Response of tissues to homeostatic signals may play a role in the mediation of nutrient partitioning effects of somatotropin. To investigate this, the effects of exogenous porcine somatotropin (pST) on the metabolic responses to a series of intravenous challenges with dextrose, insulin and epinephrine were examined in twelve crossbred barrows (65 kg). In addition, the hyperinsulinemic-euglycemic clamp technique was used to further explore effects of pST on insulin resistance in eight of these animals. Pigs received daily sc injections of either pituitary-derived pST (120 mug/kg bw) or an equivalent volume of excipient for 28 d. Treatment with pST resulted in a chronic elevation of plasma glucose, insulin and non-esterified fatty acid concentrations and lowered glucagon concentrations. Acute iv challenges of dextrose (100 mg/kg bw), insulin (1.0 mug/kg bw), and epinephrine (2.2 mug/kg bw) were administered on days 21, 22, and 23 of the treatment period, respectively. Hyperinsulinemic-euglycemic clamps were carried out on day 28. Effects of pST were most dramatic for responses associated with insulin. In pST-treated pigs, insulin response to dextrose infusion was enhanced, while glucose response to insulin was attenuated and glucose clearance rate was reduced. During the hyperinsulinemic-euglycemic clamp, dextrose infusion rate required to maintain euglycemia during physiologic elevations of insulin was reduced in pST-treated pigs to 28% of control. In pST-treated pigs, glucose response to epinephrine challenge was halved, while insulin response was increased three-fold. Therefore, one mechanism by which pST shifts the nutrient partition is by altering metabolic responses to homeostatic signals. In growing pigs, this is especially evident for glucose response to insulin,