O2 Release Research Articles

Reactive pathways toward parasitic release of singlet oxygen in metal-air batteries

The superoxide disproportionation reaction is a key step in the chemistry of aprotic metal oxygen batteries that controls the peroxide formation upon discharge and opens the way for singlet oxygen release. Here we clarify the energy landscape of the disproportionation of superoxide in aprotic media catalyzed by group 1A cations. Our analysis is based on ab initio multireference computational methods and unveils the competition between the expected reactive path leading to peroxide and an unexpected reaction channel that involves the reduction of the alkaline ion. Both channels lead to the release of triplet and singlet O2. The existence of this reduction channel not only facilitates singlet oxygen release but leads to a reactive neutral solvated species that can onset parasitic chemistries due to their well-known reducing properties. Overall, we show that the application of moderate overpotentials makes both these channels accessible in aprotic batteries.

Switching Reactive Oxygen Species into Reactive Nitrogen Species by Photocleaved O2 -Released Nanoplatforms Favors Hypoxic Tumor Repression.

In various reactive oxygen species (ROS)‐based antitumor approaches (e.g., photodynamic therapy), increasing attentions are made to improve ROS level, but the short lifetime that is another decisive hurdle of ROS‐based antitumor outcomes is not even explored yet. To address it, a photocleaved O2‐released nanoplatform is constructed to release and switch ROS into reactive nitrogen species (RNS) for repressing hypoxic breast tumor. Systematic explorations validate that the nanoplatforms can attain continuous photocontrolled O2 release, alleviate hypoxia, and elevate ROS level. More significantly, the entrapped PDE5 inhibitor (PDE5‐i) in this nanoplatform can be enzymatically decomposed into nitric oxide that further combines with ROS to generate RNS, enabling the persistent antitumor effect since RNS features longer lifetime than ROS. Intriguingly, ROS conversion into RNS can help ROS to evade the hypoxia‐induced resistance to ROS‐based antitumor. Eventually, RNS production unlocks robust antitumor performances along with ROS elevation and hypoxia mitigation. Moreover, this extraordinary conversion from ROS into RNS also can act as a general method to solve the short lifetime of ROS.

In Situ Oxygen Generation Enhances the SCAP Survival in Hydrogel Constructs

Prolonged and severe hypoxia is the main cause of death of transplanted cells prior to the establishment of functional circulation. In situ generation of oxygen by oxygen-producing scaffolds—a unique solution that could produce and deliver oxygen to the adjacent cells independently of blood perfusion—has attracted considerable attention to enhance the survivability of the transplanted cells. However, the application of oxygen-generating scaffolds for facilitating cell survival in pulp-like tissue regeneration is yet to be explored. In this study, gelatin methacryloyl (GelMA)—a biocompatible scaffolding material that closely mimics the native extracellular matrix and is conducive to cell proliferation and differentiation—was used to fabricate oxygen-generating scaffolds by loading various concentrations of CaO2. The CaO2 distribution, topography, swelling, and pore size of CaO2-GelMA hydrogels were characterized in detail. The release of O2 by the scaffold and the viability, spreading, and proliferation of stem cells from apical papilla (SCAPs) encapsulated in the GelMA hydrogels with various concentrations of CaO2 under hypoxia were evaluated. In addition, cellular constructs were engineered into root canals, and cell viability within the apical, middle, and coronal portions was assessed. Our findings showed that 0.5% CaO2-GelMA was sufficient to supply in situ oxygen for maintaining the embedded SCAP viability for 1 wk. Furthermore, the 0.5% CaO2-GelMA hydrogels improved the survivability of SCAPs within the coronal portion of the engineered cellular constructs within the root canals. This work demonstrated that 0.5% CaO2-GelMA hydrogels offer a potential promising scaffold that enhances survival of the embedded SCAPs in endodontic regeneration.

Activating Both Basal Plane and Edge Sites of Layered Cobalt Oxides for Boosted Water Oxidation

AbstractLayered AxCoO2 materials built by stacking layers of CoO2 slabs and inserting alkali ions in between them have shown a promising activity of oxygen evolution reaction (OER) due to their active edge sites. However, the large basal plane areas of the CoO2 slabs show too strong adsorption energy to the reaction intermediates, which is unfavorable for the release of O2. Here, a simple cation‐exchange strategy based on Fe3+ and alkali ions is proposed to simultaneously activate both the basal plane and edge sites of AxCoO2 for the OER. X‐ray absorption spectroscopy has revealed that the Fe3+ ions deposit both on the surface and edge sites of the CoO2 slabs and enter the interlayer. The cation‐exchanged AxCoO2 electrodes show a boosted activity compared to their pristine and conventional Fe‐doped AxCoO2 counterparts. This phenomenon is mainly ascribed to the abundant edge‐sharing Co–Fe motifs at the edge sites and the charge redistribution in the basal plane sites induced by the insertion of Fe3+ ions. This work provides a novel method to fully exploit layer‐structured materials for efficient energy conversion.

