Downregulation of protein kinase C and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes by phorbol esters, glucose, and insulin.
Phorbol esters translocatively activate and subsequently downregulate protein kinase C and insulin-stimulated glucose uptake in rat adipocytes. This study examined the possibility that other translocative activators of protein kinase C in rat adipocytes, e.g., insulin and glucose, provoke similar downregulating effects. Pretreatment of rat adipocytes for 20-24 h with phorbol esters, 3 nM insulin, 20 mM glucose, or 3 nM insulin plus 20 mM glucose resulted in concomitant decreases in protein kinase C and insulin-stimulated (or phorbol ester-stimulated) [3H]-2-deoxyglucose uptake. Downregulating effects of glucose on protein kinase C and insulin-stimulated [3H]-2-deoxyglucose uptake were also evident within 30 min in adipocytes freshly incubated in medium containing 5-20 mM, rather than 0, glucose. These findings confirm that protein kinase C is required during insulin-stimulated glucose uptake and raise the possibility that downregulation of protein kinase C by continued translocative activation of the enzyme may contribute (along with other factors) to impaired responsiveness of the glucose transport system after prolonged insulin and/or glucose treatment.
Ishizuka
T
T
J.A. Haley Veterans Hospital, Tampa, FL 33612.
Cooper
D R
DR
Arnold
T
T
Hernandez
H
H
Farese
R V
RV
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D010703:Phorbol Esters; D003847:Deoxyglucose; D011493:Protein Kinase C; D005947:Glucose