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.     

Taurine-diabetes interaction: from involvement to protection

Taurine is a sulfur amino acid (2-amino ethane sulfonic acid) and has been claimed for a number of beneficial actions ranging from anti-epilepsy to anti-hypertension. Taurine in diabetes has an age old story; taurine is involved in the development and protection of insulin apparatus. Taurine and insulin both have mutual stimulating actions with hypoglycemic properties. On the clinical front, taurine supplementation has an acceptable beneficial effect in platelet aggregation and, to name few more, in neuropathy, cardiomyopathy, and nephropathy to retinopathy. Recent studies have provided a role for taurine in fetal development and in blocking the transfer of diabetes from diabetic mother to offspring. A number of mechanisms for the actions of taurine have been advocated, from osmoregulation to anti-oxidation. Though sulfonylurea and recently introduced thiazolidinediones are effective, however they are not free from complications, thus there is a need to design new therapeutics. As taurine is also a sulfonyl derivative, it will be of great interest to develop taurine analogues as an alternative therapy. Considering the great involvement of taurine in diabetes, this review may provide a holistic view of taurine in diabetes and in its prevention in this century.     

Uric Acid Levels Can Predict Metabolic Syndrome and Hypertension in Adolescents: A 10-Year Longitudinal Study

The relationships between uric acid and chronic disease risk factors such as metabolic syndrome, type 2 diabetes mellitus, and hypertension have been studied in adults. However, whether these relationships exist in adolescents is unknown. We randomly selected 8,005 subjects who were between 10 to 15 years old at baseline. Measurements of uric acid were used to predict the future occurrence of metabolic syndrome, hypertension, and type 2 diabetes. In total, 5,748 adolescents were enrolled and followed for a median of 7.2 years. Using cutoff points of uric acid for males and females (7.3 and 6.2 mg/dl, respectively), a high level of uric acid was either the second or third best predictor for hypertension in both genders (hazard ratio: 2.920 for males, 5.222 for females; p<0.05). However, uric acid levels failed to predict type 2 diabetes mellitus, and only predicted metabolic syndrome in males (hazard ratio: 1.658; p<0.05). The same results were found in multivariate adjusted analysis. In conclusion, a high level of uric acid indicated a higher likelihood of developing hypertension in both genders and metabolic syndrome in males after 10 years of follow-up. However, uric acid levels did not affect the occurrence of type 2 diabetes in both genders.     

A metabolomics approach to investigate the proceedings of mitochondrial dysfunction in rats from prediabetes to diabetes

BackgroundDiabetes mellitus (DM) is a leading cause of preventable cardiovascular disease, but the metabolic changes from prediabetes to diabetes have not been fully clarified. This study implemented a metabolomics profiling platform to investigate the variations of metabolites and to elucidate their global profiling from metabolic syndrome to DM. Methods: Male Sprague-Dawley rats (n = 44) were divided into four groups. Three groups were separately fed with a normal diet, a high-fructose diet (HF), or a high-fat (HL) diet while one group was treated with streptozotocin. The HF and HL diet were meant to induce insulin resistance, obesity, and dyslipidemia, which known to induce DM. Results: The most significant metabolic variations in the DM group’s urine samples were the reduced release of citric acid cycle intermediates, the increase in acylcarnitines, and the decrease in urea excretion, all of which indicated energy metabolism abnormalities and mitochondrial dysfunction. Overall, the metabolic analysis revealed tryptophan metabolic pathway variations in the prediabetic phase, even though the mitochondrial function remains unaffected. Conclusion: This study show that widespread methylations and impaired tryptophan metabolism occur in metabolic syndrome and are then followed by a decline in citric acid cycle intermediates, indicating mitochondrial dysfunction in diabetes.     

