The potential usefulness of taurine on diabetes mellitus and its complications

Taurine (2-aminoethanesulfonic acid) is a free amino acid found ubiquitously in millimolar concentrations in all mammalian tissues. Taurine exerts a variety of biological actions, including antioxidation, modulation of ion movement, osmoregulation, modulation of neurotransmitters, and conjugation of bile acids, which may maintain physiological homeostasis. Recently, data is accumulating that show the effectiveness of taurine against diabetes mellitus, insulin resistance and its complications, including retinopathy, nephropathy, neuropathy, atherosclerosis and cardiomyopathy, independent of hypoglycemic effect in several animal models. The useful effects appear due to the multiple actions of taurine on cellular functions. This review summarizes the beneficial effects of taurine supplementation on diabetes mellitus and the molecular mechanisms underlying its effectiveness.     

Potential role of taurine in the prevention of diabetes and metabolic syndrome

Metabolic syndrome is characterized by the cluster of a number of metabolic abnormalities in the presence of underlying insulin resistance. The prevalence of metabolic syndrome has steadily increased in all populations worldwide. Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid that is involved in a variety of physiological functions. Clinical and experimental studies show that taurine intake may be beneficial in the prevention of metabolic syndrome including diabetes, obesity, dyslipidemia, and hypertension. This article reviews the effect of taurine on all of the components of metabolic syndrome. In addition, the possible mechanisms by which taurine prevents diabetes and metabolic syndrome are also discussed. Further study is needed to determine the role of taurine in the development of metabolic syndrome in humans, because there is presently limited clinical data available.     

The effect of taurine on chronic heart failure: actions of taurine against catecholamine and angiotensin II

Taurine, a ubiquitous endogenous sulfur-containing amino acid, possesses numerous pharmacological and physiological actions, including antioxidant activity, modulation of calcium homeostasis and antiapoptotic effects. There is mounting evidence supporting the utility of taurine as a pharmacological agent against heart disease, including chronic heart failure (CHF). In the past decade, angiotensin II blockade and β-adrenergic inhibition have served as the mainstay in the treatment of CHF. Both groups of pharmaceutical agents decrease mortality and improve the quality of life, a testament to the critical role of the sympathetic nervous system and the renin--angiotensin system in the development of CHF. Taurine has also attracted attention because it has beneficial actions in CHF, in part by its demonstrated inhibition of the harmful actions of the neurohumoral factors. In this review, we summarize the beneficial actions of taurine in CHF, focusing on its antagonism of the catecholamines and angiotensin II.     

Taurine attenuates hypertension and improves insulin sensitivity in the fructose-fed rat, an animal model of insulin resistance

Fructose feeding induces moderate increases in blood pressure levels in normal rats, which is associated with hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Increased vascular resistance, sodium retention, and sympathetic overactivity have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid, has been reported to have antihypertensive and sympatholytic actions. In the present study, the effects of taurine on blood pressure, plasma levels of glucose and insulin, glucose tolerance, and renal function were studied in fructose-fed rats. Fructose-fed rats had higher blood pressure and elevated plasma levels of insulin and glucose. The plasma glucose levels were higher in fructose-fed rats than in controls at 15, 30, and 60 min after the oral glucose load. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and attenuated the hyperinsulinemia in fructose-fed rats. The exaggerated glucose levels in response to the oral glucose load was also prevented by taurine administration. Thus, taurine supplementation could be beneficial in circumventing metabolic alterations in insulin resistance.     

Is Taurine Beneficial in Reducing Risk Factors for Diabetes Mellitus?

Taurine is a semiessential amino acid, and its deficiency is involved in retinal and cardiac degenerations. In recent years, it was found that diabetes mellitus (DM) is associated with taurine, and many in vivo experimental studies showed that taurine administration is able to reduce the alterations induced by DM in the retina, lens, and peripheral nerve, although its effects on diabetic kidney are dubious. Interestingly, long-term taurine supplementation reduces the mortality rate in diabetic rats. The mechanisms by which taurine exerts beneficial effects in DM are discussed below. Recently, it has been suggested that taurine deficiency may alter the endocrine pancreas "fetal programming," increasing the risk of insulin resistance in adult life. The bulk of experimental data suggests that taurine administration could be useful in the treatment of type 1 DM and in the prevention of insulin resistance.     

