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.