The role of fatty acid binding proteins in metabolic syndrome and atherosclerosis

PURPOSE OF REVIEW: The global prevalence of obesity is increasing epidemically. Obesity causes an array of health problems, reduces life expectancy, and costs over US dollar 100 billion annually. More than a quarter of the population suffers from an aggregation of co-morbidities, including obesity, atherosclerosis, insulin resistance, dyslipidemias, coagulopathies, hypertension, and a pro-inflammatory state known as the metabolic syndrome. Patients with metabolic syndrome have high risk of atherosclerosis as well as type 2 diabetes and other health problems. Like obesity, atherosclerosis has very limited therapeutic options. RECENT FINDINGS: Fatty acid binding proteins integrate metabolic and immune responses and link the inflammatory and lipid-mediated pathways that are critical in the metabolic syndrome. This review will highlight recent studies on fatty acid binding protein-deficient models and several fatty acid binding protein-mediated pathways specifically modified in macrophages, cells that are paramount to the initiation and persistence of cardiovascular lesions. SUMMARY: Adipocyte/macrophage fatty acid binding proteins, aP2 and mal1, act at the interface of metabolic and inflammatory pathways. These fatty acid binding proteins are involved in the formation of atherosclerosis predominantly through the direct modification of macrophage cholesterol trafficking and inflammatory responses. In addition to atherosclerosis, these fatty acid binding proteins also exert a dramatic impact on obesity, insulin resistance, type 2 diabetes and fatty liver disease. The creation of pharmacological agents to modify fatty acid binding protein function will provide tissue or cell-type-specific control of these lipid signaling pathways, inflammatory responses, atherosclerosis, and the other components of the metabolic syndrome, therefore offering a new class of multi-indication therapeutic agents.     

Effects of Taurine on Glial Cells Apoptosis and Taurine Transporter Expression in Retina Under Diabetic Conditions

Taurine, a ß-aminosulfonic acid, has been reported to reduce the risk of a number of diseases, including cardiovascular disease, diabetes, and also perhaps to reduce neurodegeneration in the elderly. The transport of taurine is known to be mediated by taurine transporter (TauT). The purpose of this study is to examine the effects of taurine on glial cells apoptosis and on TauT expression in retina of diabetic rats and retinal glial cells cultured with high glucose. TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining analysis showed that the number of TUNEL-positive cells in taurine treated diabetic rats was significantly lower than those of untreated diabetic rats over the 8-, and 12-week time courses, respectively (all P < 0.001). No TUNEL-positive cells were observed in retina of control groups and taurine treated control groups. In cultured retinal glial cells, the apoptosis in high glucose-treated cells was significantly increased vs the control. When the cells were incubated with high glucose and taurine at 0.1, 1.0 and 10 mmol/l, the percentage of apoptosis was significantly decreased to 16.4, 5.7 and 7.6% respectively (all P < 0.05). With supplementation of taurine in diet and culture medium, higher expression of TauT in retina of diabetic rats and cultured retinal glial cells under diabetic conditions were detected by western-blotting (P < 0.05). Taken together, our data suggest that diabetes or high glucose induced retinal glial cells apoptosis can be inhibited by taurine, and that taurine reverses the diabetes-induced or high glucose-induced decrease in TauT expression.     

The effect of taurine on cholesterol metabolism

The elevated plasma cholesterol level, in particular, LDL cholesterol is regarded as an important risk factor for the development of atherosclerosis and coronary artery disease. A number of studies provide the evidence that taurine has the efficient action to reduce plasma and liver cholesterol concentrations, especially to decrease VLDL and LDL cholesterol in hypercholesterolemia animal induced by high cholesterol diet. Cholesterol lowering effect of taurine is actually involved in the regulatory mechanism of cholesterol and bile acid homeostasis that mediated by CYP7A1, which has become a biomarker for cholesterol metabolism and itself is also regulated by several factors and nuclear receptors. This review summarizes the change of cholesterol concentration in metabolism observed in feeding studies of hypercholesterolemia animal dealing with taurine, and then, addresses the possible metabolic and molecular mechanisms of cholesterol lowering effect by taurine in three aspects, cholesterol clearance from blood circulation, bioconversion of cholesterol to bile acid in liver, and excretion of cholesterol and bile acid from intestine.     

Effect of glycine in streptozotocin-induced diabetic rats

Inadequate utilization of glucose in diabetes mellitus favors diverse metabolic alterations that play a relevant role in the physio-pathology of chronic complications of this disease. Streptozotocin-induced diabetic rats were treated daily with glycine (130 mM as optimal concentration) or taurine (40 mM) for six months. Groups of diabetic rats without treatment were used as controls. Glucose, total cholesterol, triacylglycerol, and glycated hemoglobin were determined periodically after inducing diabetes. Rats were killed after 6 months of treatment and histological analyses were performed. Diabetic groups that received glycine or taurine showed significant lower concentrations of glucose, total cholesterol, triacylglycerol, and glycated hemoglobin than diabetic control rats (P<0.05) after 6 months treatment. Histological analyses of diabetic rats showed pancreatic atrophy and necrosis, vacuolization, decrease of beta cells, and diffuse glomerulosclerosis. Diabetic rats treated with glycine or taurine showed less enlargement of the glomerular basal membrane than control diabetic rats. Our results suggest that glycine and taurine reduced the alterations induced by hyperglycemia in streptozotocin-induced diabetic rats probably due to inhibition of oxidative processes.     

