Increased protein synthesis response to insulin in fibroblasts treated with the diacylglycerol kinase inhibitor R59022

Insulin stimulated protein synthesis in quiescent 3T3 fibroblasts. This effect of the hormone was greater in the presence of the diacylglycerol kinase inhibitor R59022 (10-5M) over a range of insulin concentrations from 1µU to 1 mU/ml; R59022 increased the sensitivity of cells to insulin. The amount of radioactive diacylglycerol recovered from cells prelabelled with [3H]glycerol was increased transiently in response to insulin; the response was larger and prolonged in cells given the kinase inhibitor. The results (i) support the hypothesis that diacylglycerol production is part of the signal pathway by which insulin stimulates protein synthesis and (ii) suggest that inhibition of diacylglycerol breakdown leads to increased sensitivity to the hormone.