Insulin and IGF-I induce pronounced hypertrophy of skeletal myofibers in tissue culture

1991 ◽  
Vol 260 (3) ◽  
pp. C475-C484 ◽  
Author(s):  
H. H. Vandenburgh ◽  
P. Karlisch ◽  
J. Shansky ◽  
R. Feldstein
Keyword(s):  
Tissue Culture ◽  
Growth Factor ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Insulin Like Growth Factor ◽  
Cell Hyperplasia ◽  
Factor Ii ◽  
Igf I ◽  
Collagen Gel Matrix

Skeletal myofibers differentiated from primary avian myoblasts in tissue culture can be maintained in positive nitrogen balance in a defined serum-free medium for at least 6-7 days when embedded in a three-dimensional collagen gel matrix. Incubation of established myofiber cultures for 3-7 days with insulin (1 microM) or insulin-like growth factor I (IGF-I, 32 nM) stimulates both cell hyperplasia and myofiber hypertrophy. Mean myofiber diameter increases 71-98%. Insulin-like growth factor II stimulates cell hyperplasia but not myofiber hypertrophy. Cell growth results from a 42-62% increase in total protein synthesis and a 28-38% decrease in protein degradation. Myosin heavy-chain content increases 183-258% because of a 55% stimulation of myosin synthesis and 33-61% inhibition of degradation. Associated with myofiber hypertrophy is a 87-148% increase in the number of myofiber nuclei per unit myofiber length. The results indicate that insulin and IGF-I, but not IGF-II, can induce rapid myofiber hypertrophy in vitro, most likely by stimulating myoblast proliferation and/or fusion to established myofibers.

Effects of insulin-like growth factor-II on growth hormone release from human somatotrophinoma cells in vitro

1991 ◽  
Vol 129 (3) ◽  
pp. 447-451 ◽  
Author(s):  
P. E. Harris ◽  
M. Daniels ◽  
R. A. James ◽  
S. J. Turner ◽  
J. Dewar ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hormone Release ◽  
Insulin Like Growth Factor ◽  
Inhibitory Effects ◽  
Variable Effect ◽  
Gh Secretion ◽  
Factor Ii ◽  
Igf I ◽  
Stimulation Of

ABSTRACT Insulin-like growth factor-I (IGF-I) and IGF-II receptors have previously been demonstrated on membranes prepared from human somatotrophinomas. IGF-I has been shown to have a variable effect on GH secretion by these tumours in vitro. The effects of purified IGF-II on GH secretion have not been described. We have studied the direct actions of human recombinant IGF-II on GH release from eight somatotrophinomas cultured in vitro. Somatotrophinoma cells were cultured as monolayers at a density of 105 cells/0·5 ml. Treatment with IGF-II for 4 and 24 h resulted in discrete inhibitory effects on GH release from two tumours (tumour 5:4 h, IGF-II 0·5 nmol/l; tumour 2; 24 h, IGF-II 1 nmol/l). Treatment with IGF-II for 24 h resulted in significant inhibitory effects on GH release from one tumour over a range of concentrations tested (IGF-II 0·5–10 nmol/l). Addition of human GH-releasing factor (hGRF)(1–44) (20 nmol/l) for 4 and 24 h resulted in stimulation of GH release by five tumours. Two tumours demonstrated significant inhibitory effects of IGF-II on GRF-stimulated GH release (tumour 2: 24 h, IGF-II 1–5 nmol/l; tumour 3; 4 h, IGF-II 5 nmol/l; 24 h, IGF-II 0·5–50 nmol/l). These data emphasize the heterogeneity of somatotrophinomas in terms of their response to modulators of GH secretion. IGF-II does not appear to have a modulatory role on GH release by most somatotrophinomas. Journal of Endocrinology (1991) 129, 447–451

scholarly journals Targeting hepatocyte growth factor in epithelial–stromal interactions in an in vitro experimental model of human periodontitis

Odontology ◽  
2021 ◽  
Author(s):  
Yoko Yamaguchi ◽  
Akira Saito ◽  
Masafumi Horie ◽  
Akira Aoki ◽  
Patrick Micke ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Neutralizing Antibody ◽  
Chronic Inflammatory Disease ◽  
Collagen Degradation ◽  
Hepatocyte Growth

AbstractPeriodontitis is a chronic inflammatory disease leading to progressive connective tissue degradation and loss of the tooth-supporting bone. Clinical and experimental studies suggest that hepatocyte growth factor (HGF) is involved in the dysregulated fibroblast–epithelial cell interactions in periodontitis. The aim of this study was to explore effects of HGF to impact fibroblast-induced collagen degradation. A patient-derived experimental cell culture model of periodontitis was applied. Primary human epithelial cells and fibroblasts isolated from periodontitis-affected gingiva were co-cultured in a three-dimensional collagen gel. The effects of HGF neutralizing antibody on collagen gel degradation were tested and transcriptome analyses were performed. HGF neutralizing antibody attenuated collagen degradation and elicited expression changes of genes related to extracellular matrix (ECM) and cell adhesion, indicating that HGF signaling inhibition leads to extensive impact on cell–cell and cell–ECM interactions. Our study highlights a potential role of HGF in periodontitis. Antagonizing HGF signaling by a neutralizing antibody may represent a novel approach for periodontitis treatment.