牛磺酸与生长发育

<正> 牛磺酸的发现已有160多年的历史,但其生物学功能在发现它的缺乏而致失明以后,其研究才迅速发展。近10年来,连续召开了8次有关牛磺酸作用的专题国际会议。研究表明,牛磺酸具有广泛的营养作用,尤其在心血管系统、中枢神经等方面具有重要的调节作用,其缺乏可引起多种疾病。例如婴儿早期缺乏可以引起生长发育的微细变化,最终导致学习、行为等方面障     

Perinatal taurine exposure affects adult arterial pressure control

Taurine is an abundant, free amino acid found in mammalian cells that contributes to many physiologic functions from that of a simple cell osmolyte to a programmer of adult health and disease. Taurine’s contribution extends from conception throughout life, but its most critical exposure period is during perinatal life. In adults, taurine supplementation prevents or alleviates cardiovascular disease and related complications. In contrast, low taurine consumption coincides with increased risk of cardiovascular disease, obesity and type II diabetes. This review focuses on the effects that altered perinatal taurine exposure has on long-term mechanisms that control adult arterial blood pressure and could thereby contribute to arterial hypertension through its ability to program these cardiovascular regulatory mechanisms very early in life. The modifications of these mechanisms can last a lifetime and transfer to the next generation, suggesting that epigenetic mechanisms underlie the changes. The ability of perinatal taurine exposure to influence arterial pressure control mechanisms and hypertension in adult life appears to involve the regulation of growth and development, the central and autonomic nervous system, the renin–angiotensin system, glucose–insulin interaction and changes to heart, blood vessels and kidney function.     

Taurine modulates kallikrein activity and glucose metabolism in insulin resistant rats

Summary. Taurine, a potent antioxidant has been reported to show an antidiabetic effect in streptozotocin-induced diabetes mellitus in which the development of hyperglycemia results from the damage to β cells of pancreas by reactive oxygen species. In addition, taurine also increases the excretion of nitrite and enhances the formation of kinins and would be expected to improve insulin resistance. The effect of taurine on insulin sensitivity was examined in the high fructose-fed rats, an animal model of insulin resistance. Male Wistar rats of body weight 170–190 g were divided into 4 groups: a control group and taurine-supplemented control group, taurine supplemented and unsupplemented fructose-fed group. An intravenous glucose tolerance test (IVGTT) and a steady state plasma glucose level (SSPG) were performed before the sacrifice. The fructose-fed rats displayed hyperglycemia and insulin resistance and they had a greater accumulation of glycogen than did control rats. Hyperglycemia and insulin resistance were significantly lower in the taurine supplemented fructose-fed group than in the unsupplemented fructose-fed group. Urinary kallikrein activity was higher in taurine-treated animals than in the rats fed only fructose. The activity of membrane bound ATPases were significantly lower in fructose-fed rats than in the control rats and were significantly higher in the taurine supplemented group than in the fructose-fed group. Taurine effectively improves glucose metabolism in fructose-fed rats presumably via improved insulin action and glucose tolerance. Received January 5, 2001 Accepted August 21, 2001     

Taurine regulates insulin release from pancreatic beta cell lines

Background

Pancreatic β-cells release insulin via an electrogenic response triggered by an increase in plasma glucose concentrations. The critical plasma glucose concentration has been determined to be ~3 mM, at which time both insulin and GABA are released from pancreatic β-cells. Taurine, a β-sulfonic acid, may be transported into cells to balance osmotic pressure. The taurine transporter (TauT) has been described in pancreatic tissue, but the function of taurine in insulin release has not been established. Uptake of taurine by pancreatic β-cells may alter membrane potential and have an effect on ion currents. If taurine uptake does alter β-cell current, it might have an effect on exocytosis of cytoplasmic vesicle. We wished to test the effect of taurine on regulating release of insulin from the pancreatic β-cell.

Methods

Pancreatic β-cell lines Hit-TI5 (Syrian hamster) and Rin-m (rat insulinoma) were used in these studies. Cells were grown to an 80% confluence on uncoated cover glass in RPMI media containing 10% fetal horse serum. The cells were then adapted to a serum-free, glucose free environment for 24 hours. At that time, the cells were treated with either 1 mM glucose, 1 mM taurine, 1 mM glucose + 1 mM taurine, 3 mM glucose, or 3 mM glucose + 1 mM taurine. The cells were examined by confocal microscopy for cytoplasmic levels of insulin.

Results

In both cell lines, 1 mM glucose had no effect on insulin levels and served as a control. Cells starved of glucose had a significant reduction (p<0.001) in the level of insulin, but this level was significantly higher than all other treatments. As expected, the 3 mM glucose treatment resulted in a statistically lower (p<0.001) insulin level than control cells. Interestingly, 1 mM taurine also resulted in a statistically lower level of insulin (p<0.001) compared to controls when either no glucose or 1 mM glucose was present. Cells treated with 1 mM taurine plus 3 mM glucose showed a level of insulin similar to that of 3 mM glucose alone.

