Classical PKC is not associated with defective insulin signaling in patients with impaired glucose tolerance.
OBJECTIVE
To investigate the role of insulin signaling defects in impaired glucose tolerance (IGT), we assessed the functionality of the insulin signaling cascade before and after insulin stimulation in both IGT group and control group.


METHODS
Ten IGT subjects and 15 control subjects were recruited for this study. Whole-body insulin-mediated glucose uptake was determined using a euglycemic hyperinsulinemic clamp test. Muscle biopsies were obtained from the vastus lateralis muscle before and after insulin stimulation, to assess the insulin signaling cascade.


RESULTS
The insulin-stimulated incremental changes in phosphorylated IR-beta, IRS, Akt, and GSK-3 beta and in the membrane-associated PKC-zeta protein level were reduced in the IGT group compared with those in the control group (p<0.05). The membrane-associated PKC-lambda protein level was also reduced in the IGT group, but not significantly so (p=0.08). The incremental changes in the protein levels of PKC-alpha, -beta, and -theta were not significantly different between the two groups.


CONCLUSIONS
The subjects with IGT showed decreased membrane-associated PKC-zeta/lambda activity in response to insulin stimulation, as well as defects in early insulin signaling. Our results suggest that membrane-associated PKC-alpha and -beta may not be associated with insulin resistance in IGT.
Kim
Do Min
DM
Department of Internal Medicine, Hanil General Hospital, Seoul, South Korea.
Jang
Hyun Ju
HJ
Han
Seung Jin
SJ
Ha
Eun Suk
ES
Kim
Yun Kyung
YK
Park
Jee Won
JW
Song
Kyoung Eun
KE
Jung
Sun Hye
SH
Ahn
Sang Mi
SM
Choi
Sung E
SE
Kim
Hae Jin
HJ
Kim
Dae Jung
DJ
Lee
Hyun Chul
HC
Lee
Kwan Woo
KW
D000328:Adult; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000201:enzymology* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D011493:Protein Kinase C / Q000097:blood*; D012016:Reference Values; D015398:Signal Transduction
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3