Neurolysin knockout mice generation and initial phenotype characterization.
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 KO mice have increased glucose tolerance, insulin sensitivity, and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semiquantitative peptidomic analysis suggests an 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.
From the Departments of Cell Biology and Development and.
Diogo M L P
DM
Cavalcanti
Pharmacology, Support Center for Research in Proteolysis and Cell Signaling, Biomedical Sciences Institute, University of São Paulo, São Paulo, SP 05508-900, Brazil, the Department of Biophysics, Federal University of São Paulo, São Paulo, SP 04039-032, Brazil.
Leandro M
LM
Castro
From the Departments of Cell Biology and Development and.
José C
JC
Rosa Neto
From the Departments of Cell Biology and Development and.
Marilia
M
Seelaender
From the Departments of Cell Biology and Development and.
Rodrigo X
RX
Neves
the Department of Biophysics, Federal University of São Paulo, São Paulo, SP 04039-032, Brazil.
Vitor
V
Oliveira
the Department of Biochemistry, Support Center for Research in Proteolysis and Cell Signaling, Institute of Chemistry, University of São Paulo, São Paulo, SP 05508-000, Brazil.
Fábio L
FL
Forti
the Special Laboratory of Applied Toxinology, Center of Toxins, Immune Response and Cell Signaling, Butantan Institute, São Paulo, SP 05503-000, Brazil.
Leo K
LK
Iwai
the Institute of Chemistry, State University of Campinas, Campinas, SP 13083-862, Brazil.
Fabio C
FC
Gozzo
the Max-Delbrück-Center for Molecular Medicine, D-13125, Berlin, Germany, and.
Mihail
M
Todiras
the Max-Delbrück-Center for Molecular Medicine, D-13125, Berlin, Germany, and.
Ines
I
Schadock
the Max-Delbrück-Center for Molecular Medicine, D-13125, Berlin, Germany, and the Department of Nutrition, Federal University of Pelotas, Pelotas, RS 96010-610, Brazil.
Carlos C
CC
Barros
the Max-Delbrück-Center for Molecular Medicine, D-13125, Berlin, Germany, and.
Michael
M
Bader
Pharmacology, Support Center for Research in Proteolysis and Cell Signaling, Biomedical Sciences Institute, University of São Paulo, São Paulo, SP 05508-900, Brazil, eferro@usp.br.
Emer S
ES
Ferro
D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D005838:Genotype; D005943:Gluconeogenesis / Q000235:genetics / Q000502:physiology*; D018149:Glucose Intolerance / Q000201:enzymology* / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000502:physiology; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D010641:Phenotype; D010805:Physical Conditioning, Animal / Q000502:physiology; D019289:Pyruvic Acid / Q000378:metabolism
D001786:Blood Glucose; D019289:Pyruvic Acid; D008666:Metalloendopeptidases; C062316:neurolysin
Gluconeogenesis; Glucose Metabolism; Insulin; Intracellular Peptides; Oligopeptidase; Peptidases; Peptides