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Fluckey JD Cortright RN Tapscott E Koves T Smith L Pohnert S Dohm GL 《American journal of physiology. Endocrinology and metabolism》2004,286(5):E753-E758
A recent report from our group demonstrated that insulin facilitates muscle protein synthesis in obese Zucker rats. The purpose of this study was to determine whether PKC, a probable modulator of insulin signal transduction and/or mRNA translation, has a role in this insulin-mediated anabolic response. In the first portion of the study, gastrocnemius muscles of lean and obese Zucker rats (n = 5-7 for each phenotype) were bilaterally perfused with or without insulin to assess cytosolic and membrane PKC activity. Limbs perfused with insulin demonstrated greater PKC activity in both lean and obese Zucker rats (P < 0.05) compared with no insulin, but overall activity was greater in obese animals (by approximately 27% compared with lean, P < 0.05). To determine whether PKC plays a role in muscle protein synthesis, hindlimbs (n = 6-8 for each phenotype) were bilaterally perfused with or without insulin and/or GF-109203X (GF; a PKC inhibitor). The presence of GF did not influence the rates of insulin-mediated protein synthesis in gastrocnemius muscle of lean Zucker rats. However, when obese rats were perfused with GF (P < 0.05), the effect of insulin on elevating rates of protein synthesis was not observed. We also used phorbol 12-myristate 13-acetate (TPA, a PKC activator; n = 5-7 for each phenotype) with and without insulin to determine the effect of PKC activation on muscle protein synthesis. TPA alone did not elevate muscle protein synthesis in lean or obese rats. However, TPA plus insulin resulted in elevated rates of protein synthesis in both phenotypes that were similar to rates of insulin alone of obese rats. These results suggest that PKC is a modulator and is necessary, but not sufficient, for insulin-mediated protein anabolic responses in skeletal muscle. 相似文献
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Energy metabolism in uncoupling protein 3 gene knockout mice 总被引:27,自引:0,他引:27
Vidal-Puig AJ Grujic D Zhang CY Hagen T Boss O Ido Y Szczepanik A Wade J Mootha V Cortright R Muoio DM Lowell BB 《The Journal of biological chemistry》2000,275(21):16258-16266
Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCP3 has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined. 相似文献
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There is mounting evidence that the vanilloid (capsaicin) receptor; transient receptor potential channel, vanilloid subfamily member 1 (TRPV1), is subjected to multiple interacting levels of control. The first level is by reversible phosphorylation catalyzed by intrinsic kinases (e.g. protein kinase A and C) and phosphatases (e.g. calcineurin), which plays a pivotal role in receptor sensitization vs. tachyphylaxis. In addition, this mechanism links TRPV1 to intracellular signaling by various important endogenous as well as exogenous substances such as bradykinin, ethanol, nicotin and insulin. It is not clear, however, whether phosphorylation per se is sufficient to liberate TRPV1 under the inhibitory control of phosphatydylinositol-4,5-bisphosphate. The second level of control is by forming TRPV1 heteromers and their association with putative regulatory proteins. The next level of regulation is by subcellular compartmentalization. The membrane form of TRPV1 functions as a nonselective cation channel. On the endoplasmic reticulum, TRPV1 is present in two differentially regulated forms, one of which is inositol triphosphate-dependent whereas the other is not. These three TRPV1 compartments provide a versatile regulation of intracellular Ca(2+) levels. Last, there is a complex and poorly understood regulation of TRPV1 activity via control of gene expression. Factors that downregulate TRPV1 expression include vanilloid treatment and growth factor (notably, nerve growth factor) deprivation. By contrast, TRPV1 appears to be upregulated during inflammatory conditions. Interestingly, following experimental nerve injury and in animal models of diabetic neuropathy TRPV1 is present on neurons that do not normally express TRPV1. Combined, these findings imply an important role for aberrant TRPV1 expression in the development of neuropathic pain and hyperalgesia. In humans, disease-related changes in TRPV1 expression have already been described (e.g. inflammatory bowel disease and irritable bowel syndrome). The mechanisms that regulate TRPV1 gene expression under pathological conditions are unknown but a better understanding of these pathways has obvious implications for rational drug development. 相似文献
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Effect of aging on response to exercise training in humans: skeletal muscle GLUT-4 and insulin sensitivity. 总被引:3,自引:0,他引:3
