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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 487 records · Page 27
All sourcesNASA NTRSDOE OSTI
DOE OSTI2011

Double Beta Decay Experiments

At present, neutrinoless double beta decay is perhaps the only experiment that can tell us whether the neutrino is a Dirac or a Majorana particle. Given the significance of the 0{nu}{beta}{beta}, there is a widespread interest for these rare event studies employing a variety of novel techniques. This paper describes the current status of DBD experiments. The Indian effort for an underground NDBD experiment at the upcoming INO laboratory is also presented.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2010

beta-decay properties of neutron-rich Zr and Mo isotopes

Gamow-Teller strength distributions, beta-decay half-lives, and beta-delayed neutron emission are investigated in neutron-rich Zr and Mo isotopes within a deformed quasiparticle random-phase approximation. The approach is based on a self-consistent Skyrme Hartree-Fock mean field with pairing correlations and residual separable particle-hole and particle-particle forces. Comparison with recent measurements of half-lives stresses the important role that nuclear deformation plays in the description of beta-decay properties in this mass region.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2010

Half-lives and branchings for {beta}-delayed neutron emission for neutron-rich Co-Cu isotopes in the r-process

The {beta} decays of very neutron-rich nuclides in the Co-Zn region were studied experimentally at the National Superconducting Cyclotron Laboratory using the NSCL {beta}-counting station in conjunction with the neutron detector NERO. We measured the branchings for {beta}-delayed neutron emission (P{sub n} values) for {sup 74}Co (18{+-}15%) and {sup 75-77}Ni (10{+-}2.8%, 14{+-}3.6%, and 30{+-}24%, respectively) for the first time, and remeasured the P{sub n} values of {sup 77-79}Cu, {sup 79,81}Zn, and {sup 82}Ga. For {sup 77-79}Cu and for {sup 81}Zn we obtain significantly larger P{sub n} values compared to previous work. While the new half-lives for the Ni isotopes from this experiment had been reported before, we present here in addition the first half-life measurements of {sup 75}Co (30{+-}11 ms) and {sup 80}Cu (170{sub -50}{sup +110} ms). Our results are compared with theoretical predictions, and their impact on various types of models for the astrophysical rapid neutron-capture process (r-process) is explored. We find that with our new data, the classical r-process model is better able to reproduce the A=78-80 abundance pattern inferred from the solar abundances. The new data also influence r-process models based on the neutrino-driven high-entropy winds in core collapse supernovae.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2011

Test of the conserved vector current hypothesis by a {beta}-ray angular distribution measurement in the mass-8 system

The {beta}-ray angular correlations for the spin alignments of {sup 8}Li and {sup 8}B have been observed in order to test the conserved vector current (CVC) hypothesis. The alignment correlation terms were combined with the known {beta}-{alpha} angular correlation terms to determine all the matrix elements contributing to the correlation terms. The weak magnetism term, 7.5{+-}0.2, deduced from the {beta}-ray correlation terms was consistent with the CVC prediction 7.3{+-}0.2, deduced from the analog-{gamma} decay measurement based on the CVC hypothesis. However, there was no consistent CVC prediction for the second-forbidden term associated with the weak vector current. The experimental value for the second-forbidden term was 1.0{+-}0.3, while the CVC prediction was 0.1{+-}0.4 or 2.1{+-}0.5.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2010

Inverse neutrinoless double beta decay revisited: Neutrinos, Higgs triplets, and a muon collider

We revisit the process of inverse neutrinoless double beta decay (e{sup -}e{sup -{yields}}W{sup -}W{sup -}) at future linear colliders. The cases of Majorana neutrino and Higgs triplet exchange are considered. We also discuss the processes e{sup -{mu}-{yields}}W{sup -}W{sup -} and {mu}{sup -{mu}-{yields}}W{sup -}W{sup -}, which are motivated by the possibility of muon colliders. For heavy neutrino exchange, we show that masses up to 10{sup 6} (10{sup 5}) GeV could be probed for ee and e{mu} machines, respectively. The stringent limits for mixing of heavy neutrinos with muons render {mu}{sup -{mu}-{yields}}W{sup -}W{sup -} less promising, even though this process is not constrained by limits from neutrinoless double beta decay. If Higgs triplets are responsible for inverse neutrinoless double beta decay, observable signals are only possible if a very narrow resonance is met. We also consider unitarity aspects of the process in case both Higgs triplets and neutrinos are exchanged. An exact seesaw relation connecting low energy data with heavy neutrino and triplet parameters is found.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2011

