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Taurine in Health and Disease, 2012: 167-190 ISBN: 978-81-7895-520-9
Editors: A. El Idrissi and W. L’Amoreaux
8. Taurine and metabolic disease
Svend Høime Hansen1
and Ole Hartvig Mortensen2
1Department of Clinical Biochemistry, 3-01-1, Rigshospitalet, Copenhagen University Hospital
Blegdamsvej 9, DK-2100 Copenhagen, Denmark; 2Department of Biomedical Sciences
University of Copenhagen, Blegdamsvej 3, DK-2100 Copenhagen, Denmark
1.1. Introduction
Taurine is a sulfur-containing amino acid, which does not enter protein synthesis, and is traditionally considered as an inert molecule without any reactive groups. Besides the well-known conjugation with bile acids, taurine has a number of other physiological functions such as, intracellular osmolyte for volume regulation and some antioxidant properties (Bouckenooghe et al., 2006; Hansen, 2001; Huxtable, 1992; Jacobsen and Smith, 1968; Schuller- Levis and Park, 2003). Taurine is thus not expected to be directly involved in metabolic pathways. Nevertheless, taurine deficiency in the cat results in a marked dysfunction of energy demanding tissues (i.e. retina and heart) (Sturman, 1993), and similar observations are seen in the taurine-transporter knockout mouse (Warskulat et al., 2007).
1.2. Taurine and glucose metabolism - diabetes
Taurine was first shown to have an effect upon glucose homeostasis
in the 1930s (Ackermann and Heinsen, 1935), where it was reported to have a Correspondence/Reprint request: Dr. Ole Hartvig Mortensen, Department of Biomedical Sciences, Blegdamsvej
3, DK-2200 Copenhagen, Denmark. E-mail: [email protected]; Svend Høime Hansen, Rigshospitalet
Copenhagen University Hospital, Blegdamsvej 9, Dk-2100 Copenhagen, Denmark. E-mail: [email protected]
Svend Høime Hansen & Ole Hartvig Mortensen 168
hypoglycemic effect. Since then, a lot of studies have shown a clear
interaction between taurine and diabetes, as described in recent literature
reviews (Franconi et al., 2006; Hansen, 2001; Kim et al., 2007). Several
hypotheses as to how this interplay is orchestrated have been proposed, as
taurine has shown both developmental, osmoregulatory, anti-apoptotic, anti-
inflammatory, and anti-oxidant effects as well as effects on lipid, cholesterol,
and calcium homeostasis (Della Corte et al., 2002; Franconi et al., 2004; Lee
et al., 2005; Schaffer et al., 2009).
1.2.1. Humans
In diabetic patients, taurine homeostasis is dysregulated, as type 1
diabetic patients have an increased urinary taurine excretion (Hermansson
and Mårtensson, 1984) and both type 1 and type 2 diabetic patients have a
decreased plasma taurine concentration (De Luca et al., 2001b, 2001a;
Franconi et al., 1995). Furthermore, diabetes seem to cause long term
changes in taurine homeostasis, as non-diabetic women who had gestational
diabetes, but recovered, had a lower plasma taurine concentration several
years after giving birth (Seghieri et al., 2007).
