Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet β-cells

We studied interactive effects of insulinotropic GLP-1 and insulinostatic ghrelin on rat pancreatic islets. GLP-1 potentiated glucose-induced insulin release and cAMP production in isolated islets and [Ca(2+)](i) increases in single β-cells, and these potentiations were attenuated by ghrelin. Ghrelin suppressed [Ca(2+)](i) responses to an adenylate cyclase activator forskolin. Moreover, GLP-1-induced insulin release and cAMP production were markedly enhanced by [D-lys(3)]-GHRP-6, a ghrelin receptor antagonist, in isolated islets. These results indicate that both exogenous and endogenous islet-derived ghrelin counteracts glucose-dependent GLP-1 action to increase cAMP production, [Ca(2+)](i) and insulin release in islet β-cells, positioning ghrelin as a modulator of insulinotropic GLP-1.     

Production of TMC-151, TMC-154 and TMC-171, a new class of antibiotics, is specific to ‘Gliocladium roseum’ group

A novel class of fungal metabolites, TMC-151, TMC-154, and TMC-171 series compounds, was found exclusively inGliocladium catenulatum, Clonostachys rosea and closely related strains. These compounds were not detected in any other fungi examined. The production spectrum of each component was correlated to the morphology of the secondary conidiophores and the conidia. TMC-151 was limited toClonostachys rosea (formerlyG. roseum) forming navicular or reniform conidia orG. catenulatum with gray-green conidial masses, whereas TMC-154 and 171 were limited to the strains closely related toGliocladium roseum, which grew more slowly and formed more symmetrical conidia.     

2'-O,4'-C-ethylene-bridged nucleic acids (ENA): highly nuclease-resistant and thermodynamically stable oligonucleotides for antisense drug.

To develop antisense oligonucleotides, novel nucleosides, 2'-O,4'-C-ethylene nucleosides and their corresponding phosphoramidites, were synthesized as building blocks. The 1H NMR analysis showed that the 2'-O,4'-C-ethylene linkage of these nucleosides restricts the sugar puckering to the N-conformation as well as the linkage of 2'-O,4'-C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA). The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand (DeltaT(m)=+5.2 degrees C/modification) and were more nuclease-resistant than natural DNA and BNA/LNA. These results indicate that ENA have better properties as antisense oligonucleotides than BNA/LNA.     

Synthesis of Dihydrohelminthosporic and Allodihydrohelminthosporic Acids and their Plant Growth-regulating Activity

Li-NH₃ reduction of helminthosporic acid gave dihydrohelminthosporic acid (III) and allodihydrohelminthosporic acid (IV). III and IV are the epimers with respect to the carboxyl and III is labil form. The stereochemistry of III and IV is elucidated from the chemical and spectroscopic evidences. III showed a marked plant growth promoting activity but IV did not.     

EGF-Induced sustained tyrosine phosphorylation and decreased rate of down-regulation of EGF receptor in PC12h-R cells which show neuronal differentiation in response to EGF

PC12h-R cell, a subclone of PC12 cells, exhibited a neuron-like phenotype, including neurite outgrowth and increased acetylcholinesterase activity, in response to epidermal growth factor (EGF) as well as nerve growth factor (NGF). We examined the mechanism by which EGF induced the neuronal differentiation in PC12h-R cells. The EGF-induced neuronal differentiation of PC12h-R cells was not blocked by K252a, whereas that induced by NGF was. EGF induced sustained tyrosine phosphorylation of the EGF receptor in PC12h-R cells, but not in the parent PC12h cells, which do not show neuronal differentiation in response to EGF. In addition, the rate of EGF-induced down-regulation of the EGF receptor in PC12h-R cells was decreased compared with that in PC12h cells. Furthermore, we found that the duration of EGF-induced tyrosine phosphorylation of the EGF receptor in PC12h-R cells was similar to that of NGF-induced tyrosine phosphorylation of p140 ^trkA in PC12h cells. The EGF-induced phosphorylation of the EGF receptor in PC12h cells was less sustained than that of p140 ^trkA by NGF in PC12h cells. These findings suggested that the EGF-induced neuronal differentiation of PC12h-R cells is due to the sustained activation of the EGF receptor, resulting from the decreased down-regulation of the EGF receptor and that the duration of the receptor tyrosine kinase activity determines the cellular responses of PC12 cells. We concluded that sustained activation of the receptor tyrosine kinase induces neuronal differentiation, although transient activation promotes proliferation of PC12 cells. Special issue dedicated to Dr. Hans Thoenen.     

Microscopical Investigation of the Efifect of Helminthosporol on Rice Seedlings

The elongation of the second leaf sheaths of rice seedlings was promoted strongly by helminthosporol as well as by gibberellic acid. A greater dosage of helminthosporol was required in order to induce the same amount of elongation. Cells of treated plants were somewhat longer than those of controls. The elongation of the second leaf sheath was caused mainly by an increase in cell number. Both helminthosporol and gibberellic acid promoted the elongation of cells in the basal portion of the second leaf sheath.     

Application of Nitrate Reductase for the Determination of Nitrate in Meat and Fishery Products

A rapid and specific method is described for the determination of nitrate in meat and fishery products.

Nitrate separated from foods by extraction with 1/50Ν sodium hydroxide and ultrafiltration was readily reduced to nitrite by the use of respiratory nitrate reductase (NR) from Escherichia coli K-12. The nitrite so obtained can be determined by the specific diazotation-coupling reaction method.

The use of an enzymatic reaction resulted in quantitative reduction of nitrate, and the method was relatively free of interferences. Recoveries of 10 and 100 ppm of nitrate from 5 samples of meat and fishery products ranged from 92.8 to 97.8% for 10 ppm and 97.8 to 99.4% for 100 ppm with a detection limit of 0.5 ppm.     

Structures of Ezomycins A1 and A2

The structures of ezomycins A₁. and A₂, antifungal antibiotics produced by a strain of Streptomyces, were determined as 1 and 2, respectively, by degradative and spectrometric studies.     

Isolation,Structure and Physiological Activities of Piericidin B,Natural Insecticide Produced by a Streptomyces

Piericidin B was isolated from mycellia of Streptomyces mobaraensis besides piericidin A. On the basis of IR, NMR and mass spectral studies together with chemical evidences, its structure was assigned as Id. Its physiological activities are also deescribd.