exendin labelled with indium-111 for determination of BCM in vivo in a rodent model of beta cell loss and in patients with type 1 diabetes and healthy individuals. METHODS: The targeting of (111)In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq (111)In-labelled exendin and single photon emission computed tomography (SPECT) acquisition was performed 1 h post injection, followed by dissection, biodistribution and ex vivo autoradiography studies of pancreatic sections. BCM was determined by morphometric analysis after staining with an anti-insulin antibody. For clinical evaluation SPECT was acquired 4, 24 and 48 h after injection of 150 MBq (111)In-labelled exendin in five patients with type 1 diabetes and five healthy individuals. The tracer uptake was determined by quantitative analysis of the SPECT images. RESULTS: In rats, (111)In-labelled exendin specifically targets the beta cells and pancreatic uptake is highly correlated with BCM. In humans, the pancreas was visible in SPECT images and the pancreatic uptake showed high interindividual variation with a substantially lower uptake in patients with type 1 diabetes. CONCLUSIONS/INTERPRETATION: These studies indicate that (111)In-labelled exendin may be suitable for non-invasive quantification of BCM. TRIAL REGISTRATION: ClinicalTrials.gov NCT01825148, EudraCT: 2012-000619-10.

Diabetes during pregnancy influences Hofbauer cells, a subtype of placental macrophages, to acquire a pro-inflammatory phenotype.

Growing evidence indicates that maternal pathophysiological conditions, such as diabetes, influence fetal growth and could program metabolic disease in adulthood. Placental cells, particularly Hofbauer cells (HBCs), which are placental macrophages characterized by an anti-inflammatory profile (M2), can sense the modified maternal environment. The goal of this study was to investigate the direct effect of hyperglycemia on HBCs. We studied, at mRNA and protein levels, some markers of M2 and M1 (pro-inflammatory) macrophages in placentae from control and diabetic patients to assess the balance between pro- and anti-inflammatory macrophages: an imbalance of M2 to M1 macrophages has been observed in humans. We used pregnant rats, receiving a single injection of streptozotocin (STZ), as a model of maternal diabetes. We noticed a M2-to-M1 macrophage unbalance as we observed in human. An in vitro model of isolated rat HBCs was used to identify the direct effects of high glucose. We found that high glucose stimulation activated genes belonging to TLR (Toll-Like Receptor)-dependent inflammatory pathways. Moreover, the HBCs stimulated by high glucose switched their M2 profile towards M1, with increased expression of pro-inflammatory cytokines and markers. We also noticed that the oxidative-stress pathway was activated in response to high glucose driven by Hif-1α. In this study, we demonstrated that diabetes/hyperglycemia affect the anti-inflammatory profile of HBCs, by stimulating these cells to acquire an inflammatory profile leading to adverse consequences for the fetal-placental-maternal axis.

STAT1 is a master regulator of pancreatic {beta}-cell apoptosis and islet inflammation.

Cytokines produced by islet-infiltrating immune cells induce ß-cell apoptosis in type 1 diabetes. The IFN-γ-regulated transcription factors STAT1/IRF-1 have apparently divergent effects on ß-cells. Thus, STAT1 promotes apoptosis and inflammation, whereas IRF-1 down-regulates inflammatory mediators. To understand the molecular basis for these differential outcomes within a single signal transduction pathway, we presently characterized the gene networks regulated by STAT1 and IRF-1 in ß-cells. This was done by using siRNA approaches coupled to microarray analysis of insulin-producing cells exposed or not to IL-1ß and IFN-γ. Relevant microarray findings were further studied in INS-1E cells and primary rat ß-cells. STAT1, but not IRF-1, mediates the cytokine-induced loss of the differentiated ß-cell phenotype, as indicated by decreased insulin, Pdx1, MafA, and Glut2. Furthermore, STAT1 regulates cytokine-induced apoptosis via up-regulation of the proapoptotic protein DP5. STAT1 and IRF-1 have opposite effects on cytokine-induced chemokine production, with IRF-1 exerting negative feedback inhibition on STAT1 and downstream chemokine expression. The present study elucidates the transcriptional networks through which the IFN-γ/STAT1/IRF-1 axis controls ß-cell function/differentiation, demise, and islet inflammation.

Maternal low-protein diet alters pancreatic islet mitochondrial function in a sex-specific manner in the adult rat.