Relatively few studies have examined the effect of taurine
supplementation upon glucose homeostasis in diabetic patients or patients
predisposed for developing diabetes. Elizarova et al. found that taurine
supplementation (0.5 g twice a day for 30 days) markedly decreased the
average daily plasma glucose levels and glycosuria independently of insulin
in type 1 diabetic patients (Elizarova and Nedosugova, 1996). In direct
contradiction to this study, Chauncey et al. found no effect of taurine
supplementation (1.5 g twice a day for 4 months) upon fasting glucose or
HaemoglobinA1c (HbA1c) levels in type 2 diabetic patients (Chauncey et al.,
2003). This finding is further corroborated by another study showing no
effect of taurine supplementation (0.75 g twice a day for 8 weeks) on fasting
glucose, glucose tolerance, fasting insulin and insulin sensitivity (as
measured by euglycemic hyperinsulinemic clamp) in obese healthy subjects
with a family history of type 2 diabetes (Brøns et al., 2004). Last, taurine
supplementation (1 g three times a day for 2 weeks) of obese non-diabetic
men did not have an effect on fasting plasma glucose, but taurine did prevent
intralipid-infusion-induced insulin resistance (Xiao et al., 2008). However,
these studies suffer from different limitations in their design making their
interpretation difficult: All studies lack a control group of completely healthy
subjects who receive only taurine, two studies has a very limited
characterization of the subjects (Elizarova and Nedosugova, 1996; Chauncey
et al., 2003), and one study lacks a placebo group (Elizarova and Nedosugova,
Metabolic disease 169
1996). The study with the best design (double-blinded, randomized crossover
study) examines subjects with a predominantly normal glucose tolerance
(Brøns et al., 2004). Furthermore, in several taurine supplementation studies
examining diabetic complications, differences in fasting plasma glucose,
insulin or HbA1c after taurine supplementation were not reported (Franconi
et al., 1996; Nakamura et al., 1999). Thus, whether or not taurine
supplementation has a positive effect upon glucose homeostasis in human
diabetic patients is at present impossible to ascertain and more clinical studies
examining the effect of taurine upon glucose homeostasis in diabetic patients
are needed.
1.2.2. Animal models
Whereas taurine homeostasis seems largely unaffected in streptozotocin
induced type 1 diabetes in rats (Trachtman et al., 1992), a genetic model of
type 2 diabetes, the Zucker fatty rat, shows increased taurine excretion in
urine (Williams et al., 2005) as well as an increase in the plasma taurine
concentration (Wijekoon et al., 2004). Furthermore, in high-fructose fed rats,
a well-known model of type 2 diabetes, a decrease in plasma and liver taurine
has been observed (Nandhini et al., 2005).
Several studies have shown that taurine protects β-cells against
destruction induced by streptozotocin in rodents, with most studies showing a
glucose lowering effect of taurine (Alvarado-Vásquez et al., 2003; Odetti
et al., 2003; Di Leo et al., 2004; Song et al., 2003; Hansen, 2001). The same
protective and glucose lowering effect was seen in studies on alloxan induced
type 1 diabetes in both mice (Lim et al., 1998), rats (Gavrovskaya et al.,
2008), and rabbits (Tenner et al., 2003; Winiarska et al., 2009). However, the
exact mechanisms by which taurine protects the β-cells against destruction
and lowers plasma glucose are largely unknown, but may be related to a
general mitochondrial protective effect asserted by taurine (Han et al., 2004)
or the recently reported taurine mediated remodeling of pancreatic islets
(El Idrissi et al., 2009).
Taurine has shown a beneficial effect in several animal models of type 2
diabetes. In the Otsuka Long-Evans Tokushima Fatty (OLETF) rats and in
high-fructose fed rats, taurine increased insulin sensitivity and reduced
hyperglycemia (El Mesallamy et al., 2010; Harada et al., 2004a; Nakaya
et al., 2000; Nandhini et al., 2005). However, taurine supplementation does
not show an effect in all animal models of type 2 diabetes, as in the GK rats,
taurine supplementation had no effect on plasma glucose levels (Nishimura
et al., 2002). As in type 1 diabetes, the exact mechanism by which taurine
exerts its effects upon glucose homeostasis in type 2 diabetes is largely
Svend Høime Hansen & Ole Hartvig Mortensen 170
unknown, although the effect may be either tied together with the lipid
lowering effect of taurine (as increased plasma lipids are associated with
insulin resistance), by the effect of taurine upon insulin signaling (Nandhini
et al., 2005; Takatani et al., 2004) or by a mitochondrial protective effect, as
mitochondrial dysfunction seems to be associated with decreased insulin
secretion (Mulder and Ling, 2009; Maechler et al., 2010) and insulin
resistance (Kelley et al., 2002; Lowell and Shulman, 2005; Pagel-
Langenickel et al., 2010). It may also be possible that the effect of taurine is
mediated through its conjugation with bile acids, as a recent study showed
that tauro-ursodeoxycholic acid, a chemical chaperone and a derivative of
bile acids was found to protect against diet-induced insulin resistance by
relieving ER stress (Ozcan et al., 2006). Furthermore, taurine may also be an
important factor in regulation of the inflammatory response, as its normally
occuring derivative, taurine chloramine, is a potent anti-inflammatory agent
(Park and Schuller-Levis, 2003). Incidently, low-grade inflammation is
thought to play a key role in the development of obesity induced type 2
diabetes (Lee and Pratley, 2005).
