Antisense DNA downregulates protein kinase C isozymes (beta and alpha) and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes.
Rat adipocytes were treated with antisense dimethoxytrityl pentadecadeoxynucleotides, complementary to mRNA initiation codon regions for alpha and beta isozymes of protein kinase C (PKC). This antisense treatment provoked 50-70% decreases in PKC and insulin-stimulated 2-deoxyglucose uptake, but did not inhibit insulin-stimulated diacylglycerol synthesis. Sense or nonsense oligodeoxynucleotides were without effect on PKC and 2-deoxyglucose uptake. These results suggest that: (i) PKC-alpha and PKC-beta isozymes can be specifically downregulated in rat adipocytes by antisense oligodeoxynucleotides, and (ii) insulin-stimulated glucose transport requires PKC.
Farese
R V
RV
James A. Haley Veterans' Hospital, Department of Internal Medicine, Tampa, FL.
Standaert
M L
ML
Ishizuka
T
T
Yu
B
B
Hernandez
H
H
Waldron
C
C
Watson
J
J
Farese
J P
JP
Cooper
D R
DR
Wickstrom
E
E
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D007329:Insulin Antagonists / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D016373:DNA, Antisense; D007329:Insulin Antagonists; D007527:Isoenzymes; D003847:Deoxyglucose; D011493:Protein Kinase C; D005947:Glucose