Mitochondrial dysfunction may be a long-term consequence of a poor nutritional environment during early life. Our aim was to investigate whether a maternal low-protein (LP) diet may program mitochondrial dysfunction in islets of adult progeny before glucose intolerance ensues. To address this, pregnant Wistar rats were fed isocaloric diets containing either 20% protein (control) or 8% protein (LP diet) throughout gestation. From birth, offspring received the control diet. The mitochondrial function was analyzed in islets of 3-mo-old offspring. Related to their basal insulin release, cultured islets from both male and female LP offspring presented a lower response to glucose challenge and a blunted ATP production compared with control offspring. The expression of malate dehydrogenase as well as the subunit 6 of the ATP synthase encoded by mitochondrial genome (mtDNA) was lower in these islets, reducing the capacity of ATP production through the Krebs cycle and oxidative phosphorylation. However, mtDNA content was unchanged in LP islets compared with control. Several consequences of protein restriction during fetal life were more marked in male offspring. Only LP males showed an increased reactive oxygen species production associated with a higher expression of mitochondrial subunits of the electron transport chain NADH-ubiquinone oxireductase subunit 4L, an overexpression of peroxisome proliferator-activated receptor-gamma and uncoupling protein-2, and a strongly reduced beta-cell mass. In conclusion, mitochondrial function is clearly altered in islets from LP adult offspring in a sex-specific manner. That may provide a cellular explanation for the earlier development of glucose intolerance in male than in female offspring of dams fed an LP diet.

Neurotrophin-directed differentiation of human adult marrow stromal cells to dopaminergic-like neurons.

Marrow-isolated adult multilineage inducible (MIAMI) cells were differentiated in vitro to neuronal cells in a neurotrophin-dependent fashion. After induction, the cells revealed electrophysiological features similar to those observed in mature neurons. Primary early passage human MIAMI cells without any type of co-cultures with other cell types were used. The developmental program involved a multi-step process requiring the concerted action of brain-derived neurotrophic factor, nerve growth factor and depended on neurotrophin-3, after basic fibroblast growth factor withdrawal. MIAMI-derived neuron-like cells sequentially expressed the neuronal markers, developed a complex neurite outgrowth and arborization, and acquired electrophysiological characteristics similar to those observed in mature neurons. The young and old MIAMI-derived neuronal cells developed both inward and outward currents upon depolarization, similar to those observed in normal neurons. These results represent the earliest evidence that neurotrophin-3 can direct the differentiation of non-neural stem cells from human adult bone marrow stroma to neuron-like cells in vitro. Supplementing the aforementioned multi-step process with sonic hedgehog, fibroblast growth factor 8, and retinoic acid increased the expression of molecules involved in dopaminergic differentiation and of tyrosine hydroxylase, the rate limiting enzyme of dopamine synthesis. MIAMI cells from young and old individuals represent autologous human cell populations for the treatment of disorders of the skeletal and nervous systems and for applications in cell therapy and reparative medicine approaches.

Expression of progenitor cell markers during expansion of sorted human pancreatic beta cells.

Functional pancreatic beta cell mass is dynamic and although fully differentiated, beta cells are capable of reentering the cell cycle upon appropriate stimuli. Stimulating regeneration-competent cells in situ is clearly the most desirable way to restore damaged tissue. Regeneration by dedifferentiation and transdifferentiation is a potential source of cells exhibiting a more developmentally immature phenotype and a wide differentiation potential. In this context and to gain a better understanding of the transformation induced in human beta cells during forced in vitro expansion, we focused on identifying differences in gene expression along with phenotypical transformation between proliferating and quiescent human beta cells. FACS-purified beta cells from three different human pancreata were cultured during 3-4 months (8-10 subcultures) on HTB-9 cell matrix with hepatocyte growth factor. Gene expression profiling was performed on cells from each subculture on "in-house" pancreas-specific microarrays consisting of 218 genes and concomitant morphological transformations were studied by immunocytochemistry. Immunocytochemical studies indicated a shift from epithelial to neuroepithelial cell phenotype, including progenitor cell features such as protein gene product 9.5 (PGP 9.5), Reg, vimentin, and neurogenin 3 protein expression. The expression of 49 genes was downregulated, including several markers of endocrine differentiation while 76 were induced by cell expansion including several markers of progenitor cells. Their pattern also argues for the transdifferentiation of beta cells into progenitor cells, demonstrating neuroepithelial features and overexpressing both PBX1, a homeodomain protein that can bind as a heterodimer with PDX1 and could switch the nature of its transcriptional activity, and neurogenin 3, a key factor for the generation of endocrine islet cells. Our study of the machinery that regulates human beta cell expansion and dedifferentiation may help elucidate some of the critical genes that control the formation of adult pancreatic progenitor cells and hence design targets to modify their expression in view of the production of insulin-secreting cells.