High-Precision Half-Life Measurement for the Superallowed {beta}{sup +} Emitter {sup 26}Al{sup m}

A high-precision half-life measurement for the superallowed {beta}{sup +} emitter {sup 26}Al{sup m} was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T{sub 1/2}=6346.54{+-}0.46{sub stat{+-}}0.60{sub syst} ms, consistent with, but 2.5 times more precise than, the previous world average. The {sup 26}Al{sup m} half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed {beta} decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for {sup 26}Al{sup m}, 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi {beta}-decay studies used to test the conserved vector current hypothesis and determine the V{sub ud} element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2017

Soil microbial beta-diversity is linked with compositional variation in aboveground plant biomass in a semi-arid grassland

Exploring biodiversity linkages between above-ground and below-ground biota is a core topic in ecology, and can have implications on our understanding of ecosystem process stability. Yet, this topic still remains underexplored. Here, we explored diversity linkages, in terms of both alpha- and beta- diversity, between plant and top soil microbial communities in a semi-arid grassland ecosystem. Soil microbial community structure was assessed based on both 16S rRNA and functional genes, and plant community composition was evaluated by traditional “species composition” and a newly-defined “biomass composition”, which includes the information on the biomass of each species. The bacterial alpha-diversity, expressed as the richness and Shannon diversity of 16S rRNA genes, was significantly correlated with plant species richness and Shannon diversity, whereas the alpha-diversity of microbial functional genes showed marginal association with total plant biomass. Microbial beta-diversity, evaluated by 16S rRNA genes, showed close relationship with plant beta-diversity estimated by both “species composition” and “biomass composition”, while the microbial beta-diversity based on functional genes was only associated with the compositional variation in above-ground plant biomass. These results showed that the differences in metabolic potential of soil microbial communities, which is closely related with ecosystem functions, can be better predicted by the variation of plant-derived resources returned to soil, than merely by the species composition of the macro-organism communities.

16s rRNA↗
DOE OSTI2010

Positive regulation of the Egr-1/osteopontin positive feedback loop in rat vascular smooth muscle cells by TGF-{beta}, ERK, JNK, and p38 MAPK signaling

Previous studies identified a positive feedback loop in rat vascular smooth muscle cells (VSMCs) in which early growth response factor-1 (Egr-1) binds to the osteopontin (OPN) promoter and upregulates OPN expression, and OPN upregulates Egr-1 expression via the extracellular signal-regulated protein kinase (ERK) signaling pathway. The current study examined whether transforming growth factor-{beta} (TGF-{beta}) activity contributes to Egr-1 binding to the OPN promoter, and whether other signaling pathways act downstream of OPN to regulate Egr-1 expression. ChIP assays using an anti-Egr-1 antibody showed that amplification of the OPN promoter sequence decreased in TGF-{beta} DNA enzyme-transfected VSMCs relative to control VSMCs. Treatment of VSMCs with PD98059 (ERK inhibitor), SP600125 (JNK inhibitor), or SB203580 (p38 MAPK inhibitor) significantly inhibited OPN-induced Egr-1 expression, and PD98059 treatment was associated with the most significant decrease in Egr-1 expression. OPN-stimulated VSMC cell migration was inhibited by SP600125 or SB203580, but not by PD98059. Furthermore, MTT assays showed that OPN-mediated cell proliferation was inhibited by PD98059, but not by SP600125 or SB203580. Taken together, the results of the current study show that Egr-1 binding to the OPN promoter is positively regulated by TGF-{beta}, and that the p38 MAPK, JNK, and ERK pathways are involved in OPN-mediated Egr-1 upregulation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2010