Increased hemoglobin affinity for oxygen with GBT1118 improves hypoxia tolerance in sickle cell mice.

Therapeutic agents that increase the Hb affinity for oxygen (O2) could, in theory, lead to decreased O2 release from Hb and impose a hypoxic risk to tissues. In this study, GBT1118, an allosteric modifier of Hb affinity for O2, was used to assess the impact of increasing Hb affinity for O2 on brain tissue oxygenation, blood pressure, heart rate, O2 delivery, and tolerance to hypoxia in Townes transgenic sickle cell disease (SCD) mice. Brain oxygenation and O2 delivery were studied during normoxia and severe hypoxic challenges. Chronic treatment with GBT1118 increased Hb affinity for O2, reducing the Po2 for 50% HbO2 saturation (P50) in SCD mice from 31 mmHg to 18 mmHg. This treatment significantly reduced anemia, increasing hematocrit by 33%, improved cardiac output (CO), and O2 delivery and extraction. Chronically increasing Hb affinity for O2 with GBT1118 preserved cortical O2 tension during normoxia, improved cortical O2 tension during hypoxia, and increased tolerance to severe hypoxia in SCD mice. Independent of hematological changes induced by chronic treatment, a single dose of GBT1118 significantly improved tolerance to hypoxia, highlighting the benefits of increasing Hb affinity for O2 and consequently reducing sickling of RBCs in blood during hypoxia in SCD.NEW & NOTEWORTHY Chronic pharmacologically increased hemoglobin affinity for oxygen in sickle cell disease mice alleviated hematological consequences of sickle cell disease, increasing RBC half-life, hematocrit, and hemoglobin concentration, while also decreasing reticulocyte count. Additionally, chronically increased hemoglobin affinity for oxygen significantly improved survival as well as cortical tissue oxygenation in sickle cell disease mice during hypoxia, suggesting that oxygen delivery and utilization is improved by increased hemoglobin affinity for oxygen.

Geochemical Characteristics of Late Ordovician Shales in the Upper Yangtze Platform, South China: Implications for Redox Environmental Evolution

Changes to the redox environment of seawater in the Late Ordovician affect the process of organic matter enrichment and biological evolution. However, the evolution of redox and its underlying causes remain unclear. This paper analyzed the vertical variability of main, trace elements and δ34Spy from a drill core section (well ZY5) in the Upper Yangtze Platform, and described the redox conditions, paleoproductivity and paleoclimate variability recorded in shale deposits of the P. pacificus zone and M. extraordinarius zone that accumulated during Wufeng Formation. The results showed that shale from well ZY5 in Late Ordovician was deposited under oxidized water environment, and there are more strongly reducing bottom water conditions of the M. extraordinarius zone compared with the P. pacificus zone. Excess silica (SiO2(exc)) and substitution index of paleoproductivity (Y) indicated that the P. pacificus zone had higher paleoproductivity whereas the M. extraordinarius zone was lower. The high productivity level controlled O2 release in the shallow water area as well as the oxidation degree of the P. pacificus zone. The decrease of productivity and the relatively stagnant water mass of the inner Yangtze Sea controlled the formation of relatively reduced water conditions in the M. extraordinarius zone. The chemical index of alteration (CIA) results suggested that palaeoclimatic conditions changed from warm and humid to cold and dry climate from the P. pacificus to the M. extraordinarius zones in the study area. A comparative analysis of the published Fe-S-C data for the Xiushan Datianba section showed that in the P. pacificus zone of the inner Yangtze Sea, warm and humid climate conditions drove high productivity, sulphate flux and low reactive iron flux, which promoted the expansion of oxic ocean-surface waters and mid-depth euxinic waters. In the M. extraordinarius zone, the cold and dry climate with significant uplift of the Xiang’e Submarine High led to the relative sea level decline, resulting in low productivity, sulfate flux and high reactive iron flux, which promoted the expansion of the mid-depth ferruginous waters and the shrinkage of oxic ocean-surface waters. The results offered new insights into the co-evolution of continents and oceans, and explained the role of continental weathering and uplift of the Xiang’e Submarine High in the exchange of sulfate flux and nutrients in the redox environment change of inner Yangtze Sea during the Late Ordovician.

