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Identification of Four Mouse Diabetes Candidate Genes Altering β-Cell Proliferation
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نویسنده
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kluth o. ,matzke d. ,kamitz a. ,jähnert m. ,vogel h. ,scherneck s. ,schulze m. ,staiger h. ,machicao f. ,häring h.-u. ,joost h.-g. ,schürmann a.
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منبع
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plos genetics - 2015 - دوره : 11 - شماره : 9
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چکیده
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Beta-cell apoptosis and failure to induce beta-cell regeneration are hallmarks of type 2-like diabetes in mouse models. here we show that islets from obese,diabetes-susceptible new zealand obese (nzo) mice,in contrast to diabetes-resistant c57bl/6j (b6)-ob/ob mice,do not proliferate in response to an in-vivo glucose challenge but lose their beta-cells. genome-wide rnaseq based transcriptomics indicated an induction of 22 cell cycle-associated genes in b6-ob/ob islets that did not respond in nzo islets. of all genes differentially expressed in islets of the two strains,seven mapped to the diabesity qtl nob3,and were hypomorphic in either nzo (lefty1,apoa2,pcp4l1,mndal,slamf7,pydc3) or b6 (ifi202b). adenoviral overexpression of lefty1,apoa2,and pcp4l1 in primary islet cells increased proliferation,whereas overexpression of ifi202b suppressed it. we conclude that the identified genes in synergy with obesity and insulin resistance participate in adaptive islet hyperplasia and prevention from severe diabetes in b6-ob/ob mice. © 2015 kluth et al.
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آدرس
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department of experimental diabetology,german institute of human nutrition potsdam-rehbruecke,nuthetal,germany,german center for diabetes research (dzd),neuherberg, Germany, department of experimental diabetology,german institute of human nutrition potsdam-rehbruecke,nuthetal,germany,german center for diabetes research (dzd),neuherberg, Germany, department of experimental diabetology,german institute of human nutrition potsdam-rehbruecke,nuthetal,germany,german center for diabetes research (dzd),neuherberg, Germany, department of experimental diabetology,german institute of human nutrition potsdam-rehbruecke,nuthetal,germany,german center for diabetes research (dzd),neuherberg, Germany, department of experimental diabetology,german institute of human nutrition potsdam-rehbruecke,nuthetal,germany,german center for diabetes research (dzd),neuherberg, Germany, department of experimental diabetology,german institute of human nutrition potsdam-rehbruecke,nuthetal,germany,german center for diabetes research (dzd),neuherberg,germany,institute of pharmacology and toxicology,university of braunschweig,braunschweig, Germany, german center for diabetes research (dzd),neuherberg,germany,department of molecular epidemiology,german institute of human nutrition potsdam-rehbrueckenuthetal, Germany, german center for diabetes research (dzd),neuherberg,germany,department of internal medicine,university hospital tübingen,tübingen,germany,institute for diabetes research and metabolic diseases of the helmholtz center munich at the university of tübingen,tübingen, Germany, german center for diabetes research (dzd),neuherberg,germany,institute for diabetes research and metabolic diseases of the helmholtz center munich at the university of tübingen,tübingen, Germany, german center for diabetes research (dzd),neuherberg,germany,department of internal medicine,university hospital tübingen,tübingen,germany,institute for diabetes research and metabolic diseases of the helmholtz center munich at the university of tübingen,tübingen, Germany, german center for diabetes research (dzd),neuherberg,germany,department of pharmacology,german institute of human nutrition potsdam-rehbruecke,nuthetal, Germany, department of experimental diabetology,german institute of human nutrition potsdam-rehbruecke,nuthetal,germany,german center for diabetes research (dzd),neuherberg, Germany
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Authors
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