1,25-dihydroxyvitamin D3 protects RINm5F and human islet cells against cytokine-induced apoptosis: implication of the antiapoptotic protein A20.

Transplantation of islets of Langerhans is a potential cure for type 1 diabetes, but its success is hampered by destruction of the islets. The data presented herein suggest that the active metabolite of vitamin D3 [1,25-(OH)2D3] may promote islet cell survival by modulating the effects of inflammatory cytokines, which contribute to beta-cell demise. We investigated some of the mechanisms triggering the apoptotic machinery in rat insulinoma RINm5F cells and human islets treated with IL-1beta plus interferon-gamma plus TNFalpha and assessed the effects of 1,25-(OH)2D3 in these processes. Mitochondrial transmembrane permeability and apoptotic features, determined by percentage of sub-G1 cells, quantitation of DNA strand breaks, and Hoechst staining, were significantly increased by cytokines and reverted toward control values by 1,25-(OH)2D3 cotreatment. The cytoprotection of cells correlated with the abrogation of cytokine-induced nitric oxide production. The activation of nuclear factor-kappaB plays a key role in the different pathways implicated in nitric oxide generation. We demonstrated for the first time, in both RINm5F cells and human islets, that 1,25-(OH)2D3 was able to induce and maintain high levels of A20, an antiapoptotic protein known to block nuclear factor-kappaB activation. Our study showed a clear efficiency of 1,25-(OH)2D3 on the apoptotic machinery triggered by cytokines in beta-cells and suggests that 1,25-(OH)2D3 could help overcome a major obstacle encountered in the cellular therapy of diabetes, such as nonfunction in the immediate posttransplantation period.

Modulation of specific beta cell gene (re)expression during in vitro expansion of human pancreatic islet cells.

The need for transplantable beta cells with a stable phenotype has given rise to several strategies including the expansion of existing pancreatic islets and/or growth of new ones. In vitro studies of beta cell proliferation on extracellular matrices plus growth factors have highlighted a possible cell expansion technique; however, the technique was accompanied with loss of insulin secretion. Herein we showed that human islet cell proliferation was marked by a decreased expression of specific differentiation markers, particularly insulin, insulin promoting factor-1 (IPF-1), and glucokinase. After a 6-day expansion period, we tried to reexpress the beta cell differentiation markers with compounds known for their differentiation and/or insulin-secreting properties. Sodium butyrate was a potent factor of IPF-1, insulin, and glucokinase gene reexpression; it also clearly induced secretion of gastrin, a known neogenic factor. Other compounds, namely TGF-beta, calcitriol, GLP-1, and activin A, efficiently enhanced the glucose sensor machinery, particularly Glut-1 and glucokinase, thus triggering glucose responsiveness. Our results indicate that specific beta cell gene expression may be induced after expansion and dedifferentiation. This rekindles interest in human beta cell expansion. The possible stabilization of specialized genes needed by beta cells to fulfill their role as nutrient sensors and metabolic regulators may also be of interest to ensure graft maintenance and efficiency.

Comparative analysis of protein expression of three stem cell populations: models of cytokine delivery system in vivo.

Several mechanisms mediate the regenerative and reparative capacity of stem cells, including cytokine secretion; therefore these cells can act as delivery systems of therapeutic molecules. Here we begin to address the molecular and cellular basis of their regenerative potential by characterizing the proteomic profile of human embryonic stem cells (hESCs), mesenchymal stem cells (hMSCs) and marrow isolated adult multilineage inducible (MIAMI) cells, followed by analysis of the secretory profile of the latter stem cell population. Proteomic analysis establishes the closer relationship between hMSCs and MIAMI cells, while hESCs are more divergent. However, MIAMI cells appear to have more proteins in common with hESCs than hMSCs. Proteins characteristic of hMSCs include transgelin-2, phosphatidylethanolamine-binding protein 1 (PEBP1), Heat-Shock 20 kDa protein (HSP20/HSPß6), and programmed cell death 6-interacting protein (PDC6I) among others. MIAMI cells are characterized by the high level expression of ubiquitin carboxyl-terminal hydrolase isoenzyme L1 (UCHL1), 14-3-3 zeta, HSP27 (HSPß1), and tropomyosin 4 and 3. For hESC, elongation factor Tu (EFTu), isocitrate dehydrogenase (IDH1) and the peroxiredoxins 1, 2, and 6 (PRDX1, PRDX2, and PRDX6) were the most characteristic. Secretome analysis indicates that MIAMI cells secrete higher levels of vascular endothelial growth factor (VEGF), Fractalkine, Interleukin-6, interlukin-8, and growth related oncogene (GRO), compared to hMSCs. These soluble mediators are known to play key roles in angiogenesis, arteriogenesis, atheroprotection, immunomodulation, neuroprotection, axonal growth, progenitor cell migration, and prevention of apoptosis. All these roles are consistent with a reparative pro-survival secretory phenotype. We further discuss the potential of these cells as therapeutic vehicles.

