Apolipoprotein CIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src

Apolipoprotein CIII (ApoCIII) not only serves as an inhibitor of triglyceride hydrolysis but also participates in diabetes-related pathological events such as hyperactivation of voltage-gated Ca²⁺ (Ca_V) channels in the pancreatic β cell. However, nothing is known about the molecular mechanisms whereby ApoCIII hyperactivates β cell Ca_V channels. We now demonstrate that ApoCIII increased Ca_V1 channel open probability and density. ApoCIII enhanced whole-cell Ca²⁺ currents and the Ca_V1 channel blocker nimodipine completely abrogated this enhancement. The effect of ApoCIII was not influenced by individual inhibition of PKA, PKC, or Src. However, combined inhibition of PKA, PKC, and Src counteracted the effect of ApoCIII, similar results obtained by coinhibition of PKA and Src. Moreover, knockdown of β1 integrin or scavenger receptor class B type I (SR-BI) prevented ApoCIII from hyperactivating β cell Ca_V channels. These data reveal that ApoCIII hyperactivates β cell Ca_V1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src.     

Ptolemy's maps of earth and the heavens: A new interpretation

Communicated by A. Aaboe     

Inositol trisphosphate-dependent periodic activation of a Ca(2+)-activated K+ conductance in glucose-stimulated pancreatic beta-cells.

Glucose-stimulated insulin secretion is associated with the appearance of electrical activity in the pancreatic beta-cell. At intermediate glucose concentrations, beta-cell electrical activity follows a characteristic pattern of slow oscillations in membrane potential on which bursts of action potentials are superimposed. The electrophysiological background of the bursting pattern remains unestablished. Activation of Ca(2+)-activated large-conductance K+ channels (KCa channel) has been implicated in this process but seems unlikely in view of recent evidence demonstrating that the beta-cell electrical activity is unaffected by the specific KCa channel blocker charybdotoxin. Another hypothesis postulates that the bursting arises as a consequence of two components of Ca(2+)-current inactivation. Here we show that activation of a novel Ca(2+)-dependent K+ current in glucose-stimulated beta-cells produces a transient membrane repolarization. This interrupts action potential firing so that action potentials appear in bursts. Spontaneous activity of this current was seen only rarely but could be induced by addition of compounds functionally related to hormones and neurotransmitters present in the intact pancreatic islet. K+ currents of the same type could be evoked by intracellular application of GTP, the effect of which was mediated by mobilization of Ca2+ from inositol 1,4,5-trisphosphate (InsP3)-sensitive intracellular Ca2+ stores. These observations suggest that oscillatory glucose-stimulated electrical activity, which is correlated with pulsatile release of insulin, results from the interaction between the beta-cell and intraislet hormones and neurotransmitters. Our data also provide evidence for a close interplay between ion channels in the plasma membrane and InsP3-induced mobilization of intracellular Ca2+ in an excitable cell.     

An electrochemical and microstructural characterization of steel-mortar admixed with corrosion inhibitors

The present research brings new insights on the role of admixed corrosion inhibitors in the processes of cement hydration and rebar corrosion.The admixing of NaCl and the corrosion inhibitors in fresh mortar was found to alter the morphology and microstructure of the hardened mortar at the steel-mortar interfacial region.The admixing of the inhibitors increased the risk of carbonation of cement hydrates at the steel-mortar interfacial region,but partially displaced chloride ions. Chloride and the admixed in...     

The imidazoline RX871024 induces death of proliferating insulin-secreting cells by activation of c-jun N-terminal kinase

An insufficient number of insulin-producing β-cells is a major cause of defective control of blood glucose in both type 1 and type 2 diabetes. The aim of this study was to clarify whether the insulinotropic imidazolines can affect the survival of highly proliferating insulin-secreting cells, here exemplified by the MIN6 cell line. Our data demonstrate that RX871024, but not efaroxan, triggered MIN6 cell death and potentiated death induced by a combination of the pro-inflammatory cytokines interleukin-1β, interferon- γ and tumor necrosis factor-α. These effects did not involve changes in nitric oxide production but correlated with stimulation of c-jun N-terminal kinase (JNK) activity and activation of caspases-1, -3, -8 and -9. Our results suggest that the imidazoline RX871024 causes death of highly proliferating insulin-secreting cells, putatively via augmentation of JNK activity, a finding that may impact on the possibility of using compounds of similar activity in the treatment of diabetes. Received 13 December 2007; received after revision 5 February 2008; accepted 6 February 2008     

纳米技术与发展中国家

作者将“nano*”与世界银行确定的每个经济类主题词组合检索，结果发现发展中国家普遍在从事
纳米技术研发。进一步研究表明，尽管发展中国家纳米技术的研发能力随着合作和信息利用的加强而提高，
但是这些国家已经偏离了纳米技术的“社会开发”这一通常被认为是最适于发展中国家的研究宗旨。另外，
对卫生保健相关专利的分析证实，各国实力严重不平衡，存在所谓的“纳米鸿沟”现象。在发展中国家中，
中国拥有的专利权所占份额很高，因此“纳米鸿沟”不仅存在于发展中国家和发达国家之间，在发展中国
家也同样存在。发展中国家的研发水平较低，纳米技术有可能走向以往导致全球技术大分裂的技术老路。     

Evidence for the presence of virus in clonal insulin-producing RINm5F cells

Summary The ultrastructural morphology of the clonal insulin-producing cell line, RINm5F, was investigated. Virus-like particles, probably C type viruses, were identified both intra- and extracellularly. Because these particles could not be found in the original transplantable tumor, it is probable that viruses were induced at some later stage in the development of the RINm5F cell line. All investigators using the RINm5F cells should be aware of the fact that these cells may contain one or several types of viruses, and of the possibility that these particles may interfere with a variety of cellular functions.This work was supported by grants from the Lake County Medical Center Developmental Agency (to VH and PWB) and the American Heart Association, Indiana Affiliate (to PWB,^*USA) and by the Swedish Medical Research Council (12X-562), the Swedish Diabetes Association, the Nordic Insulin Foundation and Åke Wibergs Foundation (^**Sweden). Per-Olof Berggren is a recipient of a postdoctoral fellowship from the Swedish Medical Research Council.     

Amplitude spectroscopy of a solid-state artificial atom

The energy-level structure of a quantum system, which has a fundamental role in its behaviour, can be observed as discrete lines and features in absorption and emission spectra. Conventionally, spectra are measured using frequency spectroscopy, whereby the frequency of a harmonic electromagnetic driving field is tuned into resonance with a particular separation between energy levels. Although this technique has been successfully employed in a variety of physical systems, including natural and artificial atoms and molecules, its application is not universally straightforward and becomes extremely challenging for frequencies in the range of tens to hundreds of gigahertz. Here we introduce a complementary approach, amplitude spectroscopy, whereby a harmonic driving field sweeps an artificial atom through the avoided crossings between energy levels at a fixed frequency. Spectroscopic information is obtained from the amplitude dependence of the system's response, thereby overcoming many of the limitations of a broadband-frequency-based approach. The resulting 'spectroscopy diamonds', the regions in parameter space where transitions between specific pairs of levels can occur, exhibit interference patterns and population inversion that serve to distinguish the atom's spectrum. Amplitude spectroscopy provides a means of manipulating and characterizing systems over an extremely broad bandwidth, using only a single driving frequency that may be orders of magnitude smaller than the energy scales being probed.