The effects of the insulin-like growth factor-I aptamer, NBI-31772, on glucose homeostasis in the mouse

2005 ◽  
Vol 83 (7) ◽  
pp. 557-563 ◽  
Author(s):  
Josef V Silha ◽  
Liam J Murphy
Keyword(s):  
Growth Factor ◽  
Specific Activity ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Duration Of Action ◽  
Intravenous Glucose ◽  
Factor I ◽  
Key Words Insulin ◽  
Igf I ◽  
Growth Factor I

The majority of insulin-like growth factor-I (IGF-I) in the adult rodent circulation is bound to high affinity IGF binding proteins. We investigated the changes in IGF-I clearance, blood glucose and plasma insulin levels, and tissue 2-deoxyglucose uptake after intravenous administration of the IGF aptamer, NBI-31772, which selectively competes with IGF-I for binding to the IGFBPs, but has no effect at the IGF-I receptor. Clearance of 125I-IGF-I was significantly increased in NBI-31772-treated mice compared with vehicle-treated mice (t1/2 = 45.0 ± 1.9 vs. 56.3 ± 3.9 min, respectively; p = 0.021). However, NBI-31772 had no significant effect on glucose levels, and no insulin sparing effect was apparent neither under basal conditions nor during an intravenous glucose challenge. The decline in the specific activity after 3H-2-deoxyglucose administration was significantly less rapid in NBI-31772-treated mice compared with controls, suggesting that the IGF-I aptamer had an inhibitory effect on hepatic gluconeogenesis. In contrast, no insulin-like effect was apparent in other tissues examined. 3H-2-deoxyglucose accumulation was similar in all tissues analyzed, including skeletal muscle, which is thought to be particularly sensitive to IGF-I. These data suggest that the IGF-I aptamer affects clearance of radiolabeled IGF-I from the circulation, but has no marked effects on glucose nor insulin homeostasis. The search for hydrophilic IGF aptamers with longer duration of action that could be used in the treatment of diabetes may be rewarding. Key words: insulin resistance, gluconeogenesis, 2-deoxyglucose uptake, glucose clearance.

Mechanism of secretion of plasma insulin-like growth factor-I into milk of lactating goats

1991 ◽  
Vol 131 (3) ◽  
pp. 459-466 ◽  
Author(s):  
C. G. Prosser ◽  
I. R. Fleet ◽  
A. J. Davis ◽  
R. B. Heap
Keyword(s):  
Growth Factor ◽  
Time Course ◽  
Specific Activity ◽  
Gel Filtration ◽  
Free Form ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Lactating Goats ◽  
Igf I ◽  
Growth Factor I

ABSTRACT 125I-Labelled insulin-like growth factor-I (IGF-I) was infused as the free form directly into the pudic artery supplying one gland of lactating goats (n = 6). The infusion was for 60 min and 0·4±0·09% (s.e.m.) of the infusate was secreted into milk from the infused gland during its first passage through that gland. A large proportion of the 125I-labelled IGF-I escaped into the systematic circulation and was secreted into milk of both glands. A total of 5·2±0·4% of infused radioactivity was recovered in milk from both glands from 0 to 720 min. Radioactivity consisted of trichloroacetic acid (TCA)-precipitable and -soluble counts which were shown by gel filtration to be authentic IGF-I and degraded products of the peptide. The amount and time course of TCA-soluble radioactivity in milk from both glands was similar, suggesting degradation of 125I-labelled IGF-I at extramammary sites. Maximum specific activity for 125I-labelled IGF-I in milk from the infused gland was reached 80–120 min after the start of infusion and was 2·5-fold greater than milk from the non-infused gland. The time course of appearance of 125I-labelled IGF-I in milk suggests that transfer was via the transcellular pathway and this was further supported by comparing the pattern of transfer of [14C]sucrose and [14C]amino acids. When excess unlabelled IGF-I was included in the infusate, specific activity in milk from the infused gland was reduced to that of the non-infused gland, indicating a competitive and saturable mechanism of secretion for 125I-labelled IGF-I. Comparison of uptake and secretion of 125I-labelled IGF-I into milk from the non-infused gland with that of endogenous immunoreactive IGF-I suggests that vectorial transport of IGF-I across the mammary gland may be a significant contributor of IGF-I levels in milk. Journal of Endocrinology (1991) 131, 459–466

scholarly journals Fitness, Training, and the Growth Hormone→Insulin-Like Growth Factor I Axis in Prepubertal Girls1