Maternal hypertension induces tissue-specific modulations of the apelinergic system in the fetoplacental unit in rat.

Apelin and its receptor APJ are expressed in fetal tissues but their function and regulation remain largely unknown. In rat, maternal treatment with a nitric oxide synthase inhibitor inducing hypertension was used to investigate apelin plasma levels in mother/fetus pairs and on the gene expression level of the apelin/APJ system in fetal tissues and placenta. At term, plasma levels of apelin were not modulated but APJ expression was increased in placenta and lung but reduced in heart. Apelin expression was increased only in the heart. We postulate that the apelinergic system may control fetal growth and cardiovascular functions in utero.

Maternal malnutrition programs pancreatic islet mitochondrial dysfunction in the adult offspring.

Accumulating evidence has shown that maternal malnutrition increases the risk of metabolic disease in the progeny. We previously reported that prenatal exposure to a low-protein diet (LP) leads to mitochondrial dysfunction in pancreatic islets from adult rodent offspring that could relate physiological and cellular alterations due to early diet. We aim to determine whether mitochondrial dysfunction could be a common consequence of prenatal nutritional unbalances. Pregnant Wistar rats received either a global food restriction (GFR), consisting in the reduction by 50% of the normal daily food intake, or a high-fat diet (HF) throughout gestation. GFR or HF diet during pregnancy leads to a lack of increase in insulin release and ATP content in response to glucose stimulation in islets from 3-month-old male and female offspring. These similar consequences originated from impairment in either glucose sensing or glucose metabolism, depending on the type of early malnutrition and on the sex of the progeny. Indeed, the glucose transport across ß-cell membrane seemed compromised in female HF offspring, since GLUT-2 gene was markedly underexpressed. Additionally, for each progeny, consequences downstream the entry of glucose were also apparent. Expression of genes involved in glycolysis, TCA cycle and oxidative phosphorylations was altered in GFR and HF rats in a sex- and diet-dependent manner. Moreover, prenatal malnutrition affected the regulators of mitochondrial biogenesis, namely, PPAR coactivator 1 alpha (PGC-1α), since its expression was higher in islets from GFR rats. In conclusion, programming of mitochondrial dysfunction is a consequence of maternal malnutrition, which may predispose to glucose intolerance in the adult offspring.

Peripheral and islet interleukin-17 pathway activation characterizes human autoimmune diabetes and promotes cytokine-mediated ß-cell death.

OBJECTIVE: CD4 T-cells secreting interleukin (IL)-17 are implicated in several human autoimmune diseases, but their role in type 1 diabetes has not been defined. To address the relevance of such cells, we examined IL-17 secretion in response to ß-cell autoantigens, IL-17A gene expression in islets, and the potential functional consequences of IL-17 release for ß-cells. RESEARCH DESIGN AND METHODS: Peripheral blood CD4 T-cell responses to ß-cell autoantigens (proinsulin, insulinoma-associated protein, and GAD65 peptides) were measured by IL-17 enzyme-linked immunospot assay in patients with new-onset type 1 diabetes (n = 50). mRNA expression of IL-17A and IFNG pathway genes was studied by qRT-PCR using islets obtained from subjects who died 5 days and 10 years after diagnosis of disease, respectively, and from matched control subjects. IL-17 effects on the function of human islets, rat ß-cells, and the rat insulinoma cell line INS-1E were examined. RESULTS: A total of 27 patients (54%) showed IL-17 reactivity to one or more ß-cell peptides versus 3 of 30 (10%) control subjects (P = 0.0001). In a single case examined close to diagnosis, islet expression of IL17A, RORC, and IL22 was detected. It is noteworthy that we show that IL-17 mediates significant and reproducible enhancement of IL-1ß/interferon (IFN)-γ-induced and tumor necrosis factor (TNF)-α/IFN-γ-induced apoptosis in human islets, rat ß-cells, and INS-1E cells, in association with significant upregulation of ß-cell IL17RA expression via activation of the transcription factors STAT1 and nuclear factor (NF)-κB. CONCLUSIONS: Circulating IL-17(+) ß-cell-specific autoreactive CD4 T-cells are a feature of type 1 diabetes diagnosis. We disclose a novel pathway to ß-cell death involving IL-17 and STAT1 and NF-κB, rendering this cytokine a novel disease biomarker and potential therapeutic target.