1.2.3. The C57BL/6J mouse
The mouse strain C57BL/6J (or just B6) is one of the most widely-used
animal models for understanding metabolic diseases, especially concerning
lipid metabolism and atherosclerosis and when reporting the mouse genome,
this mouse strain was chosen as the reference strain. C57BL/6J is also very
susceptible to development of obesity and atherosclerosis when using a high
fat diet (Nishina et al., 1990, 1993; Paigen et al., 1985). Based on data from
July 2010 approximately 50% of all genetically modified mouse strains in the
Mouse Genome Informatics database (http://www.informatics.jax.org) are
based on this strain.
In the 1950s, a defect in the taurine renal reabsorption was reported for
the C57BL/6J mouse strain (Harris and Searle, 1953), and further
characterisation of the transporter defect was done in the 1970s and 1980s
(Chesney et al., 1976; Jean et al., 1984; Mandla et al., 1988; Rozen et al.,
1983). Later genetic studies have not been reported. When interpreting the
results of studies using transgenic mice, the effect of taurine is only discussed
in specific taurine supplementation studies, but taurine could play the role as
silent partner, especially for metabolic studies in transgenic models back
crossed to C57BL/6J mice. In terms of supplementation studies in C57BL/6J
mice, the taurine effects could possibly be interpreted as compensation for the
renal absorption defect. Whether or not the difference in taurine homeostasis
between mice strains is important for glucose homeostasis remains to be
Metabolic disease 171
Figure 1. Possible mechanisms by which taurine exerts its anti-diabetic effect as well
as possible target tissues. AGE) advanced glycation end products.
Determined. However there is a striking difference in glucose homeostasis
and insulin response in different mice strains as well as their responsiveness
to a high fat diet (Andrikopoulos et al., 2005; Berglund et al., 2008; Funkat
et al., 2004; Kaku et al., 1988).
1.3. Taurine and diabetic complications
A number of long-term complications typically accompany the general
metabolic dysfunction in diabetes (Hansen, 2001). Most serious for the
patients are possibly the vascular complications. Diabetic retinopathy:
Microvascular complications in the eyes lead to damage of the retina, and
thus reduced visual field or in the worst case blindness. Diabetic neuropathy:
Dysfunction of the peripheral nerves causing diverse symptoms and neural
dysfunction. Diabetic nephropathy can lead to chronic renal failure and
subsequent need for haemodialysis. Besides, some of the macrovascular
complications can be fatal, e.g. cardiomyopathy and atherosclerosis (see
below). The diabetic vascular complications have all been related to
dysfunction of the endothelium. A recent study on young male type 1
diabetes patients demonstrated that taurine supplementation can reverse the
endothelial dysfunction (Moloney et al., 2010).
Svend Høime Hansen & Ole Hartvig Mortensen 172
One of the suggested hypotheses for understanding the microvascular
diabetic late complications is based on the so-called sorbitol pathway and
subsequent osmolyte depletion hypothesis. The hypothesis is based on the
fact that high glucose levels lead to intracellular sorbitol accumulation due to
aldose reductase. Sorbitol cannot in itself be transported across the cellular
membrane, and thus more labile osmolytes like taurine or myo-inositol will
gradually be depleted from the intracellular environment. Finally, the
sorbitol-producing cells will swell due to impaired volume regulation and
dysregulation of the taurine transporter (Askwith et al., 2009; Hansen, 2001;
Stevens et al., 1993). Furthermore additional taurine depletion can be caused
by intracellular scavenging of reactive carbonyl compounds and thus
prevention of AGE formation (Hansen, 2001).
