Potentiation of mitochondrial Ca2+ sequestration by taurine

Palmi, Mitri; Youmbi, Gisèle Tchuisseu; Fusi, Fabio; Sgaragli, Gian Pietro; Dixon, H. B. F.; Frosini, Maria; Tipton, Keith F.

doi:10.1016/s0006-2952(99)00183-5

Cited by 72 publications

(42 citation statements)

References 45 publications

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“…The cytosolic medium containing the isolated mitochondria for our [Ca 2ϩ ] m measurements did not contain taurine, strongly suggesting that intramitochondrial taurine participated in the methyl pyruvate-mediated [Ca 2ϩ ] m elevation in Ad-UCP2-infected mitochondria. In addition, suppression of the uniporter-mediated Ca 2ϩ influx by ruthenium red abolished the taurine effect, suggesting that taurine increases [Ca 2ϩ ] m through Ca 2ϩ uniporter activation, consistent with observations in liver (34) and neuronal (21) mitochondria. Ca 2ϩ uptake into rat liver mitochondria mediated by the high-affinity (5-20 M) Ca 2ϩ uniporter is reported to be stimulated by taurine (33) at a physiological intracellular taurine concentration (10 mM), increasing the rate almost twofold (34).…”

Section: Discussionsupporting

confidence: 88%

“…The restoring action of taurine on insulin secretion in Ad-UCP2-infected islets was not abolished even in the presence of CysA (14 Ϯ 2.4% total insulin content secreted vs. 7.6 Ϯ 1.5% in Ad-UCP2 group, P Ͻ 0.05, n ϭ 6). It was consistent with a report that CysA failed to block the enhancing effect of taurine on Ca 2ϩ sequestration into rat liver mitochondria (34). Pretreatment with CGP-37157 (10 M), a Na ϩ /Ca 2ϩ exchanger antagonist (23), also did not modify the stimulatory action of taurine on GSIS (38 Ϯ 5.1% vs. 21.6 Ϯ 3.7% in Ad-UCP2 group, P Ͻ 0.05, n ϭ 6).…”

Section: Effect Of Taurine On Methyl Pyruvate-induced Increases Insupporting

confidence: 93%

“…Thus taurine might alter the interaction of the mitochondrial Ca 2ϩ uniporter with the lipid bilayer, thereby affecting uniporter kinetic behavior (34). However, it is also possible that taurine acts directly on UCP2 activity.…”

Section: Discussionmentioning

confidence: 99%

“…An important function of taurine is to stimulate Ca 2ϩ uptake, and this has been demonstrated in cardiac sarcolemma (42) and rat retina mitochondrial membrane preparations (26). Taurine is reported to potentiate Ca 2ϩ sequestration via the Ca 2ϩ uniporter embedded on the inner membrane in mitochondria isolated from rat liver (34) and neurons (21). Because intramitochondrial Ca 2ϩ concentration ([Ca 2ϩ ] m ) has been observed to activate several dehydrogenases coupled to the Krebs or tricarboxylic acid cycle (30,39), determinants of [Ca 2ϩ ] m may be critical for controlling ␤-cell metabolic rate.…”

mentioning

confidence: 98%

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

Han¹,

Bae²,

Kim³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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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 ␤-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 ϩ channel sensitivity to dihydroxyacetone, another insulin secretagogue, was similar in both UCP2-infected and control ␤-cells. In freshly isolated mitochondria from UCP2-overexpressing insulin-secreting (INS)-1 ␤-cells, methyl pyruvate-mediated mitochondrial Ca 2ϩ increase was significantly ameliorated by taurine. A mitochondrial Ca 2ϩ uniporter blocker, ruthenium red, inhibited the action of taurine. This study suggests that taurine enhances the glucose sensitivity of UCP2-overexpressing ␤-cells, probably by increasing mitochondrial Ca 2ϩ influx through the Ca 2ϩ uniporter, thereby enhancing mitochondrial metabolic function and increasing the ATP/ADP ratio.insulin; ATP-sensitive K ϩ channel; mitochondrial Ca 2ϩ ; ATP-to-ADP ratio; pancreatic islets; uncoupling protein 2 MITOCHONDRIAL OXIDATIVE METABOLISM plays a pivotal role in the generation of signals coupling glucose recognition to insulin secretion in pancreatic ␤-cells (29). The main physiological secretagogue, glucose, is metabolized in pancreatic ␤-cells, generating NADH (38) and FADH 2 (28). Electrons donated from NADH move down the electron transport chain, causing protons to be pumped out of the mitochondrial matrix by complexes I (NADH-ubiquinone oxidoreductase), III (ubiquinone-cytochrome-c oxidoreductase), and IV (cytochrome oxidase), creating a proton electrochemical gradient. FADH 2 donates electrons to complex II. The reentry of protons through ATP synthase generates ATP from ADP (40), thus increasing the ATP-to-ADP (ATP/ADP) ratio, resulting in the closure of ATP-sensitive K ϩ (K ATP ) channels and plasma membrane depolarization. This leads to Ca 2ϩ influx through voltage-gated Ca 2ϩ channels and a rise in cytosolic Ca 2ϩ , which is the main trigger for insulin secretion (2).Prolonged exposure of ␤-cells to high glucose concentrations generates oxidative stress, resulting in ␤-cell dysfunction and ultimately cell death (47). Uncoupling protein (UCP)2 (8), a member of the mitochondrial inner membrane carrier family, catalyzes a proton leak, thereby hypopolarizing the mitochondrial membrane potential and reducing cellular ATP content (7). UCP2 expression in ␤-cells is increased by oxidative stress, suggesting that UCP2 uncoupling activity is physiologically important for ␤-cell defense against oxidants (25). However, glucose-stimulated insulin secretion (GSIS), critical for maintaining normal blood glucose levels, is suppressed when UCP2 is overexpressed in isolated islets (7) or when endogenous UCP2 is upregulated by long-term exposure (Ͼ48 h) of ␤-cells or insulin-secreting (INS)-1 ␤-cells to high glucose (36) or fr...

