scholarly journals Comparative binding of bovine, human and rat insulin-like growth factors to membrane receptors and to antibodies against human insulin-like growth factor-1

1986 ◽  
Vol 233 (1) ◽  
pp. 215-221 ◽  
Author(s):  
L C Read ◽  
F J Ballard ◽  
G L Francis ◽  
R C Baxter ◽  
C J Bagley ◽  
...  
Keyword(s):  
Growth Factors ◽  
Polyclonal Antiserum ◽  
Competitive Binding ◽  
Membrane Receptors ◽  
Binding Studies ◽  
Comparative Binding ◽  
Placental Membranes ◽  
Insulin Like Growth Factors

The immunological properties of human, bovine and rat insulin-like growth factors (IGF) and insulin were compared in competitive binding studies with Tr10 and NPA polyclonal antisera raised in rabbits against human IGF-1. Bovine IGF-1 was 11-19% as effective as human IGF-1 in competing for binding with 125I-labelled human IGF-1, whereas IGF-2 reacted poorly and insulin did not compete. Similar competitive binding curves were obtained with the mouse monoclonal anti-(human IGF-1) antibody 3D1, except that bovine IGF-1 showed a severalfold greater affinity for the monoclonal antibody than for either polyclonal antiserum. Membranes isolated from human placenta, sheep placenta and foetal-human liver were used as sources of cellular receptors. In human placental membranes, most of the binding of IGF-1 tracers could be attributed to a type-1 receptor, because insulin inhibited up to 65% of tracer binding. The other two tissues apparently contain only type-2 receptors, as evidenced by the very low potency of bovine or human IGF-1 in competing for binding with IGF-2 tracers and the absence of any competition by insulin. In competition for binding with labelled bovine or human IGF-1 to human placental membranes, bovine IGF-1 had a similar potency to human IGF-1, whereas bovine IGF-1 was more potent in binding studies with tissues rich in type-2 receptors. Rat IGF-2 was considerably less effective than human IGF-2 in competition for receptors on any of the membrane preparations.

scholarly journals Specific binding of insulin-like growth factors 1 and 2 to the type 1 and type 2 receptors respectively

1988 ◽  
Vol 249 (3) ◽  
pp. 721-726 ◽  
Author(s):  
F J Ballard ◽  
M Ross ◽  
F M Upton ◽  
G L Francis
Keyword(s):  
Growth Factors ◽  
Specific Binding ◽  
Protein A ◽  
Cell Types ◽  
Bovine Insulin ◽  
Lung Fibroblasts ◽  
Ligand Interactions ◽  
Insulin Like Growth Factors

1. Competitive binding and receptor cross-linking experiments have been used to examine the receptor-ligand interactions between three bovine insulin-like growth factors (IGF) and monolayer cultures of myoblasts and fibroblasts. 2. Labelled IGF-2 bound predominantly to the type 2 receptor with negligible label cross-linked to the type 1 receptor, notwithstanding the ability of IGF-2 to compete effectively for the binding of IGF-1 to the type 1 receptor. Approx. 100-fold higher concentrations of IGF-1 or the N-terminal truncated (des-Gly-Pro-Glu) IGF-1 (-3N:IGF-1) were required to produce competition equivalent to IGF-2. 3. All IGF peptides, but especially IGF-1, enhanced the binding of labelled IGF-2 to the type 2 receptor of lung fibroblasts. This unusual effect was probably a consequence of the displacement of labelled IGF-2 otherwise bound to a medium protein, a conclusion supported by the demonstration of a 38 kDa membrane protein cross-linked to labelled IGF-2. 4. Both IGF-1 and -3N:IGF-1 bound only to the type 1 IGF receptor in L6 myoblasts, rat vascular smooth-muscle cells and human lung fibroblasts. The peptides competed for labelled IGF-1 binding with potencies in the order -3N:IGF-1 greater than IGF-1 greater than IGF-2 much greater than insulin. Since the IGF peptides were equipotent in skin fibroblasts, it was proposed that the apparently higher affinity of -3N:IGF-1 for receptors in the other cell types was instead a consequence of a low affinity of this peptide for the competing 38 kDa binding protein.

Insulin-like growth factors and the multiplication of Tera-2, a human teratoma-derived cell line

1988 ◽  
Vol 90 (3) ◽  
pp. 475-484
Author(s):  
C. Biddle ◽  
C.H. Li ◽  
P.N. Schofield ◽  
V.E. Tate ◽  
B. Hopkins ◽  
...  
Keyword(s):  
Growth Factors ◽  
Cell Line ◽  
Serum Free Medium ◽  
Free Medium ◽  
Maximal Stimulation ◽  
Igf Receptors ◽  
Igf I ◽  
Insulin Like Growth Factors

