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news and views nebula and were subject to repeated episodes of shock heating for a million years or so. The Kauai workshop took place 20 years after another meeting in Hawaii on the origin of the Moon. That meeting is now recognized as the turning point in acceptance of the idea that the Moon formed following a giant impact of a Mars-sized body with Earth. The 2004 meeting may likewise take its place in history — as the time and place when it was explained how chondrules and CAIs were thermally processed by shock fronts in the solar nebula. ■ Alan P. Boss is in the Department of Terrestrial Magnetism, Carnegie Institution of Washington,
5241 Broad Branch Road NW, Washington DC 20015-1305, USA. e-mail:
[email protected] 1. Sorby, H. C. Nature 15, 495–498 (1877). 2. Hewins, R. H. in Chondrules and the Protoplanetary Disk (eds Hewins, R. H., Jones, R. H. & Scott, E. R. D.) 3–9 (Cambridge Univ. Press, 1996). 3. Desch, S. J. & Connolly, H. C. Jr Meteor. Planet. Sci. 37, 83–207 (2002). 4. Ciesla, F. J. & Hood, L. L. Icarus 158, 281–293 (2002). 5. Halliday, A. Nature 431, 253–254 (2004). 6. Bizarro, M., Baker, J. A. & Haack, H. Nature 431, 275–277 (2004). 7. Amelin, Y., Krot, A. N., Hutcheon, I. D. & Ulyanov, A. A. Science 297, 1678–1683 (2002). 8. Inaba, S., Wetherill, G. W. & Ikoma, M. Icarus 166, 46–62 (2003). 9. Wood, J. A. Meteor. Planet. Sci. 31, 641–645 (1996). 10. Boss, A. P. Astrophys. J. 616, 1265–1277 (2004).
Diabetes
Outfoxing insulin resistance? Marc Montminy and Seung-Hoi Koo Resistance to insulin predisposes people to diabetes; it is characterized by increased storage of fats and a failure to stop glucose synthesis. The molecular underpinnings of these effects have been uncovered. ype II diabetes affects some 5% of adults in most developed countries, and a far higher proportion of the population exhibits insulin resistance, a condition that predisposes individuals to diabetes. The mechanisms leading to insulin resistance are unclear, although the abnormal accumulation of certain fats in the liver (hepatic steatosis) is a contributing factor. On page 1027 of this issue, Stoffel and colleagues1 show that the inactivation of a protein called Foxa2 promotes steatosis and contributes to the development of diabetes in insulin-resistant animals. The results have implications for the design of new drugs to treat insulin resistance and diabetes. Energy balance in mammals resembles today’s hybrid cars — we use a variable mix of glucose and fat as energy substrates, depending on food intake. During waking and feeding hours, we use glucose as an efficient source of energy, and under fasting conditions, during sleep for example, we burn primarily fat. Fat stores, called triglycerides, are converted to circulating fatty acids, and are further broken down in a process known as fatty-acid oxidation. In the fasting state, the liver also maintains normal circulating levels of glucose (which is essential for brain function) by synthesizing glucose anew, in a process known as gluconeogenesis. The capacity of the liver to synthesize glucose and burn fat is governed by a set of ignition switches, called transcription factors, that operate in the nucleus to turn genes on and off 2. These switches respond to changes in circulating hormones — principally insulin and glucagon — that allow the liver cell to change gears between feeding and
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fasting metabolism. In response to feeding, insulin triggers the activation of a cascade of proteins inside the cell, each transmitting the feeding signal to the next through a chemical modification known as phosphorylation. In insulin-resistant states, the orderly phosphorylation of certain proteins in response to insulin is damaged, preventing insulin from correctly regulating glucose and fat metabolism3. As a consequence, insulinresistant individuals exhibit hyperglycaemia (high blood glucose), partly because of elevated gluconeogenesis in the liver. Despite this inability to inhibit glucose production in diabetes, insulin still seems to be capable of shutting off the switch that normally promotes fat burning (fatty-acid oxidation) during fasting. This phenomenon, known as mixed insulin resistance, implies that the insulin signal is transmitted preferentially to the fatty-acid-oxidation switch rather than the glucose switch, the unfortunate consequence being that insulinresistant individuals are not only hyperglycaemic but also accumulate triglycerides in the liver rather than breaking them down. In their work, Stoffel and colleagues1 test the notion that distinct switches control glucose and fat metabolism in the liver, and that one of these switches might be far more sensitive to insulin than the other.They show that the protein Foxa2, a member of the ‘forkhead’ family of transcription factors, is a key switch that regulates fatty-acid breakdown in the liver during fasting. Foxa2 resembles another forkhead-family member called Foxo1, which is well known to promote gluconeogenesis in liver in the fasted state3. Feeding inactivates both Foxo1 and Foxa2 switches through phosphorylation —