A versatile gas-generator promoting drug release and oxygen replenishment for amplifying photodynamic-chemotherapy synergetic anti-tumor effects

Excellent efficiency of combinational therapy of chemotherapy and photodynamic therapy (PDT) highly depends on the amounts of drug and oxygen in tumor tissue. However, how to cleverly promote drug release accompanied with improving oxygen concentration remains a challenge. Herein, we proposed a gas-generator that realized a high drug loading and integrated facilitation of drug release with oxygen replenishment into a single and simple system, utilizing huge cavities and mesoporous channels of hollow mesoporous silica nanoparticles (HMSNs) for encapsulating oxygen (O2) saturated perfluoropentane (PFP) droplets, indocyanine green (ICG) and doxorubicin (DOX), biocompatible polydopamine (PDA) as the gatekeepers. Under irradiation of 808 nm laser, the thermal effect of PDA caused PFP droplets occur liquid-gas phase transition that triggered the burst release of DOX and O2, finally amplifying the synergetic effects of PDT and chemotherapy both in vitro and in vivo. The influence of PFP, GSH and laser on drug release kinetic was explored through mathematical models. Notably, the mechanism of gas-generator on accelerating drug release under irradiation based on doing volume work and enhancing diffusion coefficient was clarified by researching the relation between DOX release, PFP release and temperature change. Additionally, the way of replenishing O2 did not rely on intracellular components but timely offered abundant “fuels” for producing reactive oxygen species (ROS) when compared with traditional manners. This work provides a new research strategy for boosting drug release and opens an avenue for constructing multifunctional controlled delivery systems.

Air separation via a two-step solar thermochemical cycle based on (Ba,La)xSr1-xFeO3-δ: Thermodynamic analysis

A two-step solar thermochemical cycle was considered for air separation to produce N2 based on (Ba,La)xSr1-xFeO3-δ perovskite reduction/oxidation (redox) reactions for A-site fractions of 0 ≤ x ≤ 0.2. The cycle steps encompassed (1) thermal reduction and O2 release via concentrated solar input and (2) re-oxidation with air to uptake O2 and produce high-purity N2. Thermogravimetry at temperatures between 400 and 1100 °C in atmospheres of 0.005 to 90% O2/Ar at 1 bar was performed to measure equilibrium nonstoichiometries. The compound energy formalism was applied to model redox thermodynamics for both Ba2+ and La3+ substitution. Non-linear regression was used to determine the empirical parameters based on the thermogravimetric measurements. The model was used to define partial molar reaction enthalpies and entropies and predicted equilibrium oxygen nonstoichiometry as functions of oxide stoichiometry, site fraction, temperature, and O2 partial pressure. The thermodynamic analysis showed the materials are appealing for air separation at temperatures below 800 °C.

Effect of coal ash on the performance of CuO@TiO2-Al2O3 in chemical looping with oxygen uncoupling

For the chemical looping with oxygen uncoupling (CLOU) process that fueled with coal, the release of the gaseous O2 or the mobility of the lattice oxygen can be suppressed by coal ash deposition on the surface of the oxygen carrier (OC) or weakened by the interaction between the active phase of the OC and coal ash. In this work, we aim to identify the potential effects of coal ash on the performance of CuO@TiO2-Al2O3 OC in CLOU. Over 50 redox cycles, the CO2 yield was attained in the range of 92.1%–99.6%, indicating the stable redox reactivity of the CuO@TiO2-Al2O3 OC. According to the XRD results, Ca was found to be deposited on the surface of the OC in the form of Ca2Al2SiO7. However, a close-grained ash shell was avoided to cover the surface of OC due to the continuously gaseous O2 by CuO. In addition, stable active phases (CuO and CuAl2O4) were detected in both of the fresh and used samples. Moreover, the consumption of CuO was avoided by the formation of CaSO4 and Ca2Al2SiO7. At last, the uniform distribution of Fe2O3 was detected and accumulated on the OC, which also act as the active phase of the OC.

