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OBJECTIVE-Diabetes is caused by a deficiency of pancreatic ␤-cells that produce insulin. Approaches to enhance ␤-cell mass by increasing proliferation and survival are desirable. We determined whether stromal cell-derived factor (SDF)-1/CXCL12 and its receptor, CX chemokine receptor (CXCR)4, are important for the survival of ␤-cells. RESEARCH DESIGN AND METHODS-Mouse pancreata andclonal ␤-cells were examined for expression of SDF-1 and CXCR4, activation of AKT and downstream signaling pathways by SDF-1, and protection against apoptosis and diabetes induced by streptozotocin (STZ). RESULTS-CXCR4is expressed in ␤-cells, and SDF-1 is expressed in microvascular endothelial cells within the islets and in surrounding interstitial stromal tissue. Transgenic mice overexpressing SDF-1 within their ␤-cells (RIP-SDF-1 mice) are resistant to STZ-induced ␤-cell apoptosis and diabetes. In MIN6 ␤-cells, a CXCR4 antagonist (AMD3100) induces apoptosis, increases reactive oxygen species, decreases expression levels of the anti-apoptotic protein Bcl-2, and reduces phosphorylation of the proapoptotic protein Bad. Active phosphorylated prosurvival kinase Akt is increased both in the ␤-cells of RIP-SDF-1 mice and in INS-1 cells treated with SDF-1 and sensitive to AMD3100. Inhibition of AKT expression by small interfering RNA attenuates the ameliorative effects of SDF-1 on caspase-dependent apoptosis induced by thapsigargin or glucose deprivation in INS-1 ␤-cells. Specific inhibition of Akt activation by a soluble inhibitor (SH-5) reverses the anti-apoptotic effects of SDF-1 in INS-1 cells and mouse islets.CONCLUSIONS-SDF-1 promotes pancreatic ␤-cell survival via activation of Akt, suggesting that SDF-1 agonists may prove beneficial for treatment of diabetes.

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Tip-enhanced Raman scattering microscopy is a powerful technique for analysing nanomaterials at high spatial resolution far beyond the diffraction limit of light. However, imaging of intrinsic properties of materials such as individual molecules or local structures has not yet been achieved even with a tip-enhanced Raman scattering microscope. Here we demonstrate colour-coded tip-enhanced Raman scattering imaging of strain distribution along the length of a carbon nanotube. The strain is induced by dragging the nanotube with an atomic force microscope tip. A silver-coated nanotip is employed to enhance and detect Raman scattering from specific locations of the nanotube directly under the tip apex, representing deformation of its molecular alignment because of the existence of local strain. Our technique remarkably provides an insight into localized variations of structural properties in nanomaterials, which could prove useful for a variety of applications of carbon nanotubes and other nanomaterials as functional devices and materials.

We present a near-field Raman investigation in the subnanometric vicinity of a metallic nanotip, where the tip-sample distance is precisely controlled by our newly developed time-gated illumination technique. Using this scheme on an isolated carbon nanotube, we have profiled the spatial decay of evanescent light. We also investigated extremely short-ranged chemical and mechanical interactions between the metal on the tip apex and the molecules of an adenine sample, which are observable only within the subnanometric vicinity of the tip. The results show a near-field Raman investigation with an accuracy of better than a few angstroms. Further, this shows strong promise for superhigh resolution in optical microscopy based on this technique.

Aims/hypothesis The endogenous production of stromal cell-derived factor-1 (SDF-1) in beta cells in transgenic mice attenuates the development of diabetes in response to streptozotocin. Here we propose that beta cell injury induces SDF-1 production, and the SDF-1/chemokine (C-X-C motif) receptor 4 (CXCR4) interaction auto-activates Sdf1 expression, resulting in the autocrine production of SDF-1 by beta cells and the paracrine activation of glucagon-like peptide-1 (GLP-1) production by alpha cells. Methods SDF-1 production in adult mouse and human islets and rat INS-1 cells was measured in models of beta cell injury. The paracrine actions of SDF-1 on GLP-1 production in alpha cells were explored. The potential synergism between the growth-promoting actions of GLP-1 and the pro-survival actions of SDF-1 on the preservation of cell mass was evaluated by cell viability assays. Results In adult islets and INS-1 cells, Sdf1 expression was re-induced in response to injury. The interaction of SDF-1 with its receptor on alphaTC1 cells activated protein kinase Akt, stimulated cell proliferation and induced the expression of prohormone convertase 1/3 and the consequent production of GLP-1 in alpha cells. The combination of GLP-1 and SDF-1 additively enhanced both the growth and longevity of INS-1 beta cells. Conclusions/interpretation The results of these studies suggest that in response to beta cell injury and the ensuing induction of SDF-1, the biological function of alpha cells switches from the production of glucagon to the provision of the local growth factor GLP-1 which, in combination with SDF-1, promotes the growth, survival and viability of the beta cells.

We report on the experimental identification of Raman modes that are enhanced through the chemical effect in surface enhanced Raman spectroscopy of 4-aminothiophenol (also known as p-mercaptoaniline) adsorbed on gold substrate. Introduction of a thin spacer layer between the metal and the sample can prevent any possible chemical bonding between metal atoms and sample molecules, hence such a sample shows only those Raman modes that are enhanced through the electromagnetic effect. Alternatively, a significant increase in the chemical effect could be observed in the presence of halide ions as compared to their absence. This result provides another way to experimentally identify those Raman modes that undergo chemical enhancement. In addition, apart from the electromagnetic-based resonance in SERS, chemical enhancement also shows a resonance with varying wavelength of the excitation light, which provides yet another way to experimentally identify chemically enhanced Raman modes in SERS. Some new chemically enhanced modes could be observed when the sample molecules were sandwiched between gold substrate and a gold nanotip. † Part of the "Martin Moskovits Festschrift".