Spectroscopy of colloidal semiconductor core/shell nanoplatelets with high quantum yield.

Free standing two-dimensional materials appear as a novel class of structures. Recently, the first colloidal two-dimensional heterostructures have been synthesized. These core/shell nanoplatelets are the first step toward colloidal quantum wells. Here, we study in detail the spectroscopic properties of this novel generation of colloidal nanoparticles. We show that core/shell CdSe/CdZnS nanoplatelets with 80% quantum yield can be obtained. The emission time trace of single core/shell nanoplatelets exhibits reduced blinking compared to core nanoplatelets with a two level emission time trace. At cryogenic temperatures, these nanoplatelets have a quantum yield close to 100% and a stable emission time trace. A solution of core/shell nanoplatelets has emission spectra with a full width half-maximum close to 20 nm, a value much lower than corresponding spherical or rod-shaped heterostructures. Using single particle spectroscopy, we show that the broadening of the emission spectra upon the shell deposition is not due to dispersity between particles but is related to an intrinsic increased exciton-phonon coupling in the shell. We also demonstrate that optical spectroscopy is a relevant tool to investigate the presence of traps induced by shell deposition. The spectroscopic properties of the core/shell nanoplatelets presented here strongly suggest that this new generation of objects will be an interesting alternative to spherical or rod-shaped nanocrystals.

Electron cotunneling transport in gold nanocrystal arrays.

We describe current-voltage (I-V) characteristics of alkyl-ligated gold nanocrystals ~5 nm arrays in a long screening length limit. Arrays with different alkyl ligand lengths have been prepared to tune the electronic tunnel coupling between the nanocrystals. For long ligands, electronic diffusion occurs through sequential tunneling and follows activated laws, as a function of temperature σ∝e(-T(0)/T) and as a function of electric field I∝e(-E(0)/E). For better conducting arrays, i.e., with small ligands, the transport properties cross over to the cotunneling regime and follow Efros-Shklovskii laws as a function of temperature σ∝e(-(T(ES)/T)(1/2) and as a function of electric field I∝e(-(E)(ES)/E)(1/2). The data show that electronic transport in nanocrystal arrays can be tuned from the sequential tunneling to the cotunneling regime by increasing the tunnel barrier transparency.

Increased neuronal nitric oxide synthase dimerisation is involved in rat and human pancreatic beta cell hyperactivity in obesity.

AIMS/HYPOTHESIS: Pancreatic beta cell hyperactivity is known to occur in obesity, particularly in insulin-resistant states. Our aim was to investigate whether changes in neuronal nitric oxide synthase (nNOS) function affect beta cell compensation in two relevant models: the Zucker fa/fa rats and pancreatic islets from obese humans. METHODS: Glucose-induced insulin response was evaluated in the isolated perfused rat pancreas and in human pancreatic islets from obese individuals. Expression of nNOS (also known as NOS1) and subcellular localisation of nNOS were studied by quantitative RT-PCR, immunoblotting, immunofluorescence and electron microscopy. RESULTS: Pancreatic beta cells from Zucker fa/fa rats and obese individuals were found to be hyper-responsive to glucose. Pharmacological blockade of nNOS was unable to modify beta cell response to glucose in fa/fa rats and in islets from obese individuals, suggesting an abnormal control of insulin secretion by the enzyme. In both cases, nNOS activity in islet cell extracts remained unchanged, despite a drastic increase in nNOS protein and an enhancement in the dimer/monomer ratio, pointing to the presence of high amounts of catalytically inactive enzyme. This relative decrease in activity could be mainly related to increases in islet asymmetric dimethyl-arginine content, an endogenous inhibitor of nNOS activity. In addition, mitochondrial nNOS level was decreased, which contrasts with a strongly increased association with insulin granules. CONCLUSIONS/INTERPRETATION: Increased nNOS production and dimerisation, together with a relative decrease in catalytic activity and relocalisation, are involved in beta cell hyperactivity in insulin-resistant rats but also in human islets isolated from obese individuals.

Treatment with sodium tungstate delays diabetes onset and lowers hyperglycemia in the NOD mouse

Introduction: Sodium tungstate is an effective anti-diabetic agent in several animal models of diabetes mellitus in both short- and long-term treatments. Aims: To further characterize its therapeutic application, we studied whether this compound could act in autoimmune diabetes in the NOD (non-obese diabetic) mouse. Material and methods: Four-week-old female mice were given sodium tungstate for 24 weeks. Blood glucose was measured every 2 days throughout the entire experimental period. At the end of treatment, morphometric analysis of the pancreas was performed. Alternatively, diabetic mice were treated with tungstate and liver enzyme activity was determined. Results: We found that tungstate treatment delayed diabetes onset by 6 weeks. In addition, treated mice exhibited lower hyperglycemia at the onset of the disease and this parameter remained low until the end of treatment. Tungstate treatment had no effect on either the severity of insulitis or on β-cell mass. However, tungstate treatment induced a recovery of liver glucokinase and pyruvate kinase activities in diabetic animals. Conclusions: Administration of sodium tungstate to NOD mice corroborates its anti-diabetic properties, delaying diabetes onset and diminishing its incidence. The results indicate that, in the NOD mouse, as in other animal models, the liver is one of the main targets of tungstate actions (AU)

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Stable and functional regeneration of pancreatic beta-cell population in nSTZ-rats treated with tungstate.

AIMS/HYPOTHESIS: Sodium tungstate has recently emerged as an effective oral treatment for diabetes. We examined the effects of tungstate administration in the beta-cell mass of the pancreas as well as its therapeutic potential. METHODS: Sodium tungstate was administered via drinking water to healthy and neonatal streptozotocin (nSTZ)-diabetic rats for one month. The pancreas from each rat was removed and morphometric and immunocytochemical studies were carried out. The molecular mechanism of tungstate's action was also studied. RESULTS: In nSTZ rats administration of this compound normalised glycaemia, and increased insulinaemia and islet insulin content. Blood glucose concentrations were normalised as early as on day 4 of treatment, and tungstate treatment produced a partial recovery of beta-cell mass. The rats remained normoglycaemic after tungstate withdrawal. Morphometric studies showed that the increase in beta-cell mass was not due to beta-cell hypertrophy but to hyperplasia, with an increase in islet density in treated diabetic rats. Tungstate treatment increased extra-islet beta-cell replication without modifying intra-islet beta-cell replication rates. Moreover, the treatment induced increases in insulin-positive cells located close to ducts; and in PDX-1 positive cells scattered in the exocrine tissue, suggesting active neogenesis. In islets from treated diabetic rats, tungstate is able to increase the phosphorylation state of PDX-1 through the activation of p38. CONCLUSION/INTERPRETATION: These observations indicate that tungstate treatment is able to regenerate a stable, functional pancreatic beta-cell population which leads to and maintains normoglycaemia.

Effect of high glucose concentration on proinsulin biosynthesis and conversion by human islets.

In the present study we investigate whether glucose concentration could have an effect on proinsulin biosynthesis and processing. We cultured control human islets under chronic high and low glucose concentrations. After the culture period, islets were pulse-labeled and chased for different periods of time. Proteins from islets were collected, insulin immunoprecipitated, and analyzed by alkaline-urea gel electrophoresis. We have found an accelerated rate of proinsulin conversion by those islets exposed to high glucose concentration (at 24.4 mM of glucose), but not by those islets cultured at low glucose concentration (at 5.5 mM of glucose). However, we do not observe any decrease or increase on newly proinsulin synthesis in any of these conditions.