Physico-chemical model for dopant charge state conversion during Ti:sapphire crystal growth

An original physico-chemical model is proposed that accounts for the conversion mechanism between Ti3+ and Ti4+ during Ti:sapphire crystal growth process. This model involves release of O2 from the crystal surface, which consumes aluminum vacancies. Consequently, these vacancies diffuse from the bulk crystal toward the surface, leading to the conversion of Ti4+ into Ti3+. A set of mass balance differential equations is established for these chemical species, taking into account diffusion and chemical reaction. The boundary condition for concentration of aluminum vacancies on crystal surface is given as the function of PO2 and temperature. A preliminary numerical simulation is performed to study the proposed model, using COMSOL Multiphysics® software. The obtained radial concentration distribution profiles of Ti3+ and Ti4+ are in qualitative agreement with the experimental results, showing that the proposed model has potential for further studying point defect reactions during crystal growth of ionic crystals.

Evidence for the Mn4-Yz[rad] Magnetic Interaction in Ca2+- depleted Photosystem II

The Photosystem II (PSII) water oxidation to molecular oxygen process is catalyzed by an oxygen-bridged Mn4CaO5 cluster, known as Oxygen Evolving Complex (OEC) of PSII. The Mn4CaO5 cluster undergoes periodically four one-electron oxidation steps, S0 → S1, S1 → S2, S2 → S3, S3 → S0. The O2 release takes place during the S3-[S4]-S0 transition, S4 being a transient. The intermediates of the S-state transitions are known as metalloradical intermediate states (SiYz) and involve the free radical of Tyrosine Z (Yz, TyrZ). In most metalloradical states it was established that Yz interacts magnetically with the Mn4CaO5 cluster. However, in Ca2+- depleted PSII preparations the spin-spin interaction between the Mn4O5 and Yz, during the formation of the S2Yz intermediate state was not strongly supported experimentally. In our effort to investigate the existence of the aforementioned interaction, we took advantance of the NIR sensitivity of the S2 state of Mn4 and examined whether the S2Yz EPR spectrum can be modified. Our EPR experiments, combined with the simulation analysis of the spectra show that reversible modification of the S2 EPR spectrum by NIR irradiation results in a reversible change of the Yz EPR signal shape. These observations strongly support the idea of the magnetic interaction between the Mn4 and tyrosyl radical, upon the formation of the S2Yz metalloradical state in Ca2+- depleted PSII membranes.

Photothermal Responsive Singlet Oxygen Nanocarriers for Hypoxic Cancer Cell Ablation.

Hypoxia in aggressively proliferating tumor cells has been demonstrated to restrict the efficiency of photodynamic therapy owing to its oxygen (O2 )-dependent generation of singlet oxygen (1 O2 ) from photosensitizers under light irradiation. To address this problem, we propose a small-molecule dye-based 1 O2 capturing agent, B1. B1 not only bears a near-infrared absorbing azo-boron dipyrromethene backbone, but also has 1,4-dimethylnaphthalene, which facilitates the capture of 1 O2 to form endoperoxide (B1-SO). B1-SO undergoes a reversible reaction via near-infrared photothermal stimulation, thus allowing 1 O2 release. Based on this mechanism, stable B1-SO containing micelles (B1-SO NPs) were prepared and employed as 1 O2 nanocarriers to ablate cancer cells in vitro. Taking advantage of this O2 -independent 1 O2 releasing ability, B1-SO NPs were demonstrated to have efficient cytotoxicity under near-infrared irradiation, especially in a hypoxic environment. The unique O2 -independent 1 O2 generation process of B1-SO NPs suggests they can be used as novel cancer phototherapy agents.

Photoelectrochemical Water Oxidation and Longevous Photoelectric Conversion by a Photosystem II Electrode

AbstractThe immobilization of natural photosystem II (PSII) enzyme onto an artificial electrode offers an ingenious and promising avenue for semiartificial solar energy conversion. However, this process is significantly limited by the poor stability and the short life of PSII. Here, a new prototype of a semiartificial system is reported by anchoring PSII on polyethylenimine‐coated macroporous carbon electrode with a high load. Good electronic communication is established at the biointerface of this PSII electrode, enabling excellent photoelectrochemical (PEC) water oxidation and lasting electricity generation. The maximum turnover number of 10 200 ± 1380 mol O2 per mol PSII dimer is obtained in this system at around 10 h before complete deactivation, reaching high current‐to‐O2 conversion efficiencies. The functions of PSII to release O2 both in light and dark conditions as well as for H2O2 formation are revealed. Under periodic irradiation (AM 1.5G 1 sun), this PSII electrode allows for stable mediated photocurrent output of ≈4.31 µA cm−2 after five days, which represents the most stable photoelectric performance achieved so far for PSII‐related electrodes.