The weakness of this hypothesis based on the sorbitol accumulation and
taurine depletion is the fact that it gives no direct biochemical link to the
cellular dysfunction observed in the diabetic complications. It should be noted
Figure 2. Simplified model for development of diabetic complications. Hyper-
glycemia causes sorbitol accumulation in the aldose reductase containing cells. This
causes a gradual depletion of transportable osmolytes like taurine. Consequently, cell
volume regulation becomes dysfunctional in the tissue. The process is accompanied
by a slow intracellular depletion of taurine from the mitochondrial compartment
resulting in increasing mitochondrial dysfunction.
Metabolic disease 173
that the types of tissue and organs involved in diabetic complications are all
very energy-demanding, and when comparing the clinical manifestations of
diabetic complications with those found in patients with mitochondrial
diseases (Kisler et al., 2010), major correspondence can be found. However,
it must be reasonable to assume that a gradual taurine depletion in the
intracellular environment will be expected to be accompanied by
mitochondrial depletion of taurine. Accepting taurine as an necessary
compound for mitochondrial function (see below), either as matrix pH buffer
(Hansen et al., 2006, 2010) and/or as a requirement for mitochondrial
translation being found in mitochondrial tRNA (Suzuki et al., 2002; Schaffer
et al., 2009), taurine depletion can possibly be a direct cause of mitochondrial
dysfunction. This mitochondrial role of taurine should thus be included in the
suggested viewpoint (Brownlee, 2005) of mitochondrial dysfunction as a
possible unifying hypothesis for diabetic complications.
1.4. Taurine and lipid metabolism – obesity
1.4.1. Cholesterol catabolism and bile acids
In most physiology and biochemistry text books, taurine is mentioned
solely as a component of the bile acids. Cholesterol catabolism and
subsequent excretion from the body occurs through the bile acids as the
major metabolic pathway (se Figure 3). Cholesterol is oxidized in the liver to
cholic acid by a complex enzyme framework (Russell, 2003). Cholic acid is
subsequently conjugated with either taurine or glycine predominantly in the
hepatocyte peroxisomes (Ferdinandusse et al., 2009; Solaas et al., 2000) by
the enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT) (Falany
et al., 1994; He et al., 2003; Sfakianos et al., 2002). Species differences in the
amount of bile acids conjugated to glycine or taurine exist. Thus, in rat,
hamster, pig, and human the enzyme is capable of performing taurine as well as
glycine conjugation. In cat and rat, taurine conjugation is almost exclusively
performed, and in mouse and dog, only taurine conjugation occurs (Falany
et al., 1997; He et al., 2003; Kwakye et al., 1991; Rabin et al., 1976; Sfakianos
et al., 2002; Trautwein et al., 1999). In the rabbit only glycine conjugation has
traditionally been reported (Wildgrube et al., 1986), but findings in a more
recent study raises doubt about this fact (Hagey et al., 1998). Animal experiments in rats have demonstrated that taurine
supplementation can alleviate the consequences of a high cholesterol diet by
enhancing the excretion of bile acids, either due to enhanced activity of the
hepatic 7α-hydroxylase (Nishimura et al., 2003), enhancement by taurine of
bile acid conjugation (Sugiyama et al., 1989), and/or by inhibiting the ileal
Svend Høime Hansen & Ole Hartvig Mortensen 174
bile acid reabsorption (Nishimura et al., 2009). Similar studies have been
performed in rabbits, but as rabbits almost exclusively conjugate bile acids
with glycine, taurine supplementation studies in rabbit on cholesterol
metabolism (Balkan et al., 2002, 2004) are difficult to interpret.
Only a few human studies, all with a small number of participating
subjects (N=3-11), seem to exist on taurine supplementation, subsequent bile
acid turnover and lipid metabolism (Hepner et al., 1973; Hardison and Grundy,
1983; Sjovall, 1959; Truswell et al., 1965; Tanno et al., 1989). It seems clear
that in humans, taurine is the preferred partner in bile acid conjugation
compared with glycine, as taurine supplementation clearly increases the
taurine/glycine conjugation ratio in the studies. As the bile acids are the main
way of cholesterol excretion from the body, the relative proportions of
the taurine or glycine conjugation are of interest, as relative differences in the
Figure 3. Overview of the bile acid production, bile acid conjugation with either
glycine or taurine by the bile acid CoA:amino acid:N-acyltransferase (BAAT)
enzyme, intestinal bile acid reabsorption and partly fecal excretion.