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Section: Discussionsupporting

confidence: 88%

Section: Effect Of Taurine On Methyl Pyruvate-induced Increases Insupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

See 2 more Smart Citations

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

Han¹,

Bae²,

Kim³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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“…Interestingly, it has been demonstrated that AEA antagonizes taurine-stimulated calcium uptake by rat liver mitochondria in a competitive fashion, suggesting the presence of a common recognition site for both compounds (Palmi et al, 1999). CAHS, which induced a taurine-like effect on body temperature, can be considered a taurine agonist.…”

Section: Discussionmentioning

confidence: 99%

A specific taurine recognition site in the rabbit brain is responsible for taurine effects on thermoregulation

Frosini

Sesti

Saponara

et al. 2003

British J Pharmacology

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1 Taurine and GABA are recognized as endogenous cryogens. In a previous study, some structural analogues of taurine, namely 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (7)cis-2-aminocyclohexane sulfonic acids (CAHS) have been shown to displace [ 3 H]taurine binding from rabbit brain synaptic membrane preparations, without interacting either with GABA-ergic systems, nor with taurine uptake mechanism, thus behaving like direct taurinergic agents. 2 To answer the question whether the role of taurine as an endogenous cryogen depends on the activation of GABA receptors or that of specific taurine receptor(s), taurine or the above structural analogues were injected intracerebroventricularly in conscious, restrained rabbits singularly or in combination and their effects on rectal (RT)-and ear -skin temperature and gross motor behavior (GMB) were monitored. 3 Taurine (1.2 Â 10 À6 -4.8 Â 10 À5 mol) induced a dose-related hypothermia, vasodilation at ear vascular bed and inhibition of GMB. CAHS, at the highest dose tested (4.8 Â 10À5 mol) induced a taurine-like effect either on RT or GMB. On the contrary ISE, injected at the same doses of taurine, induced a dose-related hyperthermia, vasoconstriction and excitation of GMB. AEA and TAG caused a dose-related hyperthermia, but at doses higher than 1.2 Â 10 À7 mol caused death within 24 h after treatment. 4 CAHS (4.8 Â 10 À5 mol) antagonized the hyperthermic effect induced by TAG (1.2 Â 10 À6 mol), AEA (1.2 Â 10 À8 mol) or ISE (4.8 Â 10 À5 mol). 5 In conclusion, these findings may indicate the existence of a recognition site specific for taurine, responsible for its effects on thermoregulation.

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Taurine rescues pancreatic β‐cell stress by stimulating α‐cell transdifferentiation

Sarnobat

Moffett

et al. 2023

BioFactors

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The semi-essential ubiquitous amino acid taurine has been shown to alleviate obesity and hyperglycemia in humans; however, the pathways underlying the antidiabetic actions have not been characterized. We explored the effect of chronic taurine exposure on cell biology of pancreatic islets, in degenerative type 1-like diabetes. The latter was modeled by small dose of streptozotocin (STZ) injection for 5 days in mice, followed by a 10-day administration of taurine (2% w/v, orally) in the drinking water. Taurine treatment opposed the detrimental changes in islet morphology and β-/α-cell ratio, induced by STZ diabetes, coincidentally with a significant 3.9 ± 0.7-fold enhancement of proliferation and 40 ± 5% reduction of apoptosis in β-cells. In line with these findings, the treatment counteracted an upregulation of antioxidant (Sod1, Sod2, Cat, Gpx1) and downregulation of islet expansion (Ngn3, Itgb1) genes induced by STZ, in a pancreatic β-cell line. At the same time, taurine enhanced the transdifferentiation of α-cells into β-cells by 2.3 ± 0.8-fold, echoed in strong non-metabolic elevation of cytosolic Ca 2+ levels in pancreatic α-cells. Our data suggest a bimodal effect of dietary taurine on islet β-cell biology, which combines the augmentation of α-/β-cell transdifferentiation with downregulation of apoptosis. The dualism of action, stemming presumably from the intra-and extracellular modality of the signal, is likely to explain the antidiabetic potential of taurine supplementation.

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Potentiation of mitochondrial Ca2+ sequestration by taurine

Cited by 72 publications

References 45 publications

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

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

A specific taurine recognition site in the rabbit brain is responsible for taurine effects on thermoregulation

Taurine rescues pancreatic β‐cell stress by stimulating α‐cell transdifferentiation

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