A human teratoma cell line (Tera-2) was grown in serum-free medium, and the population multiplication was stimulated by the addition of somatomedins/insulin-like growth factors (IGFs). Both IGF-I and IGF-II gave maximal stimulation when added daily at 10 ng ml-1. The IGFs did not substantially change the labelling index of the cells, and the IGFs appeared to exert their effect on population multiplication by increasing cell survival. Membranes isolated from Tera-2 cells displayed both type 1 and type 2 IGF receptors.

scholarly journals Binding properties and biological potencies of insulin-like growth factors in L6 myoblasts

1986 ◽  
Vol 233 (1) ◽  
pp. 223-230 ◽  
Author(s):  
F J Ballard ◽  
L C Read ◽  
G L Francis ◽  
C J Bagley ◽  
J C Wallace
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Radioligand Binding ◽  
Cross Linking ◽  
Protein Accumulation ◽  
Igf Receptor ◽  
H Protein ◽  
Insulin Like Growth Factors

Protein synthesis in rat L6 myoblasts is stimulated and protein breakdown inhibited in a co-ordinate manner by insulin-like growth factors (IGF) or insulin. For both processes, bovine IGF-1 was somewhat more potent than human IGF-1, which was effective at a tenth the concentration of insulin, rat IGF-2 or human IGF-2. A similar order of potency is noted when DNA synthesis or protein accumulation is monitored over a 24 h period, but between 20- and 50-fold higher concentrations of each growth factor are required than those needed to produce effects in the 4 h protein-synthesis or -breakdown measurements. Binding experiments with labelled human or bovine IGF-1 as ligand demonstrated competition at concentrations of IGF-2, especially human IGF-2, lower than that of either IGF-1 preparation. This pattern was much more pronounced when the radioligand was either human IGF-2 or rat IGF-2. Insulin competed 10-15% for the binding of labelled IGF-1, but not at all with labelled IGF-2. Ligand-receptor cross-linking experiments showed that labelled bovine IGF-1 bound approximately equally to the type 1 IGF receptor (Mr 130000 after reduction) and to the type 2 IGF receptor (Mr 270000 after reduction), and that unlabelled IGF-1 competed equally with radioligand binding to both receptors. On the other hand, rat IGF-2 competed more effectively for binding to the type-2 receptor, and insulin competed only for binding to the type-1 receptor. Further cross-linking experiments with rat IGF-2 as radioligand demonstrated binding only to the type-2 receptor and to proteins with Mr values after reduction of 230000 and 200000. This binding was prevented by high rat IGF-2 concentrations, less effectively by bovine IGF-1 and not at all by insulin. The apparently conflicting biological potencies and receptor binding of the different growth factors can be explained if all the biological actions are mediated via the type-1 IGF receptor, rather than through the abundant type-2 receptor.

Effects of insulin-like growth factors on chick embryo hepatocytes

1985 ◽  
Vol 108 (2) ◽  
pp. 237-244 ◽  
Author(s):  
U. Widmer ◽  
Ch. Schmid ◽  
J. Zapf ◽  
E. R. Froesch
Keyword(s):  
Growth Factors ◽  
Chick Embryo ◽  
Ornithine Decarboxylase ◽  
Biological Effects ◽  
Competitive Binding ◽  
Decarboxylase Activity ◽  
Ornithine Decarboxylase Activity ◽  
Igf I ◽  
Embryo Liver ◽  
Insulin Like Growth Factors

Abstract. Biological effects of insulin-like growth factors (IGF) I and II on primary cultures of chick embryo liver cells have been investigated and compared 1) with the biological effect of insulin and 2) with competitive binding of the three hormones to their respective binding sites. IGF I and II stimulate the incorporation of d[U-14C]-glucose into liver cell glycogen in a time- and dose-dependent manner, but with a 5–10-fold lower potency than insulin: Both IGFs also lead to enhanced incorporation of 5-[3H]uridine and l[U-14C]valine into trichloroacetic acid (TCA) insoluble material and to activation of ornithine decarboxylase activity. Their potency in stimulating RNA synthesis and ornithine decarboxylase activity is comparable to that of insulin. Protein synthesis is maximally stimulated at 3 nm by all three hormones. In the competitive binding studies, IGF I and II are 10-fold less potent than insulin in competing for [125I]insulin binding, but 100-fold more potent than insulin in competing for [125I]IGF I or II binding. These studies show that IGF I and II stimulate the same metabolic indices as insulin in the chick embryo liver. By comparing these biological effects with competitive binding data it appears that IGFs act on glucose metabolism in the chick embryo liver via the insulin receptor, whereas stimulation of growth indices by IGFs and insulin appears to be mediated by their own specific receptors.

scholarly journals A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors

2013 ◽  
Vol 2013 ◽  
pp. 1-37 ◽  
Author(s):  
Rosalyne L. Westley ◽  
Felicity E. B. May
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factors ◽  
Diabetes Mellitus Type 2 ◽  
Diabetes Mellitus Type ◽  
Type I ◽  
Hormone Production ◽  
Type I Igf Receptor ◽  
High Concentrations ◽  
Insulin Like Growth Factors

Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.

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