Integrin {beta}1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin {beta}1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin {beta}1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin {beta}1-dependent phenotype, and integrin {beta}1 might be a potentially effective therapeutic target in combination with radiotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Characterization of histone H3K27 modifications in the {beta}-globin locus

Research highlights: {yields} The {beta}-globin locus control region is hyperacetylated and monomethylated at histone H3K27. {yields} Highly transcribed globin genes are marked by H3K27ac, but H3K27me2 is remarkable at silent globin genes in erythroid K562 cells. {yields} Association of PRC2 subunits is comparable with H3K27me3 pattern. {yields} Modifications of histone H3K27 are established in an enhancer-dependent manner. -- Abstract: Histone H3K27 is acetylated or methylated in the environment of nuclear chromatin. Here, to characterize the modification pattern of H3K27 in locus control region (LCR) and to understand the correlation of various H3K27 modifications with transcriptional activity of genes, we analyzed the human {beta}-globin locus using the ChIP assay. The LCR of the human {beta}-globin locus was enriched by H3K27ac and H3K27me1 in erythroid K562 cells. The highly transcribed globin genes were hyperacetylated at H3K27, but the repressed globin genes were highly dimethylated at this lysine in these cells. However, in non-erythroid 293FT cells, the {beta}-globin locus was marked by a high level of H3K27me3. EZH2 and SUZ12, subunits of polycomb repressive complex 2, were comparably detected with the H3K27me3 pattern in K562 and 293FT cells. In addition, H3K27ac, H3K27me1 and H3K27me3 were established in an enhancer-dependent manner in a model minichromosomal locus containing an enhancer and its target gene. Taken together, these results show that H3K27 modifications have distinctive correlations with the chromatin state or transcription level of genes and are influenced by an enhancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

MAPK/ERK and Wnt/{beta}-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells

Highlights: {yields} Activation of MAPK/ERK pathway with epidermal growth factor (EGF) significantly increased Sca-1{sup +} HPC proliferation and colony formation. {yields} Activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. {yields} Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation and maintain long-term HPCs in vitro. -- Abstract: Hepatic progenitor cells (HPCs) persist in adulthood and have the potential to play a major role in regenerating diseased liver. However, the signaling pathways that both directly and indirectly regulate HPCs' self-renewal and differentiation remain elusive. Previously, we identified a bipotent, stem cell antigen-1 (Sca-1) positive HPC population from naive adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1{sup +} HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1{sup +} HPC proliferation and colony formation while stimulating phosphorylation of ERK1/2 and activating the induction of Cyclin D1. There were no demonstrable effects of EGF on Akt. The MEK inhibitor, PD0325901, inhibits proliferation and ERK1/2 phosphorylation while also suppressing the expression of Cyclin D1. In addition, activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. The Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation ratio and maintain long-term HPC in vitro. The data indicates that the MAPK/ERK pathway is both essential and critical for HPC proliferation, and the Wnt signaling pathway is not sufficient, while it works synergistically with the MAPK/ERK signaling pathway to promote HPC proliferation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic {beta}-cell mass

