Role of pyruvate dehydrogenase and insulin in the regulation of lipogenesis in the lactating mammary gland of the rat during the starved-refed transition.

Administration of insulin with glucose to starved lactating rats, which activates pyruvate dehydrogenase [M. A. Baxter & H. G. Coore (1978) Biochiem. J. 174, 553-561], restored lipogenesis in mammary gland in vivo to 50% of the value observed in refed (2.5 h) rats. The correlations between pyruvate dehydrogenase activity and the rate of lipogenesis persisted in isolated acini. Activation of pyruvate dehydrogenase in vitro with dichloroacetate increased lipogenesis from [6-14C]glucose in acini from starved and refed rats by 250% and 100% respectively. However, in the presence of dichloroacetate, only 70% of the increased flux through pyruvate dehydrogenase was converted into lipid in acini from starved rats, whereas all of the increase could be accounted for as lipid in acini from refed rats. Addition of insulin plus dichloroacetate was required to obtain maximal rates of lipogenesis in acini from starved rats. Similarly, insulin increased the incorporation of [1-14C]acetate into lipid only in acini from starved rats. Although the activity of pyruvate dehydrogenase plays an important role in the control of mammary-gland lipogenesis, the evidence presented suggests a second regulatory site which is insulin-sensitive and is located after the generation of cytosolic acetyl-CoA.