Ligand Radical Mediated Water Oxidation by a Family of Copper o-Phenylene Bis-oxamidate Complexes.

Understanding the reactivity landscape for the activation of water until the formation of the O-O bond and O2 release in molecular chemistry is a decisive step in guiding the elaboration of cost-effective catalysts for the oxygen-evolving reaction (OER). Copper(II) complexes have recently caught the attention of chemists as catalysts for the 4e-/4H+ water oxidation process. While a copper(IV) intermediate has been proposed as the reactive intermediate species, no spectroscopic signature has been reported so far. Copper(III) ligand radical species have also been formulated and supported by theoretical studies. We found, herein, that the reactivity sequence for the water oxidation with a family of Copper(II) o-phenylene bis-oxamidate complexes is a function of the substitution pattern on the periphery of the aromatic ring. In-situ EPR, FTIR, and rR spectroelectrochemical studies helped to sequence the elementary electrochemical and chemical events leading toward the O2 formation selectively at the copper center. EPR and FTIR spectroelectrochemistry suggests that ligand-centered oxidations are preferred over metal-centered oxidations. rR spectroelectrochemical study revealed the accumulation of a bis-imine bound copper(II) superoxide species, as the reactive intermediate, under catalytic turnover, which provides the evidence for the O-O bond formation during OER.

Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming.

Hypoxia drives aging and promotes age-related cognition and hearing functional decline. Despite the role of erythrocytes in oxygen (O2) transport, their role in the onset of aging and age-related cognitive decline and hearing loss (HL) remains undetermined. Recent studies revealed that signaling through the erythrocyte adenosine A2B receptor (ADORA2B) promotes O2 release to counteract hypoxia at high altitude. However, nothing is known about a role for erythrocyte ADORA2B in age-related functional decline. Here, we report that loss of murine erythrocyte–specific ADORA2B (eAdora2b−/−) accelerates early onset of age-related impairments in spatial learning, memory, and hearing ability. eAdora2b-/- mice display the early aging-like cellular and molecular features including the proliferation and activation of microglia and macrophages, elevation of pro-inflammatory cytokines, and attenuation of hypoxia-induced glycolytic gene expression to counteract hypoxia in the hippocampus (HIP), cortex, or cochlea. Hypoxia sufficiently accelerates early onset of cognitive and cochlear functional decline and inflammatory response in eAdora2b−/− mice. Mechanistically, erythrocyte ADORA2B-mediated activation of AMP-activated protein kinase (AMPK) and bisphosphoglycerate mutase (BPGM) promotes hypoxic and metabolic reprogramming to enhance production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific metabolite triggering O2 delivery. Significantly, this finding led us to further discover that murine erythroblast ADORA2B and BPGM mRNA levels and erythrocyte BPGM activity are reduced during normal aging. Overall, we determined that erythrocyte ADORA2B–BPGM axis is a key component for anti-aging and anti-age–related functional decline.

Insight into the structural evolution and thermal behavior of LiNi0.8Co0.1Mn0.1O2 cathode under deep charge

By virtue of the crucial effect of the crystal structure and transition metal (TM) redox evolution on the performance of LiNixCoyMnzO2 (NCM) cathode, systematical investigation is carried out to better understand the charge mechanism upon deep charging. Based on the results of X-ray diffraction and high-resolution transmission electron microscope, phase transformations existing on particle surface are promoted by high potential because of the deeper lithium vacancies, accompanied by more substantial structure instability. Soft X-ray absorption spectroscopy indicates that Ni acts as the major contributor to charge compensation while Co displays a remarkable redox activity over the deep charge range. The elevated integrated intensity of pre-edge in O K-edge spectra reveals the extensive amount of holes formed in O 2p orbitals and the enhanced hybridization of TM 3d - O 2p orbitals. Considering the close relationship between thermal behavior and structural evolution, the tendency of phase transitions and O2 release upon heating is accelerated by voltage rise, demonstrating the aggravated instability due to deeper Li utilization. Remaining Li contents in NCM are employed to estimate the amount of oxygen released in structural transformation and its detrimental effect on stability declares Li content-dependent characteristics. Furthermore, the extended Li vacancies, higher proportion of Ni4+ and stronger orbital hybridization are considered as three factors impeding the thermal stability of the highly-delithiated NCM.