The purpose of this study was to compare the effects of short-term exercise training on insulin-responsive glucose transporter (GLUT-4) concentration and insulin sensitivity in young and older individuals. Young and older women [22.4 +/- 0.8 (SE) yr, n = 9; and 60.9 +/- 1. 0 yr, n = 10] and men (20.9 +/- 0.9, n = 9; 56.5 +/- 1.9 yr, n = 8), respectively, were studied before and after 7 consecutive days of exercise training (1 h/day, approximately 75% maximal oxygen uptake). The older groups had more adipose tissue, increased central adiposity, and a lower maximal oxygen uptake. Despite these differences, increases in whole body insulin action (insulin sensitivity index, determined with an intravenous glucose tolerance test and minimal-model analysis) with training were similar regardless of age, in both the women and men (mean increase of 2.2 +/- 0.3-fold). This was accompanied by similar relative increases in muscle (vastus lateralis) GLUT-4 protein concentration, irrespective of age (mean increase of 3.1 +/- 0.7-fold). Body mass did not change with training in any of the groups. These data suggest that older human skeletal muscle retains the ability to rapidly increase muscle GLUT-4 and improve insulin action with endurance training. 相似文献
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Background
Molluscs are the most diverse marine phylum and this high diversity has resulted in considerable taxonomic problems. Because the number of species in Canadian oceans remains uncertain, there is a need to incorporate molecular methods into species identifications. A 648 base pair segment of the cytochrome c oxidase subunit I gene has proven useful for the identification and discovery of species in many animal lineages. While the utility of DNA barcoding in molluscs has been demonstrated in other studies, this is the first effort to construct a DNA barcode registry for marine molluscs across such a large geographic area.Methodology/Principal Findings
This study examines patterns of DNA barcode variation in 227 species of Canadian marine molluscs. Intraspecific sequence divergences ranged from 0–26.4% and a barcode gap existed for most taxa. Eleven cases of relatively deep (>2%) intraspecific divergence were detected, suggesting the possible presence of overlooked species. Structural variation was detected in COI with indels found in 37 species, mostly bivalves. Some indels were present in divergent lineages, primarily in the region of the first external loop, suggesting certain areas are hotspots for change. Lastly, mean GC content varied substantially among orders (24.5%–46.5%), and showed a significant positive correlation with nearest neighbour distances.Conclusions/Significance
DNA barcoding is an effective tool for the identification of Canadian marine molluscs and for revealing possible cases of overlooked species. Some species with deep intraspecific divergence showed a biogeographic partition between lineages on the Atlantic, Arctic and Pacific coasts, suggesting the role of Pleistocene glaciations in the subdivision of their populations. Indels were prevalent in the barcode region of the COI gene in bivalves and gastropods. This study highlights the efficacy of DNA barcoding for providing insights into sequence variation across a broad taxonomic group on a large geographic scale. 相似文献8.
Katie J Torley Juliano C da Silveira Peter Smith Russell V Anthony DN Rao Veeramachaneni Quinton A Winger Gerrit J Bouma 《Reproductive biology and endocrinology : RB&E》2011,9(1):2
Background
Gonadal differentiation in the mammalian fetus involves a complex dose-dependent genetic network. Initiation and progression of fetal ovarian and testicular pathways are accompanied by dynamic expression patterns of thousands of genes. We postulate these expression patterns are regulated by small non-coding RNAs called microRNAs (miRNAs). The aim of this study was to identify the expression of miRNAs in mammalian fetal gonads using sheep as a model. 相似文献9.
Molecular evolution of mitochondrial 12S RNA and cytochrome b sequences in the pantherine lineage of Felidae 总被引:4,自引:2,他引:2
DNA sequence comparisons of two mitochondrial DNA genes were used to infer
phylogenetic relationships among 17 Felidae species, notably 15 in the
previously described pantherine lineage. The polymerase chain reaction
(PCR) was used to generate sequences of 358 base pairs of the mitochondrial
12S RNA gene and 289 base pairs of the cytochrome b protein coding gene.
DNA sequences were compared within and between 17 felid and five nonfelid
carnivore species. Evolutionary trees were constructed using phenetic,
cladistic, and maximum likelihood algorithms. The combined results
suggested several phylogenetic relationships including (1) the recognition
of a recently evolved monophyletic genus Panthera consisting of Panthera
leo, P. pardus, P. onca, P. uncia, P. tigris, and Neofelis nebulosa; (2)
the recent common ancestry of Acinonyx jubatus, the African cheetah, and
Puma concolor, the American puma; and (3) two golden cat species, Profelis
temmincki and Profelis aurata, are not sister species, and the latter is
strongly associated with Caracal caracal. These data add to the growing
database of vertebrate mtDNA sequences and, given the relatively recent
divergence among the felids represented here (1-10 Myr), allow 12S and
cytochrome b sequence evolution to be addressed over a time scale different
from those addressed in most work on vertebrate mtDNA.
相似文献
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Xin Zhou Sarah J Adamowicz Luke M Jacobus R Edward DeWalt Paul DN Hebert 《Frontiers in zoology》2009,6(1):1-9