PMID- 28429777
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20220410
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
DP  - 2017 Apr 21
TI  - Interleukin-6 increases the expression and activity of insulin-degrading enzyme.
PG  - 46750
LID - 10.1038/srep46750 [doi]
LID - 46750
AB  - Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and 
      type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 
      interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine 
      on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in 
      the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE 
      expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 
      100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, 
      respectively. In addition, during acute exercise, the inhibition of IL-6 
      prevented an increase in insulin clearance and IDE expression and activity, 
      mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were 
      significantly increased in plasma from humans, after an acute exercise, compared 
      to pre-exercise values. Although the increase in plasma IDE activity was only 
      marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 
      and IDE protein expression, was observed. Our outcomes indicate a novel function 
      of IL-6 on the insulin metabolism expanding the possibilities for new potential 
      therapeutic strategies, focused on insulin degradation, for the treatment and/or 
      prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.
FAU - Kurauti, Mirian A
AU  - Kurauti MA
AD  - Obesity and Comorbidities Research Center (OCRC), Institute of Biology, 
      University of Campinas (UNICAMP), Campinas, SP, Brazil.
FAU - Costa-Junior, Jose M
AU  - Costa-Junior JM
AD  - Obesity and Comorbidities Research Center (OCRC), Institute of Biology, 
      University of Campinas (UNICAMP), Campinas, SP, Brazil.
FAU - Ferreira, Sandra M
AU  - Ferreira SM
AD  - Obesity and Comorbidities Research Center (OCRC), Institute of Biology, 
      University of Campinas (UNICAMP), Campinas, SP, Brazil.
FAU - Santos, Gustavo J
AU  - Santos GJ
AD  - Obesity and Comorbidities Research Center (OCRC), Institute of Biology, 
      University of Campinas (UNICAMP), Campinas, SP, Brazil.
AD  - Department of Physiological Sciences, Center of Biological Sciences, Federal 
      University of Santa Catarina (UFSC), Florianopolis, SC, Brazil.
FAU - Sponton, Carlos H G
AU  - Sponton CHG
AD  - Obesity and Comorbidities Research Center (OCRC), Institute of Biology, 
      University of Campinas (UNICAMP), Campinas, SP, Brazil.
FAU - Carneiro, Everardo M
AU  - Carneiro EM
AD  - Obesity and Comorbidities Research Center (OCRC), Institute of Biology, 
      University of Campinas (UNICAMP), Campinas, SP, Brazil.
FAU - Telles, Guilherme D
AU  - Telles GD
AD  - Exercise Physiology Laboratory (FISEX), Faculty of Physical Education, University 
      of Campinas (UNICAMP), Campinas, SP, Brazil.
FAU - Chacon-Mikahil, Mara P T
AU  - Chacon-Mikahil MPT
AD  - Exercise Physiology Laboratory (FISEX), Faculty of Physical Education, University 
      of Campinas (UNICAMP), Campinas, SP, Brazil.
FAU - Cavaglieri, Claudia R
AU  - Cavaglieri CR
AD  - Exercise Physiology Laboratory (FISEX), Faculty of Physical Education, University 
      of Campinas (UNICAMP), Campinas, SP, Brazil.
FAU - Rezende, Luiz F
AU  - Rezende LF
AD  - Obesity and Comorbidities Research Center (OCRC), Institute of Biology, 
      University of Campinas (UNICAMP), Campinas, SP, Brazil.
AD  - Laboratory of Health Sciences, Department of Physiopathology, State University of 
      Montes Claros (UNIMONTES), Montes Claros, MG, Brazil.
FAU - Boschero, Antonio C
AU  - Boschero AC
AD  - Obesity and Comorbidities Research Center (OCRC), Institute of Biology, 
      University of Campinas (UNICAMP), Campinas, SP, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170421
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Insulin)
RN  - 0 (Interleukin-6)
RN  - EC 3.4.24.56 (Insulysin)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Hep G2 Cells
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulysin/blood/*genetics/metabolism
MH  - Interleukin-6/genetics/metabolism/*pharmacology
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Physical Conditioning, Animal
PMC - PMC5399448
COIS- The authors declare no competing financial interests.
EDAT- 2017/04/22 06:00
MHDA- 2019/07/23 06:00
PMCR- 2017/04/21
CRDT- 2017/04/22 06:00
PHST- 2016/12/22 00:00 [received]
PHST- 2017/03/21 00:00 [accepted]
PHST- 2017/04/22 06:00 [entrez]
PHST- 2017/04/22 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
PHST- 2017/04/21 00:00 [pmc-release]
AID - srep46750 [pii]
AID - 10.1038/srep46750 [doi]
PST - epublish
SO  - Sci Rep. 2017 Apr 21;7:46750. doi: 10.1038/srep46750.