Metabolic disease 175
reabsorption of the conjugates are expected, as the water solubility is better
for taurocholate due to the sulfonic acid group in taurine.
Taurine-conjugated bile acids are readily reabsorbed in the intestine by
an active ileal transport (Krag and Phillips, 1974), so a larger circulating bile
acid pool becomes the first result of taurine supplementation. However, it is
reasonable to assume that the reabsorption becomes down-regulated through a
feedback mechanism from the circulating bile acids as in the rat (Nishimura
et al., 2009) and then enhanced excretion of cholesterol will ensue. Alternately,
the human studies could indicate that the increased circulating levels of bile
acids (including taurocholate) would downregulate the cholesterol biosynthesis.
Furthermore, bile acids and bile acid receptors have been found to participate
in metabolic regulation. Such effects of bile acids can be found reviewed
elsewhere (Lefebvre et al., 2009; Staels et al., 2010; Trauner et al., 2010).
Finally, it should be noted that a reported stimulation by tauroconjugation on
fecal bacterial degradation of cholic acid (Van Eldere et al., 1996) could
actually cause an increase of excretion of cholic acid by taurine.
1.5. Lipid metabolism
The direct involvement of taurine in cholesterol catabolism seems to
have made the majority of taurine studies to concentrate on cholesterol levels,
lipid accumulation and atherosclerotic lesions in the vessels (Kondo et al.,
2001; Militante and Lombardini, 2004; Murakami et al., 1999). A few studies
in mouse, hamster, rat or recently quail have included quantitative
determinations of lipids and/or triglycerides in plasma, liver tissue or fat
deposition (Gandhi et al., 1992; Harada et al., 2004b; Kondo et al., 2001;
Murakami et al., 2002, 2010; Mochizuki et al., 1999; Nakaya et al., 2000;
Sethupathy et al., 2002; Tsuboyama-Kasaoka et al., 2006; Yokogoshi and
Oda, 2002; Yan et al., 1993). Generally taurine supplementation causes a
decrease in plasma lipids and triglycerides. It should specifically be noticed
that taurine supplementation could reverse obesity and increase energy
expenditure in C57BL/6J mice fed a high-fat diet (Tsuboyama-Kasaoka et al.,
2006).
A clinical study with taurine supplementation to a minor group of
overweight or obese non-diabetic subjects found a minor decrease in plasma
triglycerides, but no change in plasma cholesterol (Zhang et al., 2004). In one
study (Mochizuki et al., 1999) no effect of taurine supplementation was
found on the liver lipids, but a minor decrease was observed on liver
cholesterol. In all the other studies, taurine supplementation demonstrated a
clear decrease in lipid and triglyceride levels. Finally, an epidemiologic
Svend Høime Hansen & Ole Hartvig Mortensen 176
cohort study has shown that urinary taurine excretion (due to intake of fish
and shellfish) was inversely correlated to the risk of developing
artherosclerosis (Yamori, 2004, 2006). No explanation was presented in any
of the studies for the possible biochemical role of taurine.
As discussed in the previous section taurine supplementation must be
expected to increase the bile acid pool and thus improve bile acid-assisted
lipid transport mechanisms and associated metabolic regulation. Alternately,
taurine supplementation could be interpreted to enhance the mitochondrial
oxidation of fatty acids. Following this argumentation, the observed
improvements of lipid metabolism could be considered as support for the
recently presented hypothesis of taurine as mitochondrial matrix pH buffer.
Taurine supplementation will increase matrix pH buffering capacity and thus
stabilise the oxidative environment in the mitochondrial matrix to reduce
release of reactive oxygen species (ROS), and perhaps even more important
stabilise the very pH-dependent beta-oxidation of the fatty acids by the acyl-
CoA dehydrogenase enzymes (Hansen et al., 2006, 2010).
