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Neurolysin knockout mice generation and initial phenotype characterization

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Item Type:Article
Title:Neurolysin knockout mice generation and initial phenotype characterization
Creators Name:Cavalcanti, D.M.L.P. and Castro, L.M. and Rosa Neto, J.C. and Seelaender, M. and Neves, R.X. and Oliveira, V. and Forti, F.L. and Iwai, L.K. and Gozzo, F.C. and Todiras, M. and Schadock, I. and Barros, C.C. and Bader, M. and Ferro, E.S.
Abstract:The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln knockout mice (KO) have increased glucose tolerance, insulin sensitivity and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semi-quantitative peptidomic analysis suggests increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity.
Keywords:Gluconeogenesis, Glucose Metabolism, Insulin, Peptidases, Peptides, Intracellular Peptides, Oligopeptidase, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:289
Number:22
Page Range:15426-15440
Date:30 May 2014
Official Publication:https://doi.org/10.1074/jbc.M113.539148
PubMed:View item in PubMed

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