but the surprise, and the central point, of this paper1 is that Foxa2 is far more sensitive to insulin signals than is Foxo1, and consequently Foxa2 is turned off even in insulinresistant states, whereas Foxo1 is not. Why is Foxa2 so much more sensitive to insulin? The answer is still murky, but the authors point to one possible explanation. Under feeding conditions, insulin stimulates two separate relay systems in liver cells that are distinguished by two key components: the insulin-receptor substrates IRS1 and IRS2 (ref. 4; Fig. 1). Stoffel and colleagues found that the Foxo1 switch is turned off only by the IRS2 relay system, but Foxa2 can be turned off by both IRS1 and IRS2. Thus, by virtue of its sensitivity to both IRS1 and IRS2 signals, Foxa2 may be turned off by insulin more readily than Foxo1. Levels of circulating insulin are chronically elevated in insulin resistance, in part because of the abnormal gluconeogenesis in the liver, leading the authors to suggest that this hyperinsulinaemia causes Foxa2 to remain inactive, even during fasting periods. As a consequence of this block in fatty-acid oxidation, the liver begins to accumulate triglycerides. To test this model, Stoffel and colleagues used an altered Foxa2 with a mutation (denoted T156A) that blocks the phosphorylation of Foxa2 in response to insulin. Remarkably, when the mutant Foxa2 was
Figure 1 Model for insulin signalling in the liver. After a meal, insulin binds to its receptor in liver, activating two major pathways (one involving insulin-receptor substrate-1, IRS1, the other involving IRS2). Akt is a key enzyme in both signalling relays. The pathways shut down the synthesis of glucose (gluconeogenesis) and the burning of stored fats (fatty-acid oxidation) by phosphorylating Foxo1 and Foxa2. Stoffel and colleagues1 now show that Foxo1 is phosphorylated only through the IRS2 pathway, whereas Foxa2 is phosphorylated in response to both IRS1 and IRS2, accounting for its enhanced sensitivity to insulin signals.
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news and views introduced into the livers of diabetic mice, it not only reversed hepatic steatosis but also improved insulin sensitivity. The results potentially explain how insulin can have different effects on glucose and fat metabolism, and provide clues to how hepatic steatosis develops and leads to diabetes. Although this study brings up numerous questions, perhaps the most intriguing of these concerns the mechanism by which insulin shuts down Foxa2 preferentially over Foxo1. Presumably this difference reflects the involvement of certain components in the IRS1 and IRS2 pathways that associate with and favour Foxa2 phosphorylation. Identifying these components will be impor-
tant in understanding the basis of insulin selectivity. Regardless, the ability of the mutant Foxa2 to reverse hepatic steatosis provides a glimpse into potential new therapies for hepatic steatosis, and might one day provide clinicians with new measures to prevent the progression from insulin resistance to diabetes. ■ Marc Montminy and Seung-Hoi Koo are at The Salk Institute for Biological Studies, La Jolla, California 92130, USA. e-mail:
[email protected] 1. Wolfrum, C., Asilmaz, E., Luca, E., Friedman, J. M. & Stoffel, M. Nature 432, 1027–1032 (2004). 2. Spiegelman, B. M. & Heinrich, R. Cell 119, 157–167 (2004). 3. Saltiel, A. & Kahn, C. R. Nature 414, 799–806 (2001). 4. White, M. Mol. Cell. Biochem. 182, 3–11 (1998).
Applied physics
Nanotube antennas M. S. Dresselhaus An antenna array that is metres high and wide can detect and transmit radio waves. This effect has now been demonstrated at much smaller electromagnetic wavelengths in a nanoscale array of carbon nanotubes. n Applied Physics Letters, Wang et al.1 show in a clear way that an array of aligned carbon nanotubes can behave as an electromagnetic antenna. Their practical demonstration not only confirms a predicted effect but also points to its use in practical devices. Antennas are familiar as detectors and transmitters of radio waves. But, depending on their dimensions, antennas can receive different wavelengths — radio, optical, microwave, and so on. All antennas have two major properties. First, their response varies with the polarization of the incoming radiation (polarization means that the electric field of the radiation has a particular orientation). Transmission is weakest if the plane of polarization is at 90° to the antenna’s long axis: the polarization effect. And second, their response varies with their length, being strongest when the length is a multiple of half of the wavelength () of the radiation (0.5, 1.0, 1.5, and so on): the antennalength effect. The likely polarization and antenna properties of carbon nanotubes were recognized from a theoretical standpoint2 soon after the first experimental synthesis3,4 of single-wall carbon nanotubes in 1993. Conceptually, single-wall carbon nanotubes (SWCNTs) can be considered to be formed by the rolling of a single layer of graphite (called a graphene layer) into a seamless cylinder. A multiwall carbon nanotube (MWCNT) can similarly be considered to be a coaxial assembly of cylinders of SWCNTs, like a Russian doll, one within another; the separation between tubes is about equal to that between the layers in natural graphite.
