Insulin-like Growth Factor II Induces DNA Synthesis in Fetal Ventricular Myocytes In Vitro

1996 ◽  
Vol 79 (4) ◽  
pp. 716-726 ◽  
Author(s):  
Qingquan Liu ◽  
Huajun Yan ◽  
Nicola J. Dawes ◽  
Giuliano A. Mottino ◽  
Joy S. Frank ◽  
...  
Development ◽  
1989 ◽  
Vol 106 (3) ◽  
pp. 543-554 ◽  
Author(s):  
A.L. Brice ◽  
J.E. Cheetham ◽  
V.N. Bolton ◽  
N.C. Hill ◽  
P.N. Schofield

The insulin-like growth factors are broadly distributed in the human conceptus and are thought to play a role in the growth and differentiation of tissues during development. Using in situ hybridization we have shown that a wide variety of specific cell types within tissues express the gene for insulin-like growth factor II at times of development from 18 days to 14 weeks of gestation. Examination of blastocysts produced by in vitro fertilization showed no expression, thus bracketing the time of first accumulation of IGF-II mRNA to between 5 and 18 days postfertilization. The pattern of IGF-II expression shows specific age-related differences in different tissues. In the kidney, for example, expression is found in the cells of the metanephric blastema which is dramatically reduced as the blastema differentiates. The reverse is also seen, and we have noted an increase in expression of IGF-II in the cytotrophoblast layer of the placenta with gestational age. The sites of expression do not correlate with areas of either high mitotic activity or specific types of differentiation, but the observed pattern of expression in the kidney, adrenal glands and liver suggests an explanation for the abnormally high IGF-II mRNA expression in developmental tumours such as Wilms' tumour.


1994 ◽  
Vol 300 (3) ◽  
pp. 781-785 ◽  
Author(s):  
B Burguera ◽  
C W Elton ◽  
J F Caro ◽  
E B Tapscott ◽  
W J Pories ◽  
...  

Although the growth-promoting effects of insulin-like growth factor II (IGF-II) have been intensively studied, the acute actions of this hormone on glucose metabolism have been less well evaluated, especially in skeletal muscle of humans. We and other groups have shown that IGFs reduce glycaemic levels in humans and stimulate glucose uptake in rat muscle. The purpose of the present study was to evaluate the effect of IGF-II on glucose transport in muscle of normal and obese patients with and without non-insulin-dependent diabetes mellitus (NIDDM), as well as to identify the receptor responsible for this action. 2-Deoxyglucose transport was determined in vitro using a muscle-fibre strip preparation. IGF-II were investigated in biopsy material of rectus abdominus muscle taken from lean and obese patients and obese patients with NIDDM at the time of surgery. In the lean group, IGF-II (100 nM) stimulated glucose transport 2.1-fold, which was slightly less than stimulation by insulin (2.8-fold) at the same concentration. Binding of IGF-II was approx. 25% of that of insulin at 1 nM concentrations of both hormones. Obesity with or without NIDDM significantly reduced IGF-II-stimulated glucose uptake compared with the lean group. In order to explore which receptor mediated the IGF-II effect, we compared glucose uptake induced by IGF-II and two IGF-II analogues: [Leu27]IGF-II, with high affinity for the IGF-II/Man 6-P receptor but markedly reduced affinity for the IGF-I and insulin receptors, and [Arg54,Arg55]IGF-II was similar to that of IGF-II, whereas [Leu27]IGF-II had a very diminished effect. Results show that IGF-II is capable of stimulating muscle glucose uptake in lean but not in obese subjects and this effect seems not to be mediated via an IGF-II/Man 6-P receptor.


1992 ◽  
Vol 286 (2) ◽  
pp. 561-565 ◽  
Author(s):  
S J Bevan ◽  
M Parry-Billings ◽  
E Opara ◽  
C T Liu ◽  
D B Dunger ◽  
...  

The effect of insulin-like growth factor II (IGF II) on the rates of lactate formation, glycogen synthesis and glucose transport in the presence of a range of concentrations of insulin were investigated using an isolated preparation of rat skeletal muscle. IGF II, at a concentration of 65 ng/ml, caused a small but significant increase in the rates of these processes at a basal physiological insulin concentration (10 muunits/ml), but was without effect in the presence of 1, 100, 1000 or 10,000 muunits of insulin/ml. Hence IGF II increased the insulin sensitivity of this tissue. This effect was removed if the incubation medium was supplemented with an equimolar concentration of IGF binding protein 1 (BP1). It is suggested that changes in the concentration of IGF II and/or BP1 may regulate glucose uptake and metabolism in skeletal muscle and have physiological significance in the control of blood glucose level.


1997 ◽  
Vol 326 (2) ◽  
pp. 407-413 ◽  
Author(s):  
Marcos R. DIFALCO ◽  
L. Fernando CONGOTE

We have found that a slightly modified insulin-like growth factor II (IGF II) consisting of a chimaera of bombyxin and human IGF II (BOMIGF) is properly secreted in insect cells by using the baculovirus expression system. Human interleukin 3 (IL-3) was attached to the C-terminal amino acid residue of BOMIGF with peptide linkers containing five or twelve residues. Only the chimaera with the 12-residue linker had biological activities of both IGF II and IL-3. The chimaera had a significantly higher mitogenic activity than IL-3 in cell cultures of the human haemopoietic cell line TF-1 and its effect could be observed even at femtomolar concentrations. It was also able to stimulate thymidine incorporation in IGF II-dependent bovine fetal erythroid cells. The chimaera significantly increased the number of macroscopic haemopoietic colonies in cultures of human peripheral blood in comparison with IL-3 or mixtures of IL-3 and BOMIGF in vitro. Subcutaneous injection of a BOMIGF–mouse IL-3 chimaera in normal C57BL/6 mice resulted in a significant increase of the number of spleen stem cells producing macroscopic haemopoietic colonies. This new system for the biosynthesis of IGF–cytokine fusion proteins in insect cells might prove advantageous for the low-cost and high-yield production of molecules with complementary or synergistic biological activities.


1996 ◽  
Vol 103 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Timothy S. Vincent ◽  
Debra J. Hazen-Martin ◽  
A.Julian Garvin

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