REGULATION OF LIPOGENESIS IN ADIPOCYTES - INDEPENDENT EFFECTS OF THYROID-HORMONES, CYCLIC-AMP AND INSULIN ON THE UPTAKE OF DEOXY-D-GLUCOSE

Thyroidectomy enhances fat cell phosphodiesterase activity; as a result, the response to lipolytic hormones is markedly reduced. Thyroidectomy also stimulates overall lipogenesis and the uptake of glucose; the present experiments investigated whether there was a correlation between cyclic[c]AMP and glucose uptake. The parameter measured was the transport and phosphorylation (uptake) of deoxy-D-glucose in the presence of 2 modifiers of the cAMP pool: phosphodiesterase inhibitors and the analog, dibutyryl [db] cAMP. The inhibition by methylxanthines and dbcAMP of deoxy-D-glucose uptake observed, was the same in fat cells from normal and thyroidectomized rats; the latter still maintained their enhanced glucose uptake. Thyroid hormones and cAMP evidently control this step by different, separate pathways. Insulin, well known for its lipogenic effect, enhanced deoxy-D-glucose uptake in fat cells from both normal and thyroidectomized rats to the same extent (about 40%). An additive effect of thyroidectomy and insulin on glucose uptake was thus demonstrated. Glucose uptake in the adipocyte is controlled by at least 3 factors: thyroid hormones, cAMP and insulin, each of which can act independently. Maximum glucose uptake is achieved in the presence of a combination of low concentrations of cAMP, of insulin and in the absence of thyroid hormones.