Conclusions

Taurine administration can alter the electrogenic response in β-cell lines, leading to a change in calcium homeostasis and a subsequent decrease in intracellular insulin levels. The consequence of these actions could represent a method of increasing plasma insulin levels leading to a decrease in plasma glucose levels.

     

Hoe 140 abolishes the blood pressure lowering effect of taurine in high fructose-fed rats

Summary. High fructose feeding induces moderate increases in blood pressure of normal rats, associated with hyperinsulinemia, insulin resistance and impaired glucose tolerance. Increased vascular resistance, and sodium retention have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid has been reported to have antihypertensive and antinatriuretic actions. In addition, taurine is shown to increase the excretion of nitrite and kinin availability and hence would be expected to improve the vascular tone. In the present study, the involvement of kinins in the blood pressure lowering effect of taurine was investigated by coadministration of Hoe 140, a kinin B₂ receptor antagonist along with taurine. The effects of taurine on plasma and urinary concentrations of sodium and tissue kallikrein activity were studied in high fructose-fed rats. Fructose-fed rats had elevated blood pressure and decreased levels of sodium in urine. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and coadministration of Hoe 140 abolished this effect of taurine in high fructose-fed rats. The findings confirm the antinatriuretic action of taurine and also suggest a role for the kinins in the mechanism of taurine action in diet-induced hypertension.     

Physiological roles of taurine in heart and muscle

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca²⁺ transporters and the modulation Ca²⁺ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals.     

Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain

Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems.     

Taurine and Its Chloramine: Modulators of Immunity

Taurine is a semiessential amino acid that is not incorporated into proteins. In mammalian tissues, taurine is ubiquitous and is the most abundant free amino acid in the heart, retina, skeletal muscle, and leukocytes. Taurine reaches up to 50 mM concentration in leukocytes. Taurine has been shown to be tissue-protective in many models of oxidant-induced injury. One possibility is that taurine reacts with HOCl, produced by the myeloperoxidase (MPO) pathway, to produce the more stable but less toxic taurine chloramine (Tau-Cl). However, data from several laboratories demonstrate that Tau-Cl is a powerful regulator of the immune system. Specifically, Tau-Cl has been shown to downregulate the production of proinflammatory mediators in both rodent and human leukocytes. Recent molecular studies on the function of taurine provide evidence that taurine is a constituent of biological macromolecules. Specifically, two novel taurine-containing modified uridines have been found in both human and bovine mitrochondria. In studies on mechanism of action, Tau-Cl inhibits the activation of NFkappaB, a potent signal transducer for inflammatory cytokines, by oxidation of IkappaB alpha at methionine45. Taurine transporter knockout mice show reduced taurine, reduced fertility, and loss of vision resulting from severe retinal degeneration, which was found to be due to apoptosis. Apoptosis induced by amino chloramines is a current and important finding because oxidants derived from leukocytes play a key role in killing pathogens. The fundamental importance of taurine in adaptive and acquired immunity will be revealed using genetic manipulation.     

Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice

Taurine, a sulfur-containing β-amino acid, is highly contained in heart and skeletal muscle. Taurine has a variety of biological actions, such as ion movement, calcium handling and cytoprotection in the cardiac and skeletal muscles. Meanwhile, taurine deficiency leads various pathologies, including dilated cardiomyopathy, in cat and fox. However, the essential role of taurine depletion on pathogenesis has not been fully clarified. To address the physiological role of taurine in mammalian tissues, taurine transporter-(TauT-) knockout models were recently generated. TauTKO mice exhibited loss of body weight, abnormal cardiac function and the reduced exercise capacity with tissue taurine depletion. In this chapter, we summarize pathological profile and histological feature of heart and skeletal muscle in TauTKO mice.     