Highlights: {yields} We screened G-protein coupled receptors for imaging pancreatic. {yields} Database mining and immunohistochemistry identified GPCRs enriched in {beta}-cells. {yields} In vitro and in vivo assays were used to determine exocrine vs endocrine specificity. {yields} GPCR candidates for imaging of {beta}-cell mass are Prokineticin-1R, mGluR5, and GLP-1R. -- Abstract: A critical unmet need exists for methods to quantitatively measure endogenous pancreatic {beta}-cell mass (BCM) for the clinical evaluation of therapies to prevent or reverse loss of BCM and diabetes progression. Our objective was to identify G-protein coupled receptors (GPCRs) that are expressed with a high degree of specificity to islet {beta}-cells for receptor-targeted imaging of BCM. GPCRs enriched in pancreatic islets relative to pancreas acinar and hepatic tissue were identified using a database screen. Islet-specific expression was confirmed by human pancreas immunohistochemistry (IHC). In vitro selectivity assessment was determined from the binding and uptake of radiolabeled ligands to the rat insulinoma INS-1 832/13 cell line and isolated rat islets relative to the exocrine pancreas cell-type, PANC-1. Tail-vein injections of radioligands into rats were used to determine favorable image criteria of in vivo biodistribution to the pancreas relative to other internal organs (i.e., liver, spleen, stomach, and lungs). Database and IHC screening identified four candidate receptors for further in vitro and in vivo evaluation for PET imaging of BCM: prokineticin-1 receptor (PK-1R), metabotropic glutamate receptor type-5 (mGluR5), neuropeptide Y-2 receptor (NPY-2R), and glucagon-like peptide 1 receptor (GLP-1R). In vitro specificity ratios gave the following receptor rank order: PK-1R > GLP-1R > NPY-2R > mGluR5. The biodistribution rank order of selectivity to the pancreas was found to be PK-1R > VMAT2 {approx} GLP-1R > mGluR5. Favorable islet selectivity and biodistribution characteristics suggest several GPCRs as potential targets for PET imaging of pancreatic BCM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Glycogen synthase kinase 3-{beta} phosphorylates novel S/T-P-S/T domains in Notch1 intracellular domain and induces its nuclear localization

Highlights: Black-Right-Pointing-Pointer Novel S/T-P-S/T domains were identified in NICD. Black-Right-Pointing-Pointer Phosphorylation of NICD on the S/T-P-S/T domains induced nuclear localization. Black-Right-Pointing-Pointer GSK-3{beta} phosphorylated S and T residues in NICD S/T-P-S/T domains. -- Abstract: We identified two S/T-P-S/T domains (2122-2124, 2126-2128) inducing Notch intracellular domain (NICD) nuclear localization. The GFP-NICD (1963-2145) fusion protein deletion mutant without classical NLS was localized in the nucleus like the full length GFP-NICD. However, quadruple substitution mutant (T2122A T2124A S2126A T2128A) showed increased cytoplasmic localization. GSK-3{beta} enhanced nuclear localization and transcriptional activity of WT NICD but not of quadruple substitution mutant. In vitro kinase assays revealed that GSK-3{beta} phosphorylated S and T residues in NICD S/T-P-S/T domains. These results suggest that the novel S/T-P-S/T domain, phosphorylated by GSK-3{beta} is also involved in the nuclear localization of NICD as well as classical NLS.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Estrogen induced {beta}-1,4-galactosyltransferase 1 expression regulates proliferation of human breast cancer MCF-7 cells

Highlights: Black-Right-Pointing-Pointer We examined the regulation and biological functions of B4GALT1 expression induced by estrogen. Black-Right-Pointing-Pointer Estrogen-induced B4GALT1 expression through the direct binding of ER-{alpha} to ERE in MCF-7 cells. Black-Right-Pointing-Pointer B4GALT1 expression activates the proliferation of MCF-7 cells via its receptor function. Black-Right-Pointing-Pointer Thus, we suggest B4GALT1 as a molecular target for inhibiting breast cancer proliferation. -- Abstract: Beta 1,4-galactosyltransferase 1 (B4GALT1) synthesizes galactose {beta}-1,4-N-acetylglucosamine (Gal{beta}1-4GlcNAc) groups on N-linked sugar chains of glycoproteins, which play important roles in many biological events, including the proliferation and migration of cancer cells. A previous microarray study reported that this gene is expressed by estrogen treatment in breast cancer. In this study, we examined the regulatory mechanisms and biological functions of estrogen-induced B4GALT1 expression. Our data showed that estrogen-induced expression of B4GALT1 is localized in intracellular compartments and in the plasma membrane. In addition, B4GALT1 has an enzyme activity involved in the production of the Gal{beta}1-4GlcNAc structure. The result from a promoter assay and chromatin immunoprecipitation revealed that 3 different estrogen response elements (EREs) in the B4GALT1 promoter are critical for responsiveness to estrogen. In addition, the estrogen antagonists ICI 182,780 and ER-{alpha}-ERE binding blocker TPBM inhibit the expression of estrogen-induced B4GALT1. However, the inhibition of signal molecules relating to the extra-nuclear pathway, including the G-protein coupled receptors, Ras, and mitogen-activated protein kinases, had no inhibitory effects on B4GALT1 expression. The knock-down of the B4GALT1 gene and the inhibition of membrane B4GALT1 function resulted in the significant inhibition of estrogen-induced proliferation of MCF-7 cells. Considering these results, we propose that estrogen regulates the expression of B4GALT1 through the direct binding of ER-{alpha} to ERE and that the expressed B4GALT1 plays a crucial role in the proliferation of MCF-7 cells through its activity as a membrane receptor.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Drp1 guarding of the mitochondrial network is important for glucose-stimulated insulin secretion in pancreatic beta cells