2001 ◽  
Vol 86 (6) ◽  
pp. 2797-2802 ◽  
Author(s):  
Alon Eliakim ◽  
Timothy P. Scheett ◽  
Robert Newcomb ◽  
Subburaman Mohan ◽  
Dan M. Cooper
Keyword(s):  
Growth Factor ◽  
Training Program ◽  
Muscle Volume ◽  
Thigh Muscle ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Prepubertal Girls

We recently demonstrated that a brief endurance type training program led to increases in thigh muscle mass and peak oxygen uptake (V̇O2) in prepubertal girls. In this study, we examined the effect of training on the GH→insulin-like growth factor I (GH→IGF-I) axis, a system known to be involved both in the process of growth and development and in the response to exercise. Healthy girls (mean age 9.17 ± 0.10 yr old) volunteered for the study and were randomized to control (n = 20) and training groups (n = 19) for 5 weeks. Peak V̇O2, thigh muscle volume, and blood samples [for IGF-I, IGF-binding proteins (IGFBP)-1 to -6, and GHBP] were measured. At baseline, IGF-I was significantly correlated with both peak V̇O2 (r = 0.44, P < 0.02) and muscle volume (r = 0.58, P < 0.004). IGFBP-1 was negatively correlated with muscle volume (r = −0.71, P < 0.0001), as was IGFBP-2. IGFBP-4 and -5 were significantly correlated with muscle volume. We found a threshold value of body mass index percentile (by age) of about 71, above which systematic changes in GHBP, IGFBP-1, and peak V̇O2 per kilogram were noted, suggesting decreases in the following: 1) GH function, 2) insulin sensitivity, and 3) fitness. Following the training intervention, IGF-I increased in control (19.4 ± 9.6%, P < 0.05) but not trained subjects, and both IGFBP-3 and GHBP decreased in the training group (−4.2 ± 3.1% and −9.9 ± 3.8%, respectively, P < 0.05). Fitness in prepubertal girls is associated with an activated GH→IGF-I axis, but, paradoxically, early in a training program, children first pass through what appears to be a neuroendocrine state more consistent with catabolism.

Production of insulin-like growth factor I (IGF-I) and IGF-binding proteins by rat intestinal stromal cells in vitro

1998 ◽  
Vol 54 (2) ◽  
pp. 158-166
Author(s):  
R. G. MacDonald ◽  
R. H. McCusker ◽  
D. J. Blackwood ◽  
J. A. Vanderhoof ◽  
J. H. Y. Park
Keyword(s):  
Growth Factor ◽  
Stromal Cells ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Growth Factor I

scholarly journals Expression of the genes encoding the rat renal insulin-like growth factor-I system.

1995 ◽  
Vol 6 (5) ◽  
pp. 1511-1518
Author(s):  
R Rabkin ◽  
M Brody ◽  
L H Lu ◽  
C Chan ◽  
A M Shaheen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Rat Kidney ◽  
Thick Ascending Limb ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Collecting Ducts ◽  
Igf I ◽  
Growth Factor I ◽  
Convoluted Tubules

Insulin-like growth factor-I (IGF-I) modulates renal function, growth, and repair. IGF-I produced in the kidney is one component of the intrarenal IGF-I system comprising the IGF-I receptor (IGF-IR) and six IGF-binding proteins (IGFBP). Because of the physiologic importance of IGF-I and its potential therapeutic properties, the renal sites of mRNA synthesis for IGF-I, IGF-IR, and IGFBP-I through IGFBP-5 were characterized in rat kidney by in situ hybridization. Anatomical heterogeneity was prominent. IGF-I mRNA was present in the thick ascending limb of Henle in the outer medulla, whereas IGF-IR mRNA was diffusely present at low levels throughout the kidney. IGFBP-I mRNA was localized to cells within the distal convoluted tubules as well as the thick ascending limb of Henle. IGFBP-2 mRNA was expressed in glomeruli, medullary ray collecting ducts, pelvic smooth muscle and uroepithelium, and the papilla tip; IGFBP-3 mRNA was localized to the cortical interstitium, whereas IGFBP-4 mRNA was expressed in proximal tubules, medullary ray collecting ducts, and glomeruli. IGFBP-5 was strongly positive throughout the medulla with lesser expression in the distal convoluted tubules and glomeruli. This study highlights the complexity of the intrarenal IGF-I system. The striking heterogeneity of IGFBP gene expression suggests that the various IGFBP may have diverse modulatory effects on the action of IGF-I or discrete effects of their own.

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