1.6. Taurine and fetal programming of metabolic disease
During the last two decades, it has become apparent that nutrition and
environment during pregnancy and early life have a lasting effect upon the
metabolic phenotype in adult life. The idea that there is a link between early
life conditions and subsequent disease was already discovered in the 1930s
(Smith and Kuh, 2001). However, it was not until Barker in 1986 reported a
correlation between childhood nutrition and ischemic heart disease (Barker
and Osmond, 1986) and in subsequent studies Barker and Hales during the
early 1990s coined the “thrifty phenotype” hypothesis (Hales and Barker,
1992) that the correlation was rediscovered. The hypothesis suggests that
early pre- and postnatal life is a critical period during which environmental
exposures that hinder growth will lead to an adaptation of metabolism to a
limited supply of nutrients, or other types of growth restraints. This
adaptation will contribute to increased risk for disease in adult life if
sufficient nutrients are provided. The term “fetal programming” can be used
to describe the hypothesized, yet unknown, mechanism behind the “thrifty
phenotype” hypothesis (Desai and Hales, 1997; Hales and Barker, 2001).
Several human studies have thus convincingly shown that fetal
malnutrition during pregnancy, which often leads to low birth weight or a
small for gestational age fetus, confers an increased risk of obesity, insulin
resistance, type 2 diabetes and a general low life expectancy (Jones and
Ozanne, 2009; Poulsen et al., 1997; Ravelli et al., 1999; Roseboom et al.,
2001a, 2001b). Several animal models in species ranging from rodents to
Metabolic disease 177
monkeys and of fetal malnutrition or low birth weight has been used to study
fetal programming, or intrauterine growth retardation (IUGR), with some of
the most popular ones being protein or dietary restriction during gestation,
intrauterine artery ligation and dexamethasone treatment of the pregnant dam
(Martin-Gronert and Ozanne, 2007). Human IUGR exhibit decreased taurine
levels in the fetus (Cetin et al., 1990; Economides et al., 1989), something
which is reflected in animal models of IUGR as well (Reusens et al., 1995;
Wu et al., 1998).
Taurine is considered to be an essential amino acid during development,
as the endogenous synthesis of taurine is inadequate in the fetus (Hibbard
et al., 1990). Thus, the fetus is dependent on the maternal supply of taurine.
Taurine deficiency leads to a smaller birth weight in both cats (Sturman,
1991) and rodents (Ejiri et al., 1987). The offspring of cats (which are unable
to synthesize taurine) reared on a taurine free diet, exhibit profound
developmental abnormalities, among these being: Smaller body weight,
smaller brain weight, abnormal hind leg development as well as a
degeneration or abnormal development of the retina and visual cortex
(Sturman, 1991). Furthermore, mice deficient in the taurine transporter gene
(TauT), show a smaller overall size, however no information regarding
birthweight is available (Warskulat et al., 2007). TauT knockout mice also
show defects in heart and skeletal muscle development, most likely due to
mitochondrial effects (Ito et al., 2008; Warskulat et al., 2004). In humans, a
low plasma taurine concentration in the infant has been linked to detrimental
mental development (Heird, 2004; Wharton et al., 2004), something which
has been corroborated by animal studies (Sturman, 1993). Furthermore,
taurine supplementation in mice has shown that the exact timing of taurine
supplementation during brain development influence the learning ability,
with taurine sufficiency being most important during the perinatal and
postnatal period (Suge et al., 2007). Experimental animal studies suggest that
taurine may be a marker of fetal well being (de Boo and Harding, 2007).
Several studies have documented that taurine ameliorates some of the
harmful effects that detrimental fetal programming may confer upon the
offspring in terms of the risk of developing metabolic disease and notably,
taurine is able to at least partially prevent an experimental induced decrease
in birth weight in several animal models of fetal programming. Thus, taurine
supplementation has been shown to normalize proliferation and
vascularization of the pancreas following gestational protein restriction
(Boujendar et al., 2002, 2003) and to decrease the sensitivity of the pancreas
towards cytokines (Merezak et al., 2001, 2004). In fact, taurine prevented all
changes in mRNA expression levels in the pancreas in newborns caused by
gestational protein restriction (Reusens et al., 2008). Likewise, taurine
Svend Høime Hansen & Ole Hartvig Mortensen 178
prevented a large portion of the changes in mRNA expression levels in both
skeletal muscle and liver caused by gestational protein restriction (Mortensen
et al., 2010). Interestingly these studies of the fetal gene expression profile in
both pancreas, liver and skeletal muscle suggest that the rescue effect taurine
exerts may have a mitochondrial component. This may also be important in
human development, as a reduced activity of the placental taurine
transporters has been observed in low birth weight in humans (Norberg et al.,
1998), something which may explain the low taurine concentrations in fetal
plasma often observed in this pregnancy complication (Cetin et al., 1990). A
recent study suggest that excessive taurine during gestation may also have
detrimental effects later in life, as taurine supplementation of pregnant rats
resulted in increased obesity and insulin resistance in the offspring (Hultman
et al., 2007). Collectively these studies suggest that taurine has a programming
Figure 4. The different pathways by which taurine supplementation influences fetal
programming mediated development of type 2 diabetes.
