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| 1 | Knockout mouse models of insulin signaling: Relevance past and future显示文摘Insulin resistance is a hallmark of type 2 diabetes. In an effort to understand and treat this condition, re searchers have used genetic manipulation of mice to uncover insulin signaling pathways and determine the effects of their perturbation. After decades of research much has been learned, but the pathophysiology o insulin resistance in human diabetes remains contro versial, and treating insulin resistance remains a chal lenge. This review will discuss limitations of mouse models lacking select insulin signaling molecule genes In the most influential mouse models, glucose metabo lism differs from that of humans at the cellular, organ and whole-organism levels, and these differences limi the relevance and benefit of the mouse models both in terms of mechanistic investigations and therapeutic development. These differences are due partly to im mutable differences in mouse and human biology, and partly to the failure of genetic modifications to produce an accurate model of human diabetes. Several fac tors often limit the mechanistic insights gained from experimental mice to the particular species and strain including: developmental effects, unexpected meta bolic adjustments, genetic background effects, and technical issues. We conclude that the limitations and weaknesses of genetically modified mouse models of insulin resistance underscore the need for redirection of research efforts toward methods that are more directly relevant to human physiology. | Anne E Bunner P Charukeshi Chandrasekera Neal D Barnard | 2014 | World Journal of Diabetes2014，5，2： | 9 |
| 2 | Angiotensin-converting-enzyme gene insertion/deletion polymorphism andresponse to physical training显示文摘 | Montgomery H Clarkson P Barnard M | 1999 | Lancet1999，353，9152： | 1 |
| 3 | Recollection deficits indysphoric mood:An effect of schematic models and executivemode显示文摘 | Ramponi C Barnard P Nimmo-Smith I | 2004 | Memory2004，12，5： | 1 |
| 4 | The syn- dromic status of sclerosteosis and van Buchem disease 显示文摘 | Beighton P Barnard A Hamersma H | 1984 | Clin Genet1984，125，： | 1 |
| 5 | Cone photoreceptor neuroprotection conferred by CNTF in a novel in vivo model of battlefield retinal laser injury显示文摘 | Aslam SA Davies WIL Singh MS Charbel Issa P Barnard AR Scott RAH | 2013 | Invest Ophthalmol Vis Sci2013，54，8： | 1 |
| 6 | Optimization for training neural nets显示文摘 | Barnard P E | 1992 | IEEE Trans Neural Networks1992，3，2： | 1 |
| 7 | Oxidation mechanisms in Si-Al-O-N ceramics 显示文摘 | Lewis M H Barnard P | 1980 | J Mater Sci1980，15，： | 1 |
| 8 | A nanoparticle catalyst with superior activity for electrooxidation of formic acid 显示文摘 | Waszczuk P Barnard T M C Rice C | 2006 | Electrochem Commun2006，4，： | 1 |
| 9 | Matching Words and Pictures 显示文摘 | BARNARD K DUYGULU P FORSYTH D | 2003 | J Mach Learn Res2003，，3： | 1 |
| 10 | Diet-induced insulin resistance precedes other aspects of the evidence and clinical implications 显示文摘 | Barnard P J Roberts CK Varon SM | 1997 | Am J Clin Nutr1997，66，： | 1 |
| 11 | Laboratory routines cause animal stress显示文摘 | Balcombe J P Barnard N D Sandusky C | 2004 | Lab Animal Sci2004，43，6： | 1 |
| 12 | STAT3-mediated au- tophagy dependence identifies subtypes of breast cancer where au- tophagy inhibition can be efficacious显示文摘 | Maycotte P Gearheart CM Barnard R | 2014 | Cancer Res2014，74，9： | 1 |
| 13 | Matching words and pictures显示文摘 | BARNARD K DUYGULU P De FREITAS N | 2003 | Machine Learning Research2003，1，3： | 1 |
| 14 | Analytical model for rare-earth-doped fiber amplifiers and lasers显示文摘 | C Barnard P Myslinski J Chrostowski | | 0，，： | 1 |
| 15 | Turkey meningo encephalitis in south Africa 显示文摘 | Barnard B J B S Du Preez J H Greyling S P | 1950 | Onderstepoort J Vet Res1950，47，： | 1 |
| 16 | Global change,nitrification,and denitrification:a review显示文摘 | Barnard R Leadley P W Hungate B A | | 0，，01： | 1 |
| 17 | Matching words and pictures显示文摘 | Barnard K Duygulu P Forsyth D | | 0，，： | 1 |
| 18 | Effect of isocaloric low-fat diet on human LAPC-4 prostate cancer xenografts in SCID mice and the IGF axis显示文摘 | Ngo TH Barnard RJ Cohen P | 2003 | Clin Cancer Res2003，9，： | 1 |
| 19 | Effect of isocaloric low-fat diet on human LAPC-4 prostate cancer xenografts in severe combined immunodeficient mice and the insulin-like growth factor axis显示文摘 | Ngo TH Barnard RJ Cohen P | 2003 | Clin Cancer Res2003，9，： | 1 |
| 20 | Structuralinsights into Ail-mediated adhesion in Yersinia pestis显示文摘 | Yamashita S Lukacik P Barnard T J? | 2011 | Structure2011，19，11： | 1 |
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