High Levels of CO2 Exchange During Synoptic‐Scale Events Introduce Large Uncertainty Into the Arctic Carbon Budget

AbstractCO2 release from thawing permafrost is both a consequence of, and a driver for, global warming, making accurate information on the Arctic carbon cycle essential for climate predictions. Eddy covariance data obtained from Bayelva (Svalbard) in 2015, using well‐established processing and quality control techniques, indicate that most of the annual net CO2 uptake is due to high CO2 flux events in winter that are associated with strong winds and probably relate to technical limitations of the gas analyzer. Emission events may relate to either (unidentified) instrumental limitations or to physical processes such as CO2 advection. Excluding the high winter uptake events yields an annual CO2 budget close to zero; whether or not these events are included can, therefore, have a considerable effect on carbon budget calculations. Further investigation will be crucial to pinpoint the factors causing these high CO2 flux events and to derive scientifically substantiated flux processing standards.

A smart O2-generating nanocarrier optimizes drug transportation comprehensively for chemotherapy improving

Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.

O2 distribution and dynamics in the rhizosphere of Phragmites australis, and implications for nutrient removal in sediments

Root-triggered microscale variations in O2 distribution in the rhizosphere of young Phragmites australis are important for nutrient removal in sediments. In this study, the micro-scale O2 dynamics and the small-scale changes of soluble reactive phosphorus (SRP) and ammonium (NH4+) in the rhizosphere of P. australis were investigated using planar optodes and high-resolution dialysis (HR-Peeper), respectively. Results suggested that root O2 leakage has a highly variable distribution depending on the stage of root growth, the site of O2 leakage gradually shift from the entire emerging main roots to the main root tip and subsequently shifted the emerging lateral roots. The O2 concentration increased in the rhizosphere with increasing light intensity and O2 levels in the overlying water. Continuous O2 release from the lateral roots causes the formation of iron plaque on the surface of lateral roots, which reduce the mobility of P by adsorption of iron plaque in the rhizosphere. The oscillation of oxic-anoxic root zones improves nitrogen removal through the processes of anammox, heterotrophic denitrification and nitrification. This work from the micro-scale demonstrates that the O2 concentration is the spatio-temporal variations in the rhizosphere, and it presents an important role for nutrient removal in sediments.

Glycerol‐3‐phosphate phosphatase/ Pgp in Pancreatic ß‐cells Functions as a Glucose Excess Security Valve Preventing Oversecretion of Insulin Secretion and Glucotoxicity

Objective The recently identified enzyme in mammalian cells, glycerol-3-phosphate (Gro3P) phosphatase (G3PP), gene name Pgp, was proposed to regulate intermediary metabolism. G3PP was shown in in vitro studies to regulate metabolism and glucose stimulated insulin secretion (GSIS) in ß-cells. We now examined the in vivo role of G3PP in the control of insulin secretion and ß-cell glucotoxicity. Methods Glucose and insulin tolerance were studied in ß-cell specific G3PP-KO (BKO) mice. Body weight gain, fed glycemia and insulinemia were measured. Pancreatic islets were isolated for ex vivo GSIS and biochemical measurements. Results BKO mice show increased body weight gain, unaltered fed glycemia and insulinemia, and enhanced insulin secretion in response to glucose load in an intraperitoneal but not oral glucose tolerance test, reaching 21 and 14 mM glucose, respectively. Insulin sensitivity in vivo remains unchanged in the BKO mice. GSIS response ex vivo at 16 mM but not 8 mM glucose is higher in BKO mouse islets. BKO islets show reduced glucose-induced glycerol release and elevated O2 consumption and ATP production at high (16 mM) but not low (4 mM) glucose levels. Glucotoxicity at 30 mM glucose for 7 days led to increased apoptosis, reduced insulin content and expression of Pdx-1 and Ins-2 genes in BKO islets. Conclusion G3PP impacts insulin secretion in vivo and ex vivo only under conditions of high but not intermediate and low glucose levels. G3PP plays a role in preventing ß-cell glucotoxicity. These effect likely result from the capacity of G3PP to redirect the excess glucose carbons from intermediate metabolism to glycerol that exits ß-cells. We propose that G3PP acts as a glucose excess security valve to prevent excessive insulin secretion and ß-cell dysfunction when blood glucose reaches very high levels.