COMPARISON OF TROPHIC EFFECTS OF NOREPINEPHRINE, INSULIN, AND IGF-1 IN MOUSE BROWN ADIPOCYTES

The objective of this work. was to evaluate whether insulin, like nore pinephrine (NE), exerts direct growth effects in brown adipocytes, as assessed by changes in rates of protein labeling with [S-35]methionine . Mouse brown adipocytes isolated by tissue collagenase digestion were incubated for up to 24 h with or without NE in Dulbecco's modified Ea gle's medium with albumin, calf serum, and antibiotics. There was a 40 % cell loss and a 50% decrease in cell content of succinate dehydrogen ase (SDH) activity over 24 h. Both cell recovery and SDH content signi ficantly improved in the presence of NE. In addition, NE increased [S- 35]methionine incorporation into proteins in both cytosolic and mitoch ondrial compartments. These effects of NE were inhibited by propranolo l. Both insulin and insulin-like growth factor-1 (IGF-1) receptors wer e detected in brown adipocytes, with insulin receptors in much greater concentration. Increased protein labeling was observed when brown adi pocytes were incubated for 4 h with 0.2-5 nM insulin in the absence of serum. This effect was small (30% stimulation) compared with the 200- 350% increase observed with NE, and 5 nM IGF-1 had no effect. These re sults indicate direct trophic actions of both NE and insulin in mouse brown adipocytes, with the effects of NE an order of magnitude greater than those of insulin.