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Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40 总被引:32,自引:0,他引:32
Itoh Y Kawamata Y Harada M Kobayashi M Fujii R Fukusumi S Ogi K Hosoya M Tanaka Y Uejima H Tanaka H Maruyama M Satoh R Okubo S Kizawa H Komatsu H Matsumura F Noguchi Y Shinohara T Hinuma S Fujisawa Y Fujino M 《Nature》2003,422(6928):173-176
Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue. Insulin is secreted from pancreatic beta cells in response to elevated plasma glucose, with various factors modifying its secretion. Free fatty acids (FFAs) provide an important energy source as nutrients, and they also act as signalling molecules in various cellular processes, including insulin secretion. Although FFAs are thought to promote insulin secretion in an acute phase, this mechanism is not clearly understood. Here we show that a G-protein-coupled receptor, GPR40, which is abundantly expressed in the pancreas, functions as a receptor for long-chain FFAs. Furthermore, we show that long-chain FFAs amplify glucose-stimulated insulin secretion from pancreatic beta cells by activating GPR40. Our results indicate that GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs. 相似文献
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Summary The effects of tetraethylammonium (TEA) on the action potential in cultured chick embryonic heart muscle cells were investigated. The onset of prolongation of the action potential occurred within 10 min following intracellular iontophoretic application of TEA, but after more than 50 min following extracellular application. These facts suggest that the major site of action of TEA is on the inner surface of the membrane in these cells. 相似文献
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Host-dependent evolution of three papova viruses 总被引:13,自引:0,他引:13
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Evidence from fluid inclusions for microbial methanogenesis in the early Archaean era 总被引:5,自引:0,他引:5
Methanogenic microbes may be one of the most primitive organisms, although it is uncertain when methanogens first appeared on Earth. During the Archaean era (before 2.5 Gyr ago), methanogens may have been important in regulating climate, because they could have provided sufficient amounts of the greenhouse gas methane to mitigate a severely frozen condition that could have resulted from lower solar luminosity during these times. Nevertheless, no direct geological evidence has hitherto been available in support of the existence of methanogens in the Archaean period, although circumstantial evidence is available in the form of approximately 2.8-Gyr-old carbon-isotope-depleted kerogen. Here we report crushing extraction and carbon isotope analysis of methane-bearing fluid inclusions in approximately 3.5-Gyr-old hydrothermal precipitates from Pilbara craton, Australia. Our results indicate that the extracted fluids contain microbial methane with carbon isotopic compositions of less than -56 per thousand included within original precipitates. This provides the oldest evidence of methanogen (> 3.46 Gyr ago), pre-dating previous geochemical evidence by about 700 million years. 相似文献
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Immunological memory in the antibody system is generated in T-cell-dependent responses and carried by long-lived memory B cells that recognize antigen by high-affinity antibodies. But it remains controversial whether these B cells represent true 'memory' cells (that is, their maintenance is independent of the immunizing antigen), or whether they are a product of a chronic immune response driven by the immunizing antigen, which can be retained in the organism for extended time periods on the surface of specialized antigen-presenting cells (follicular dendritic cells). Cell transfer experiments provided evidence in favour of a role of the immunizing antigen; however, analysis of memory cells in intact animals, which showed that these cells are mostly resting and can persist in the absence of detectable T-cell help or follicular dendritic cells, argued against it. Here we show, by using a genetic switch mediated by Cre recombinase, that memory B cells switching their antibody specificity away from the immunizing antigen are indeed maintained in the animal over long periods of time, similar to cells retaining their original antigen-binding specificity. 相似文献
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Reactive oxygen species (ROS) have been identified as central mediators in certain signalling events. In the heart, ROS have important functions in ischaemia/reperfusion-induced cardiac injury and in cytokine-stimulated hypertrophy. Extracellular signal-regulated kinase (ERK) is one of the ROS-responsive serine/threonine kinases. Previous studies showed that tyrosine kinases and small G proteins are involved in the activation of ERK by ROS; however, the initial target protein of ROS that leads to ERK activation remains unknown. Here we show that inhibition of the betagamma-subunit of G protein (G betagamma) attenuates hydrogen peroxide (H2O2)-induced ERK activation in rat neonatal cardiomyocytes. The G betagamma-responsive ERK activation induced by H2O2 is independent of ligands binding to Gi-coupled receptors, but requires phosphatidylinositol-3-kinase and Src activation. In in vitro studies, however, treatment with H2O2 increases [35S]GTP-gammaS binding to cardiac membranes and directly activates purified heterotrimeric Gi and Go but not Gs. Analysis using heterotrimeric Go and its individual subunits indicates that H2O2 modifies G alpha(o) but not G betagamma, which leads to subunit dissociation. We conclude that G alpha(i) and G alpha(o) are critical targets of oxidative stress for activation of ERK. 相似文献
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Geographical unifromity of selectively neutral polymorphisms 总被引:3,自引:0,他引:3
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