Insulin infusion increases levels of free IGF-I and IGFBP-3 proteolytic activity in patients after surgery

We have studied them effects of insulin on the bioavailability of insulin-l ike growth factor (IGF) I in insulin-resistant patients after surgery. Seru m levels of total IGF-I (tIGF-I), free IGF (fIGF)-I, fIGF-II, and IGF-bindi ng protein (IGFBP) 1 and IGFBP-3 proteolytic activity (IGFBP-3-PA), determi ned on the day before surgery and on the Ist postoperative day, were relate d to insulin sensitivity measured by a hyperinsulinemic, riormoglycemic dam p. Before surgery, the decreased tIGF-I (P < 0.05) in response to insulin i nfusion was accompanied by, an 18% reduction of IGFBP-1 (P < 0.001), while IGFBP-3-PA remained unchanged. Levels of fIGF-I and fIGF-II were not change d by insulin infusions. After surgery, IGFBP-3-PA increased (P < 0.05) duri ng insulin infusion, and this was associated with an increase in tIGF-I (P < 0.001) and fIGF-I (P < 0.01) while no significant change was found in fIG F-II. The reduction in IGFBP-1 in response to insulin infusion was not affe cted by surgery. The change in. IGFBP-3-PA during insulin infusion after su rgery was related to the corresponding change in fIGF-I (r(2) = 0.26, P < 0 .05) and postoperative insulin sensitivity (r(2) = -0.22, P <, 0.05). These data suggest that increased IGFBP-3-PA during insulin infusion after surge ry governs the increased levels of fIGF-I, while insulin-induced suppressio n of IGFBP-1 was not affected by surgery. We propose that, in catabolic, po stoperative patients, increased levels of insulin from exogenous or, possib ly, endogenous sources (nutritionally induced) may be a signal to increase IGF-I bioavailability by increased expression of IGFBP-3-PA to counteract f urther deterioration in glucose metabolism.