Effect of dietary taurine supplementation on metabolome variation in plasma of Nile tilapia

Taurine has been considered as an essential nutrient for many aquaculture species. While dietary taurine supplementation is highly recommended, novelty studies on taurine metabolism in fish are needed. The present study aimed to provide insight into the molecular mechanisms involved in multiple metabolome changes in Nile tilapia (Oreochromis niloticus) by studying plasma metabolic profile changes in response to graded levels of dietary taurine supplementation. The analysis used proton nuclear magnetic resonance-based metabolomics. Four groups of tilapias were fed with four diets supplemented with 0.0, 0.4, 0.8 and 1.2% taurine for 84 days. Fish plasma was sampled at multiple time points to provide an accurate snapshot of specific metabolic profiles during growth. Under the effect of taurine supplementation, 21 and 12 metabolites in tilapia plasma shown significant changes in terms of time-dependence and diet-dependence, respectively. These metabolic changes in tilapia plasma were mainly associated with energy and amino acid metabolism, lipids, nucleotides and protein metabolism. The results indicate that 0.8% taurine supplementation could significantly improve the carbohydrate synthesis, protein digestion and absorption, and fat deposition of tilapia and thereby promoted growth and development of tilapia.     

Possible Contribution of Taurine to Distorted Glucagon Secretion in Intra-Islet Insulin Deficiency: A Metabolome Analysis Using a Novel α-Cell Model of Insulin-Deficient Diabetes

Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s) involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.     

Reduction of brain taurine: Effects on neurotoxic and metabolic actions of kainate

The effects of chronic administration of 2-guanidinoethane sulfonic acid on the levels of intra- and extracellular amino acids in the rat hippocampus were studied. The tissue content of taurine was selectively reduced by almost one third after 9 days of peroral administration of 1% 2-guanidinoethane sulfonate. Extracellular levels of amino acids were monitored with the brain microdialysis method. The taurine concentration in the extracellular fluid was depressed in relation to the decrease in intracellular taurine. Unexpectedly, extracellular (but not intracellular) glutamate was doubled in 2-guanidinoethane sulfonate treated animals. The kainic acid evoked release of taurine was suppressed in the 2-guanidinoethane sulfonate group, whereas the kainate stimulated efflux of glutamate was elevated after 2-guanidinoethane sulfonate administration. The acute metabolic effects of kainate were studied by measuring the efflux of the adenosine triphosphate breakdown products hypoxanthine, xanthine, inosine and adenosine. No differences were found between control and 2-guanidinoethane sulfonate treated rats with respect to basal or kainic acid evoked release of purine catabolites. Also, the neuronal loss caused by kainate injection into the hippocampus was not modified by 2-guanidinoethane sulfonate treatment, suggesting that endogenous taurine does not affect these responses. We conclude that chronic administration of 2-guanidinoethane sulfonate does not sensitize central neurons to the metabolic and toxic actions of kainate.     

Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations

Although good glycaemic control can delay the development and progression of diabetic retinopathy, new therapies are needed to obtain a better control of this diabetic complication. Oxidative stress seems to be a contributing factor in diabetic retinal alterations, therefore, it has been suggested that antioxidants may be beneficial in reducing diabetic retinal changes. However, many questions are still open. In fact, it remains to be ascertained which antioxidants are the most active when they are chronically administered in vivo and their effective dosages. Therefore, we compared the effect of chronic taurine supplementations versus a mixture of vitamin E + selenium on biochemical retinal changes induced by diabetes at different stages of the disease. Briefly, streptozotocin (STZ) diabetic rats were administered for 4 months following the dietary supplements: (a) 2% (w/w) taurine; (b) 5% (w/w) taurine; (c) 200 IU vitamin E + 8 mg selenium/kg diet (d) 500 IU vitamin E + 8 mg selenium/kg diet. In STZ diabetic rat in poor metabolic control (i.e. serum glucose >16.5 mmol/l), at 2, 4, 8, 16 weeks following the onset of diabetes, retinal conjugated dienes (CD) and lipid hydroperoxides (LP) were significantly and progressively increased, while sodium pump activity was gradually and significantly reduced. In taurine and vitamin E + selenium supplemented diabetic rats, glycaemia and body weight were not significantly different from those of non-supplemented diabetic animals. In diabetic rats, 2 and 5% taurine significantly decreased CD. This reduction is long lasting. Regarding CD, both vitamin E + selenium supplementations reduced CD only during the first 4 weeks of diabetes. Two percent taurine supplementation significantly lowered LP for the first 8 weeks of the disease while 5% taurine-induced-reduction lasted for the whole experimental time. A 200 IU vitamin E + 8 mg selenium supplementation did not significantly modify LP, while 500 IU vitamin E + 8 mg selenium significantly lowered them for the whole studied period. Finally, taurine preserved ATPase activity being more effective at 5% than 2%. Two hundred IU vitamin E + 8 mg selenium did not generally modify pump activity, while 500 IU vitamin E + 8 mg selenium partially prevented the decrease in pump activity. We conclude that taurine and vitamin E + selenium supplementations ameliorate biochemical retinal abnormalities caused by diabetes. These effects are dose- and time-dependent Moreover, the effect of taurine on CD is longer lasting than that of vitamin E + selenium. In addition, taurine seems to better preserve ATPase activity in comparison with vitamin E + selenium. Finally, in diabetic animals a negative correlation is found between CD and LP on one side and Na+K+ATPase activity on the other; thus, lipid peroxidation and pump activity seem to be associated. The same inverse correlations are present in vitamin E + selenium supplemented diabetic rats, but are lost in taurine supplemented animals. Therefore, taurine effects may not be simply mediated by its antioxidant activity. Thus, chronical (4 months) taurine and vitamin E + selenium supplementations reduce biochemical retinal alterations in diabetic rat in poor metabolic control.     

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.     

Characteristics of taurine transport system and its developmental pattern in mouse cerebral cortical neurons in primary culture

Developmental patterns and pharmacological and biochemical properties of taurine transport system were investigated using developing primary cultured neurons prepared from mouse cerebral cortex by trypsin treatment. [3H]Taurine was incorporated into neurons via a high-affinity transport system of which the Km value as well as the Vmax value increased during neuronal development in vitro. This transport system was also inhibited by sodium withdrawal from incubation medium and exposures for 15 h to several metabolic inhibitors such as 2,4-dinitrophenol and monoiodoacetate. In addition, [3H]taurine uptake in both neurons cultured for 3 and 14 days was competitively inhibited by beta-alanine, guanidinoethanesulfonate and hypotaurine. Cysteic acid and cysteine sulfinic acid, metabolic intermediates produced in the process of taurine biosynthesis in the brain from cysteine, induced significant reductions in [3H]taurine uptake in both types of cultured neurons, while cysteine, isethionic acid, cysteamine and cystamine exhibited no alterations in [3H]taurine transport. Moreover, non-competitive inhibition of [3H]taurine uptake by cysteic acid was observed in both neurons. These results clearly indicate that taurine uptake was mediated by the sodium- and energy-dependent transport system with high affinity in 14-day-old neurons as well as neurons cultured for 3 days and that both the Km and Vmax values of this transport system increase during neuronal development in vitro. The results described above suggest that the decrease in taurine content observed in developing brain is unlikely to be due to alteration in the capacity of the taurine transport system during neuronal development.     

Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD.     

Taurine increases glucose sensitivity of UCP2-overexpressing beta-cells by ameliorating mitochondrial metabolism