Identification of new pancreatic beta cell targets for in vivo imaging by a systems biology approach.

Systems biology is an emergent field that aims to understand biological systems at system-level. The increasing power of genome sequencing techniques and ranges of other molecular biology techniques is enabling the accumulation of in-depth knowledge of biological systems. This growing information, properly quantified, analysed and presented, will eventually allow the establishment of a system-based cartography of different cellular populations within the organism, and of their interactions at the tissue and organ levels. It will also allow the identification of specific markers of individual cell types. Systems biology approaches to discover diagnostic markers may have an important role in diabetes. There are presently no reliable ways to quantify beta cell mass (BCM) in vivo, which hampers the understanding of the pathogenesis and natural history of diabetes, and the development of novel therapies to preserve BCM. To solve this problem, novel and specific beta cell biomarkers must be identified to enable adequate in vivo imaging by methods such as Positron Emission Tomography (PET). The ideal biomarker should allow measurements by a minimally invasive technology enabling repeated examinations over time, should identify the early stages of decreased BCM, and should provide information on progression of beta cell loss and eventual responses to agents aiming to arrest or revert beta cell loss in diabetes. The present review briefly describes the "state-of-the-art" in the field, and then proposes a step-by-step systems biology approach for the identification and initial testing of novel candidates for beta cell imaging.

Early low protein diet aggravates unbalance between antioxidant enzymes leading to islet dysfunction.

BACKGROUND: Islets from adult rat possess weak antioxidant defense leading to unbalance between superoxide dismutase (SOD) and hydrogen peroxide-inactivating enzymatic activities, catalase (CAT) and glutathione peroxidase (GPX) rending them susceptible to oxidative stress. We have shown that this vulnerability is influenced by maternal diet during gestation and lactation. METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated if low antioxidant activity in islets is already observed at birth and if maternal protein restriction influences the development of islet antioxidant defenses. Rats were fed a control diet (C group) or a low protein diet during gestation (LP) or until weaning (LPT), after which offspring received the control diet. We found that antioxidant enzymatic activities varied with age. At birth and after weaning, normal islets possessed an efficient GPX activity. However, the antioxidant capacity decreased thereafter increasing the potential vulnerability to oxidative stress. Maternal protein malnutrition changed the antioxidant enzymatic activities in islets of the progeny. At 3 months, SOD activity was increased in LP and LPT islets with no concomitant activation of CAT and GPX. This unbalance could lead to higher hydrogen peroxide production, which may concur to oxidative stress causing defective insulin gene expression due to modification of critical factors that modulate the insulin promoter. We found indeed that insulin mRNA level was reduced in both groups of malnourished offspring compared to controls. Analyzing the expression of such critical factors, we found that c-Myc expression was strongly increased in islets from both protein-restricted groups compared to controls. CONCLUSION AND SIGNIFICANCE: Modification in antioxidant activity by maternal low protein diet could predispose to pancreatic islet dysfunction later in life and provide new insights to define a molecular mechanism responsible for intrauterine programming of endocrine pancreas.

Is taurine a functional nutrient?

PURPOSE OF REVIEW: Taurine, a free amino acid, is found in millimolar concentrations in most mammalian tissues. Mammals are able to synthesize taurine endogenously, but some species such as humans are more dependent on dietary sources of taurine. A growing body of evidence suggests that taurine plays a preponderant role in many physiological processes, which will be summarized in this review. RECENT FINDINGS: Evidence for the requirement of taurine in the human diet has been obtained in many studies involving animal models and a few clinical trials. Recent and past studies suggested that taurine might be a pertinent candidate for use as a nutritional supplement to protect against oxidative stress, neurodegenerative diseases or atherosclerosis. Taurine has demonstrated promising actions in vitro, and as a result clinical trials have begun to investigate its effects on various diseases. SUMMARY: Taurine appears to have multiple functions and plays an important role in many physiological processes, such as osmoregulation, immunomodulation and bile salt formation. Taurine analogues/derivatives have recently been reported to have a marked activity on various disorders. Taken together, these observations actualize the old story of taurine.