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Hence, nanotubes are one-dimensional objects with a well-defined direction along the nanotube axis that is analogous to the in-plane directions of graphite. Wang et al.1 performed their experiments on random arrays of MWCNTs, aligned along their long axes and looking, at the nanoscale,like a dense forest of trees growing up from a silicon substrate. Each MWCNT in their nanotube array behaves effectively as a metallic rod about 50 nm in diameter and 200–1,000 nm in length (although within each array the MWCNTs are about the same length). The particular novelty of this work is the clear and direct demonstration of the antenna-length effect. Using visible light, Wang et al. show that maxima occur in the amount of reflected light when the average length of the nanotubes in an array is a halfintegral multiple of the wavelength of the incident light. They also provide a vivid demonstration of the polarization effect by comparing how much polarized light is reflected from a nanotube array and how much from a highly reflective metal surface positioned alongside the nanotube forest. For the metal surface, the electric-field vector must be in the plane of the metal surface for the light to be maximally reflected. In contrast, reflection from the nanotube arrays is strongest when the electric-field vector of the polarized light falls along the axis of the nanotubes (normal to the substrate). These properties of nanotube arrays are related to the special electromagnetic behaviour of layered graphite, which has a strongly anisotropic ‘skin depth’. The skin depth is the characteristic distance of penetration of
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an electromagnetic wave into a material.If the incident radiation is polarized parallel to the plane of the graphite layers, the skin depth is short and the light is strongly absorbed. But if the polarization is normal to the plane of the layers, the penetration depth of the light is more than ten times larger and the absorption is very much weaker. This anisotropy in the electromagnetic properties of graphite was commonly exploited in the construction of infrared and microwave polarizers,before the development of Polaroid film in the 1960s. Such polarization effects are useful in fundamental studies of the optical absorption, reflection and emission of carbon nanotubes. The intensity of the scattered light is proportional to the light’s absorption and emission5–7 and is thus a sensitive probe of optical processes in carbon nanotubes. Furthermore, polarization has a major role in determining the right-handedness or lefthandedness of a carbon nanotube8. As Wang et al.1 note, polarization effects in carbon nanotubes have been observed by several groups, in experiments on bundles of MWCNTs9 and of SWCNTs10, individual metallic SWCNTs11 and individual semiconducting12 SWCNTs, and on very-smalldiameter (0.4 nm) SWCNTs in a zeolite template13. By performing polarization studies on an individual SWCNT, total suppression of the electric field normal to the nanotube axis could be demonstrated, and the dipole pattern of an individual nanotube could be studied — both when the tube was well isolated from other SWCNTs and when it interacted with a nearby SWCNT12. The work by Wang et al.1 suggests a host of applications in optoelectronics, for example infrared polarizers or polarization detectors, using arrays in which the MWCNTs have a range of lengths, and wavelength-specific detectors, for which the MWCNTs are fabricated to all have the same desired length. MWCNTs are preferable to SWCNTs for their electrical metallicity and greater mechanical robustness, and their random spacing in the arrays suppresses interference effects. The preparation of the MWCNT arrays could easily be extended to a high-throughput process with the use of established technology. Over the decade-long history of carbon nanotubes there has been substantial investment by the private sector in nanotube research and development: the technology devised by Wang et al.1 may well spawn optoelectronic applications of considerable commercial significance. ■ M. S. Dresselhaus is in the Department of Physics and the Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. e-mail:
[email protected] 1. Wang, Y. et al. Appl. Phys. Lett. 85, 2607–2609 (2004). 2. Ajiki, H. & Ando, T. Physica B Cond. Matt. 201, 349–352 (1994). 3. Iijima, S. & Ichihashi, T. Nature 363, 603–605 (1993). 4. Bethune, D. S. et al. Nature 363, 605–607 (1993).
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