Metabolic disease 179
or rescuing effect during fetal development, perhaps via epigenetic and/or
organogenesis related mechanisms.
1.7. Taurine, mitochondrial function and metabolic disease –
the missing link?
Recently, taurine has been suggested to have an important role in the
mitochondria as it has been suggested as a pH buffer in the mitochondrial
matrix to stabilize mitochondrial beta-oxidation of fatty acids. This oxidative
process requires mildly alkaline conditions in the mitochondrial matrix with
taurine as optimal pH buffer (Hansen et al., 2006, 2010). In addition, taurine
could have a direct role in the metabolic regulation of the pyruvate
dehydrogenase (Lombardini, 1998). Besides, taurine may be required for
optimal mitochondrial protein synthesis through taurine modified tRNAs
(Suzuki et al., 2002; Schaffer et al., 2009). High mitochondrial taurine
concentrations immediately explains the pivotal requirement for taurine
during fetal development (Suzuki et al., 2002), especially for the strongly
oxidative and thus mitochondria-rich tissues like liver and skeletal muscle as
well as pancreatic -cells. Consequently, taurine deficiency either during
development or adult life may cause impaired mitochondrial oxidation, fatty
acid oxidation and altered mitochondrial protein synthesis.
The role of mitochondrial dysfunction in insulin resistance and type 2
diabetes is debated and may actually be a consequence of insulin resistance
rather than a causal factor (Abdul-Ghani and DeFronzo, 2010; Dumas et al.,
2009; Holloszy, 2009; Schiff et al., 2009; Schrauwen et al., 2010; Turner and
Heilbronn, 2008). However, many studies have found a correlation between
decreased mitochondrial function or amount, or gene expression patterns and
type 2 diabetes. In addition, a recent viewpoint (Brownlee, 2005) has
suggested mitochondrial dysfunction as a possible unifying hypothesis for
diabetic complications. Hence, taurine deficiency as seen in diabetes may
increase the mitochondrial dysfunction and/or be involved in a vicious cycle
that ultimately lead to a worsening of the diabetic condition and
mitochondrial function. Thus it will be important in to examine the TauT
knockout mice in terms of susceptibility to diet induced type 2 diabetes.
1.7.1. Therapeutic perspectives for taurine as supplementation
Several animal studies have demonstrated positive effect on cholesterol
and lipid metabolism with subsequent prevention in the development of
atherosclerosis. These studies strongly support the idea of using taurine for
alleviating impaired lipid metabolism in atherosclerosis, type 2 diabetes and
Svend Høime Hansen & Ole Hartvig Mortensen 180
obesity. The arguments for using taurine to prevent diabetic complication are
also convincing, possibly in combination with aldose reductase inhibitors, as
taurine uptake in the affected cells might be prevented due to sorbitol
accumulation, which can be prevented with these inhibitors.
Taurine is today available as supplementation or in high concentrations
in energy drinks like the Austrian brand Red Bull or the Japanese brand
Lipovitan. However, the availability as commercial consumer products also
seems to represent a hindrance for establishing health recommendations with
regards to daily intake of taurine, as the number of associated clinical
metabolism studies is very limited. Even a recent meta-analysis on the role of
taurine in development and growth from Cochrane (Verner et al, 2007) does
not include any convincing biochemical arguments.
We hope that this review encourages future research, as the therapeutic
perspectives of the presented hypotheses need to be tested.
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