Taurine and Skeletal Muscle Disorders

Taurine is abundantly present in skeletal muscle. We give evidence that this amino acid exerts both short-term and long-term actions in the control of ion channel function and calcium homeostasis in striated fibers. Short-term actions can be estimated as the ability of this amino acid to acutely modulate both ion channel gating and the function of the structures involved in calcium handling. Long-term effects can be disclosed in situations of tissue taurine depletion and are likely related to the ability of the intracellular taurine to control transducing pathways as well as homeostatic and osmotic equilibrium in the tissue. The two activities are strictly linked because the intracellular level of taurine modulates the sensitivity of skeletal muscle to the exogenous application of taurine. Myopathies in which ion channels are directly or indirectly involved, as well as inherited or acquired pathologies characterized by metabolic alterations and change in calcium homeostasis, are often correlated with change in muscle taurine concentration and consequently with an enhanced therapeutic activity of this amino acid. We discuss both in vivo and in vitro evidence that taurine, through its ability to control sarcolemmal excitability and muscle contractility, can prove beneficial effects in many muscle dysfunctions.     

Insulin-stimulated taurine uptake in rat retina and retinal pigment epithelium.

Taurine is found at millimolar concentration in the retina and retinal pigment epithelium. High concentrations of taurine are essential for maintenance of retinal function. Taurine uptake by retina and retinal pigment epithelium was significantly enhanced by physiological concentrations of insulin as well as by high glucose concentrations. The results indicate that both, glucose and insulin enhanced taurine uptake occur through an increase in transport capacity which offset an additional, small decrease in affinity of the taurine carrier. Similar results were observed in retina and retinal pigment epithelium from streptozotocin-induced diabetic rats, suggesting that glucose and insulin regulate the taurine carrier through the same mechanism.     

The effect of taurine on renal ischemia/reperfusion injury

Summary. Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine. Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration appears to reduce the injurious effects of I/R on kidney.     

Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects

Summary. Taurine has beneficial effects on lipid metabolism in experimental animals fed with high-cholesterol or high fat diets. Whether taurine benefits lipid metabolism in humans has rarely been investigated. The aim of this study was to evaluate the effects of taurine on serum lipids in overweight or obese young adults. Thirty college students (age: 20.3±1.7 years) with a body mass index (BMI) 25.0kg/m², and with no evidence of diabetes mellitus were selected and assigned to either the taurine group (n=15) or the placebo group (n=15) by double-blind randomization. Taurine 3g/day or placebo was taken orally for 7 weeks. Triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and plasma glucose were measured before and after supplementation. The atherogenic index (AI) was calculated as (TC–HDL-C)/HDL-C. There were no differences in any baseline parameter between the two groups. Taurine supplementation decreased TG and AI significantly. Body weight also reduced significantly in the taurine group. These results suggest that taurine produces a beneficial effect on lipid metabolism and may have an important role in cardiovascular disease prevention in overweight or obese subjects.     

Mechanisms underlying taurine-mediated alterations in membrane function

Summary Taurine mediates a plethora of membrane-linked effects in excitable tissues. To account for these multiple actions, four hypotheses have been proposed. One theory is based on the observation that taurine diminishes the inflammatory response of several cytotoxic oxidants. It is proposed that a reduction in the extent of membrane oxidative injury contributes to these cytoprotective actions. The second theory maintains that alterations in protein phosphorylation may underlie certain effects of taurine, particularly its effect on calcium transport. The third hypothesis assumes that the interaction of taurine with the neutral phospholipids leads to altered membrane calcium binding and function. The final theory ties the actions of taurine to inhibition of phospholipid N-methylation and the resulting changes in membrane composition and structure. While each of these hypotheses has merit, none of them can fully explain the membrane actions of taurine. Further studies are required to ascertain the importance of each theory.     

Cellular uptake of taurine by lactating porcine mammary tissue

Milk taurine plays a critical role in neonatal development. Taurine uptake in lactating sow mammary tissue has not been characterized previously. The kinetic properties, ion dependence and substrate specificity of taurine uptake were characterized in mammary tissue collected from lactating sows at slaughter. Tissue explants were incubated in an isosmotic physiologic buffer with [³H]taurine tracer to measure taurine uptake. Taurine uptake was dependent upon the presence of extracellular sodium and chloride ions, which is consistent with the co-transport of sodium and chloride with taurine. Uptake was not dependent upon ion exchange mechanisms or upon furosemide-sensitive ion co-transport. Taurine uptake was saturable and exhibited an apparent K_m of 20 μM and a V_max of 386 μmol/kg cell water/30 min. Substrate specificity studies indicated a strong interaction of β-amino acids with the taurine transport system. Taurine transport in lactating sow mammary tissue is therefore a high affinity, sodium-dependent mechanism specific for β-amino acids, and is analogous to sodium-dependent taurine uptake in other tissues. The high affinity and high specificity of the taurine uptake system allows for concentration of taurine within the mammary cell and is ultimately responsible for provision of taurine required for neonatal development.