Acute metabolic effects and half-lives of intravenously administered insulinlike growth factors I and II in normal and hypophysectomized rats.

Abstract

Insulinlike growth factors (IGF) act qualitatively like insulin on insulin target tissues in vitro. In the circulation in vivo they are bound to specific carrier proteins. In this form or when continuously infused into hypophysectomized (hypox) rats they do not exert acute insulinlike effects on glucose homeostasis. This study definitively shows that intravenous bolus injections of pure IGF I or II act acutely on glucose homeostasis: they lower the blood sugar, enhance the disappearance of U-['4qglucose from serum and increase its incorporation into diaphragm glycogen in normal and hypox rats in the presence of antiinsulin serum. The same effects were obtained with recombinant human IGF I iqjected intravenously either with or without antiinsulin serum into normal rats.Free fatty acid levels decreased transiently only in normal animals. Lipid synthesis from glucose in adipose tissue was not stimulated in hypox and barely stimulated in normal rats.The half-life of injected IGF I or II in normal rats (-4 h) is strikingly different from that in hypophysectomized rats (20-30 min) and appears to depend on the growth hormone-induced 150,000-200,000-mol wt IGF carrier protein that is lacking in hypophysectomized rats.15 min after the bolus serum IGF I and II concentrations were similar to steady state levels during long-term infusion in hypox rats. Free IGF was barely detectable, however, in the infused animals, whereas 40-100% was found free 15 min after the bolus. These observations for the first time confirm the hypothesis that only free IGF, but not the IGF carrier protein complex, is bioavailable to insulin target tissues.

IGF-I increases the recruitment of GLUT4 and GLUT3 glucose transporters on cell surface in hyperthyroidism

“…In a previous study, lipid metabolism was investigated in mouse monocytes after incubation with [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]oleate (33). Of the radioactivity associated with lipid, 80% of oleate was shown to be incorporated into triglycerides, 18% was incorporated into phospholipids, and 2% was recovered as non-esterified fatty acids.…”

“…Insulin-like growth factor-I (IGF-I) has a structural similarity to insulin (3) and its metabolic effects are considered to be similar to those of insulin (4,5). However, in contrast to insulin, IGF-I is ineffective in suppressing hepatic glucose production (6)(7)(8) and has a preferential effect to increase the rates of glycolysis in tissues such as muscle (5).…”

The extracellular regulation of growth factor action.

“…IGF-BPs were first identified as serum proteins that prolonged the half-life of the insulin-like growth factors (IGFs) (Cohen and Nissley, 1976;Kaufmann et al, 1977). The IGF-BPs extend the half-life of IGF in vitro and in vivo from a few minutes (for free IGF) to several hours (Cohen and Nissley, 1976;Zapf et al, 1986). This increase in half-life permits IGF to circulate at levels (-1 ug/ml) two to three orders of magnitude higher than most peptide hormones (Hintz, 1990).…”

Slow Postoperative Decline in Blood Concentration of Insulin-like Growth Factor-1 (IGF-1) in Acromegalic Patients

“…Previous studies reported the half-life of free IGF-1 as around 20-30 min and the half-life of carrier protein-bound IGF-1 as 4 to 15 hr [12,13]. The biological half-life of GH is only about 20 min [14] and the GH level decreases rapidly after successful transsphenoidal adenomectomy [15].…”