PMID- 17604977
OWN - NLM
STAT- MEDLINE
DCOM- 20080107
LR  - 20181113
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 50
IP  - 9
DP  - 2007 Sep
TI  - L-glutamine supplementation induces insulin resistance in adipose tissue and 
      improves insulin signalling in liver and muscle of rats with diet-induced 
      obesity.
PG  - 1949-1959
LID - 10.1007/s00125-007-0723-z [doi]
AB  - AIMS/HYPOTHESIS: Diet-induced obesity (DIO) is associated with insulin resistance 
      in liver and muscle, but not in adipose tissue. Mice with fat-specific disruption 
      of the gene encoding the insulin receptor are protected against DIO and glucose 
      intolerance. In cell culture, glutamine induces insulin resistance in adipocytes, 
      but has no effect in muscle cells. We investigated whether supplementation of a 
      high-fat diet with glutamine induces insulin resistance in adipose tissue in the 
      rat, improving insulin sensitivity in the whole animal. MATERIALS AND METHODS: 
      Male Wistar rats received standard rodent chow or a high-fat diet (HF) or an HF 
      supplemented with alanine or glutamine (HFGln) for 2 months. Light microscopy and 
      morphometry, oxygen consumption, hyperinsulinaemic-euglycaemic clamp and 
      immunoprecipitation/immunoblotting were performed. RESULTS: HFGln rats showed 
      reductions in adipose mass and adipocyte size, a decrease in the activity of the 
      insulin-induced IRS-phosphatidylinositol 3-kinase (PI3-K)-protein kinase 
      B-forkhead transcription factor box 01 pathway in adipose tissue, and an increase 
      in adiponectin levels. These results were associated with increases in 
      insulin-stimulated glucose uptake in skeletal muscle and insulin-induced 
      suppression of hepatic glucose output, and were accompanied by an increase in the 
      activity of the insulin-induced IRS-PI3-K-Akt pathway in these tissues. In 
      parallel, there were decreases in TNFalpha and IL-6 levels and reductions in 
      c-jun N-terminal kinase (JNK), IkappaB kinase subunit beta (IKKbeta) and 
      mammalian target of rapamycin (mTOR) activity in the liver, muscle and adipose 
      tissue. There was also an increase in oxygen consumption and a decrease in the 
      respiratory exchange rate in HFGln rats. CONCLUSIONS/INTERPRETATION: Glutamine 
      supplementation induces insulin resistance in adipose tissue, and this is 
      accompanied by an increase in the activity of the hexosamine pathway. It also 
      reduces adipose mass, consequently attenuating insulin resistance and activation 
      of JNK and IKKbeta, while improving insulin signalling in liver and muscle.
FAU - Prada, P O
AU  - Prada PO
AD  - Departamento de Clinica Medica da Universidade Estadual de Campinas, Rua Tessalia 
      Viera de Camargo 126, Campinas, San Paulo, 13083-887, Brazil.
FAU - Hirabara, S M
AU  - Hirabara SM
AD  - Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas da 
      Universidade de Sao Paulo, San Paulo, Brazil.
FAU - Souza, C T de
AU  - Souza CT
AD  - Departamento de Clinica Medica da Universidade Estadual de Campinas, Rua Tessalia 
      Viera de Camargo 126, Campinas, San Paulo, 13083-887, Brazil.
FAU - Schenka, A A
AU  - Schenka AA
AD  - Departamento de Patologia, Universidade Estadual de Campinas, Campinas, San 
      Paulo, Brazil.
FAU - Zecchin, H G
AU  - Zecchin HG
AD  - Departamento de Clinica Medica da Universidade Estadual de Campinas, Rua Tessalia 
      Viera de Camargo 126, Campinas, San Paulo, 13083-887, Brazil.
FAU - Vassallo, J
AU  - Vassallo J
AD  - Departamento de Patologia, Universidade Estadual de Campinas, Campinas, San 
      Paulo, Brazil.
FAU - Velloso, L A
AU  - Velloso LA
AD  - Departamento de Clinica Medica da Universidade Estadual de Campinas, Rua Tessalia 
      Viera de Camargo 126, Campinas, San Paulo, 13083-887, Brazil.
FAU - Carneiro, E
AU  - Carneiro E
AD  - Departamento de Fisiologia, Instituto Biomedico da Universidade Estadual de 
      Campinas, Campinas, San Paulo, Brazil.
FAU - Carvalheira, J B C
AU  - Carvalheira JBC
AD  - Departamento de Clinica Medica da Universidade Estadual de Campinas, Rua Tessalia 
      Viera de Camargo 126, Campinas, San Paulo, 13083-887, Brazil.
FAU - Curi, R
AU  - Curi R
AD  - Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas da 
      Universidade de Sao Paulo, San Paulo, Brazil.
FAU - Saad, M J
AU  - Saad MJ
AD  - Departamento de Clinica Medica da Universidade Estadual de Campinas, Rua Tessalia 
      Viera de Camargo 126, Campinas, San Paulo, 13083-887, Brazil. 
      msaad@fcm.unicamp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20070629
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Insulin)
RN  - 0 (Lipids)
RN  - 0RH81L854J (Glutamine)
RN  - 9005-79-2 (Glycogen)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
RIN - Diabetologia. 2018 Jan;61(1):253. PMID: 29119243
MH  - Animals
MH  - Body Weight/drug effects
MH  - Diet
MH  - *Dietary Supplements
MH  - Glucose/metabolism
MH  - Glutamine/*pharmacology
MH  - Glycogen/biosynthesis
MH  - Insulin/*physiology
MH  - Lipids/biosynthesis
MH  - Liver/drug effects/*physiology
MH  - Male
MH  - Muscle, Skeletal/drug effects/*physiology
MH  - Obesity/*physiopathology
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects/*physiology
EDAT- 2007/07/03 09:00
MHDA- 2008/01/08 09:00
CRDT- 2007/07/03 09:00
PHST- 2007/03/19 00:00 [received]
PHST- 2007/04/30 00:00 [accepted]
PHST- 2007/07/03 09:00 [pubmed]
PHST- 2008/01/08 09:00 [medline]
PHST- 2007/07/03 09:00 [entrez]
AID - 10.1007/s00125-007-0723-z [pii]
AID - 10.1007/s00125-007-0723-z [doi]
PST - ppublish
SO  - Diabetologia. 2007 Sep;50(9):1949-1959. doi: 10.1007/s00125-007-0723-z. Epub 2007 
      Jun 29.