PMID- 20530734
OWN - NLM
STAT- MEDLINE
DCOM- 20101006
LR  - 20211028
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 299
IP  - 3
DP  - 2010 Sep
TI  - Cellular depletion of atypical PKClambda is associated with enhanced insulin 
      sensitivity and glucose uptake in L6 rat skeletal muscle cells.
PG  - E402-12
LID - 10.1152/ajpendo.00171.2010 [doi]
AB  - Atypical protein kinase C (aPKC) isoforms (lambda and zeta) have been implicated 
      in the control of insulin-stimulated glucose uptake in adipose and skeletal 
      muscle, but their precise role in this process remains unclear, especially in 
      light of accumulating evidence showing that, in response to numerous stimuli, 
      including insulin and lipids such as ceramide, activation of aPKCs acts to 
      negatively regulate key insulin-signaling molecules, such as insulin receptor 
      substrate-1 (IRS-1) and protein kinase B (PKB)/cAMP-dependent PKC (Akt). In this 
      study, we have depleted PKClambda in L6 skeletal muscle cells using RNA 
      interference and assessed the effect this has upon insulin action. Muscle cells 
      did not express detectable amounts of PKCzeta. Depletion of PKClambda (>95%) had 
      no significant effect on the expression of proteins participating in insulin 
      signaling [i.e., insulin receptor, IRS-1, phosphatidylinositol 3-kinase (PI 
      3-kinase), PKB, or phosphate and tensin homolog deleted on chromosome 10] or 
      those involved in glucose transport [Akt substrate of 160 kDa, glucose 
      transporter (GLUT)1, or GLUT4]. However, PKClambda-depleted muscle cells 
      exhibited greater activation of PKB/Akt and phosphorylation of its downstream 
      target glycogen synthase kinase 3, in the basal state and displayed greater 
      responsiveness to submaximal doses of insulin with respect to p85-PI 
      3-kinase/IRS-1 association and PKB activation. The increase in basal and 
      insulin-induced signaling resulted in an associated enhancement of basal and 
      insulin-stimulated glucose transport, both of which were inhibited by the PI 
      3-kinase inhibitor wortmannin. Additionally, like RNAi-mediated depletion of 
      PKClambda, overexpression of a dominant-negative mutant of PKCzeta induced a 
      similar insulin-sensitizing effect on PKB activation. Our findings indicate that 
      aPKCs are likely to play an important role in restraining proximal insulin 
      signaling events but appear dispensable with respect to insulin-stimulated 
      glucose uptake in cultured L6 muscle cells.
FAU - Stretton, Clare
AU  - Stretton C
AD  - Sir James Black Centre, Univ. of Dundee, United Kingdom.
FAU - Evans, Ashleigh
AU  - Evans A
FAU - Hundal, Harinder S
AU  - Hundal HS
LA  - eng
GR  - 10/0004045/DUK_/Diabetes UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100608
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Androstadienes)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, rat)
RN  - 0 (Isoenzymes)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (protein kinase C lambda)
RN  - IY9XDZ35W2 (Glucose)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Enzyme Activation
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 4/metabolism
MH  - Immunoblotting
MH  - Insulin Receptor Substrate Proteins/metabolism
MH  - Insulin Resistance/*physiology
MH  - Isoenzymes/*deficiency/genetics/metabolism
MH  - Muscle Fibers, Skeletal/enzymology/metabolism
MH  - Muscle, Skeletal/enzymology/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase C/*deficiency/genetics/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA/chemistry/genetics
MH  - RNA, Small Interfering/pharmacology
MH  - Rats
MH  - Receptor, Insulin/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Wortmannin
EDAT- 2010/06/10 06:00
MHDA- 2010/10/07 06:00
CRDT- 2010/06/10 06:00
PHST- 2010/06/10 06:00 [entrez]
PHST- 2010/06/10 06:00 [pubmed]
PHST- 2010/10/07 06:00 [medline]
AID - ajpendo.00171.2010 [pii]
AID - 10.1152/ajpendo.00171.2010 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2010 Sep;299(3):E402-12. doi: 
      10.1152/ajpendo.00171.2010. Epub 2010 Jun 8.