A low-taurine diet during fetal or early postnatal life causes abnormal pancreatic beta-cell development. Tissue and plasma taurine concentrations can also be low in diabetic patients. We examined the effect of taurine on impaired glucose responses in diabetic rat beta-cells adenovirally overexpressing uncoupling protein (UCP)2, which is upregulated in obesity-related type 2 diabetes. We found that taurine pretreatment restored the ATP-to-ADP (ATP/ADP) ratio and glucose-stimulated insulin secretion in UCP2-infected islets. ATP-sensitive K(+) channel sensitivity to dihydroxyacetone, another insulin secretagogue, was similar in both UCP2-infected and control beta-cells. In freshly isolated mitochondria from UCP2-overexpressing insulin-secreting (INS)-1 beta-cells, methyl pyruvate-mediated mitochondrial Ca(2+) increase was significantly ameliorated by taurine. A mitochondrial Ca(2+) uniporter blocker, ruthenium red, inhibited the action of taurine. This study suggests that taurine enhances the glucose sensitivity of UCP2-overexpressing beta-cells, probably by increasing mitochondrial Ca(2+) influx through the Ca(2+) uniporter, thereby enhancing mitochondrial metabolic function and increasing the ATP/ADP ratio.     

Rescue of Fructose-Induced Metabolic Syndrome by Antibiotics or Faecal Transplantation in a Rat Model of Obesity

A fructose-rich diet can induce metabolic syndrome, a combination of health disorders that increases the risk of diabetes and cardiovascular diseases. Diet is also known to alter the microbial composition of the gut, although it is not clear whether such alteration contributes to the development of metabolic syndrome. The aim of this work was to assess the possible link between the gut microbiota and the development of diet-induced metabolic syndrome in a rat model of obesity. Rats were fed either a standard or high-fructose diet. Groups of fructose-fed rats were treated with either antibiotics or faecal samples from control rats by oral gavage. Body composition, plasma metabolic parameters and markers of tissue oxidative stress were measured in all groups. A 16S DNA-sequencing approach was used to evaluate the bacterial composition of the gut of animals under different diets. The fructose-rich diet induced markers of metabolic syndrome, inflammation and oxidative stress, that were all significantly reduced when the animals were treated with antibiotic or faecal samples. The number of members of two bacterial genera, Coprococcus and Ruminococcus, was increased by the fructose-rich diet and reduced by both antibiotic and faecal treatments, pointing to a correlation between their abundance and the development of the metabolic syndrome. Our data indicate that in rats fed a fructose-rich diet the development of metabolic syndrome is directly correlated with variations of the gut content of specific bacterial taxa.     

Effect of diabetes on levels and uptake of putative amino acid neurotransmitters in rat retina and retinal pigment epithelium

Free amino acid levels and high affinity uptake of glutamate, aspartate γ-aminobutyrate, glycine and taurine were studied in retina and retinal pigment epithelium of streptozotocin diabetic rats. Results show that experimental diabetes produces a generalized fall in the content of free amino acids in both retina and retinal pigment epithelium. With regard to the high affinity uptake, in the two tissues of diabetic animals showed decreased aspartate uptake, enhanced taurine and γ-aminobutyrate uptake, whereas that of glycine and glutamate was unchanged. These results might suggest that diabetes causes alterations of specific amino acid transport systems and/or alterations of some cell populations.     

Insulin resistance and the metabolism of branched-chain amino acids in humans

Peripheral resistance to insulin action is the major mechanism causing the metabolic syndrome and eventually type 2 diabetes mellitus. The metabolic derangement associated with insulin resistance is extensive and not restricted to carbohydrates. The branched-chain amino acids (BCAAs) are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in conditions featuring insulin resistance, insulin deficiency, or both. Obesity, the metabolic syndrome and diabetes mellitus display a gradual increase in the plasma concentration of BCAAs, from the obesity-related low-grade insulin-resistant state to the severe deficiency of insulin action in diabetes ketoacidosis. Obesity-associated hyperinsulinemia succeeds in maintaining near-normal or slightly elevated plasma concentration of BCAAs, despite the insulin-resistant state. The low circulating levels of insulin and/or the deeper insulin resistance occurring in diabetes mellitus are associated with more marked elevation in the plasma concentration of BCAAs. In diabetes ketoacidosis, the increase in plasma BCAAs is striking, returning to normal when adequate metabolic control is achieved. The metabolism of BCAAs is also disturbed in other situations typically featuring insulin resistance, including kidney and liver dysfunction. However, notwithstanding the insulin-resistant state, the plasma level of BCAAs in these conditions is lower than in healthy subjects, suggesting that these organs are involved in maintaining BCAAs blood concentration. The pathogenesis of the decreased BCAAs plasma level in kidney and liver dysfunction is unclear, but a decreased afflux of these amino acids into the blood stream has been observed.     

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.