To examine the effects of recombinant human (rh) insulin-like growth factor I (IGF-I), insulin, and saline on metabolic parameters, we studied 20 young nonobese healthy men. Euglycemic clamps with 240-min IGF-I infusions at two doses (49 and 33 pmol.kg-1 x min-1, n = 8 and 12 subjects) were performed and compared with hyperinsulinemic-euglycemic clamps (2.25 pmol.kg-1 x min-1, n = 9). Leucine and glucose kinetics were examined with L-[1-13C]leucine and [3-3H]glucose. Glucose rate of appearance (Ra) declined equivalently in the 49 pmol.kg-1.min-1 IGF-I and insulin clamps but remained at basal levels during the 33 pmol.kg-1 x min-1 IGF-I infusions. In contrast, Rd of glucose was increased by 176% in the 49 pmol.kg-1 x min-1 IGF-I and 78% in the 33 pmol.kg-1 x min-1 IGF-I infusions. Furthermore, to prevent hypoglycemia after the termination of both rhIGF-I infusions, it was necessary to infuse glucose for an additional 2-20 h. Ra of leucine was suppressed significantly by both IGF-I and insulin, whereas leucine oxidation was not affected by either hormone. Therefore, the rate of disappearance of leucine expressed as the difference between Ra and oxidation rates was significantly reduced in all clamps. In addition, IGF-I significantly suppressed beta-cell secretion without affecting the other glucoregulatory hormones. In contrast to insulin, IGF-I had no apparent effect on lipolysis, as measured by changes in nonesterified fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)