Mitochondria form a tubular network in mammalian cells, and the mitochondrial life cycle is determined by fission, fusion and autophagy. Dynamin-related protein 1 (Drp1) has a pivotal role in these processes because it alone is able to constrict mitochondria. However, the regulation and function of Drp1 have been shown to vary between cell types. Mitochondrial morphology affects mitochondrial metabolism and function. In pancreatic beta cells mitochondrial metabolism is a key component of the glucose-induced cascade of insulin secretion. The goal of the present study was to investigate the action of Drp1 in pancreatic beta cells. For this purpose Drp1 was down-regulated by means of shDrp1 in insulin-secreting INS1 cells and mouse pancreatic islets. In INS1 cells reduced Drp1 expression resulted in diminished expression of proteins regulating mitochondrial fusion, namely mitofusin 1 and 2, and optic atrophy protein 1. Diminished mitochondrial dynamics can therefore be assumed. After down-regulation of Drp1 in INS1 cells and spread mouse islets the initially homogenous mitochondrial network characterised by a moderate level of interconnections shifted towards high heterogeneity with elongated, clustered and looped mitochondria. These morphological changes were found to correlate directly with functional alterations. Mitochondrial membrane potential and ATP generation were significantly reduced in INS1 cells after Drp1down-regulation. Finally, a significant loss of glucose-stimulated insulin secretion was demonstrated in INS1 cells and mouse pancreatic islets. In conclusion, Drp1 expression is important in pancreatic beta cells to maintain the regulation of insulin secretion. -- Highlights: •Down-regulation of Drp1 in INS1 cells reduces mitochondrial fusion protein expression. •Mitochondrial membrane potential in INS1 cells is diminished after Drp1 down-regulation. •Mitochondria become elongated after down-regulation of Drp1 in beta cells. •Down-regulation of Drp1 in islets evokes loss of glucose-stimulated insulin secretion.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Activation of the Wnt/β-catenin pathway in pancreatic beta cells during the compensatory islet hyperplasia in prediabetic mice

The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/β-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active β-catenin associated with significant increases in protein content and gene expression of β-catenin as well as of cyclins D1, D2 and c-Myc (target genes of the Wnt pathway) but not of Tcf7l2 (the transcription factor). Meanwhile, these alterations were not observed in pancreatic islets from 30 d HFD-fed mice, that do not display significant beta cell hyperplasia. These data suggest that the Wnt/β-catenin pathway is activated in pancreatic islets during prediabetes and may play a role in the induction of the compensatory beta cell hyperplasia observed at early phase of T2DM. - Highlights: • Exposure to high-fat diet for 60 days induced prediabetes and beta cell mass expansion. • Hyperplastic pancreatic islets displayed nuclear translocation of active β-catenin. • Hyperplastic islets showed increased expression of target genes of the Wnt/β-catenin pathway. • Wnt/β-catenin pathway is activated during compensatory beta cell hyperplasia in mice.

60 APPLIED LIFE SCIENCES↗