Measurement of Human Igf-II Using Sephacryl Extraction: A Rapid and Reliable Assay Method

1996 ◽  
Vol 33 (3) ◽  
pp. 201-208 ◽  
Author(s):  
Barbara H Mason ◽  
Michele A Tatnell ◽  
Ian M Holdaway
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Complete Removal ◽  
Assay Method ◽  
Insulin Like Growth Factor ◽  
Serum Concentrations ◽  
Igf Binding Proteins ◽  
Factor Ii ◽  
Igf I ◽  
Igfbp 3

Measurement of insulin-like growth factor II (IGF-II) in human serum is complicated by the presence of IGF binding proteins and usually involves cumbersome extraction procedures followed by radioimmunoassay. We have utilized an extraction process developed for measuring insulin-like growth factor II in ovine serum using Sephacryl HR100, and have applied this to the extraction of human samples followed by radioimmunoassay for human IGF-II. The assay yielded 98% recovery of unlabelled IGF-II, parallelism between dilutions of eluate and the standard curve, complete removal of binding proteins and near-complete removal of IGF-I, and intra- and interassay coefficients of variation of 5% and 9%, respectively. The normal range for serum IGF-II in women was 490–1056 μg/L, and IGF-II levels were positively correlated with serum concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) but not with IGF-I levels. Mean serum concentrations of IGF-II were reduced below normal in a number of hypopituitary patients and children with short stature and IGF-II concentrations in these subjects correlated positively with IGF-I and IGFBP-3. In acromegalic patients IGF-II levels were usually normal and were negatively correlated with IGF-I concentrations. From our experience with the above results the present assay appears particularly suitable for clinical measurements and research projects where high sample throughput is required.

Longitudinal bone growth in vitro: effects of insulin-like growth factor I and growth hormone

1991 ◽  
Vol 124 (5) ◽  
pp. 602-607 ◽  
Author(s):  
Ben A. A. Scheven ◽  
Nicola J. Hamilton
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Growth ◽  
Long Bone ◽  
Long Bones ◽  
Insulin Like Growth Factor ◽  
Serum Free ◽  
Factor I ◽  
Igf I

Abstract. Longitudinal growth was studied using an in vitro model system of intact rat long bones. Metatarsal bones from 18- and 19-day-old rat fetuses, entirely (18 days) or mainly (19 days) composed of chondrocytes, showed a steady rate of growth and radiolabelled thymidine incorporation for at least 7 days in serum-free media. Addition of recombinant human insulin-like growth factor-I to the culture media resulted in a direct stimulation of the longitudinal growth. Recombinant human growth hormone was also able to stimulate bone growth, although this was generally accomplished after a time lag of more than 2 days. A monoclonal antibody to IGF-I abolished both the IGF-I and GH-stimulated growth. However, the antibody had no effect on the growth of the bone explants in control, serum-free medium. Unlike the fetal long bones, bones from 2-day-old neonatal rats were arrested in their growth after 1-2 days in vitro. The neonatal bones responded to IGF-I and GH in a similar fashion as the fetal bones. Thus in this study in vitro evidence of a direct effect of GH on long bone growth via stimulating local production of IGF by the growth plate chondrocytes is presented. Furthermore, endogenous growth factors, others than IGFs, appear to play a crucial role in the regulation of fetal long bone growth.

Temporal changes in the expression of the insulin-like growth factor II gene associated with tissue maturation in the human fetus

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
Keyword(s):  
Growth Factor ◽  
Cell Types ◽  
Specific Cell ◽  
Insulin Like Growth Factor ◽  
Vitro Fertilization ◽  
Age Related ◽  
Factor Ii ◽  
Metanephric Blastema

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.

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 ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Ventricular Myocytes ◽  
Insulin Like Growth Factor ◽  
Factor Ii

scholarly journals Stimulation of glucose uptake by insulin-like growth factor II in human muscle is not mediated by the insulin-like growth factor II/mannose 6-phosphate receptor

1994 ◽  
Vol 300 (3) ◽  
pp. 781-785 ◽  
Author(s):  
B Burguera ◽  
C W Elton ◽  
J F Caro ◽  
E B Tapscott ◽  
W J Pories ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Dependent Diabetes Mellitus ◽  
Obese Patients ◽  
Insulin Like Growth Factor ◽  
Biopsy Material ◽  
Factor Ii ◽  
Lean Group

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.

Hypoglycemia in a dog with a leiomyoma of the gastric wall producing an insulin-like growth factor II-like peptide

1995 ◽  
Vol 132 (6) ◽  
pp. 744-750 ◽  
Author(s):  
Andrea Boari ◽  
Antonina Barreca ◽  
Gilberto E Bestetti ◽  
Francesco Minuto ◽  
Massimiliano Venturoli
Keyword(s):  
Growth Factor ◽  
Tumor Tissue ◽  
Tissue Concentration ◽  
Molecular Form ◽  
Islet Cell Tumor ◽  
Gastric Wall ◽  
Insulin Like Growth Factor ◽  
Factor Ii ◽  
Igf I ◽  
Tumor Hypoglycemia

Boari A, Barreca A, Bestetti GE, Minuto F, Venturoli M. Hypoglycemia in a dog with a leiomyoma of the gastric wall producing an insulin-like growth factor II-like peptide. Eur J Endocrinol 1995;132:744–50. ISSN 0804–4643 A 12-year-old mixed-breed male dog was referred to the Clinica Medica Veterinaria of Bologna University for recurrent episodes of seizures due to hypoglycemia with abnormally low plasma insulin levels (18 pmol/l), Resection of a large leiomyoma (780 g) of the gastric wall resulted in a permanent resolution of the hypoglycemic episodes. Insulin-like growth factors I and II (IGF-I and -II) were measured by RIA in serum before and after surgery and in tumor tissue. Results were compared to the serum concentration of 54 normal and to the tissue concentration observed in eight non-hypoglycemic dog gastric wall extracts. Before surgery, circulating immunoreactive IGF-I was 0.92 nmol/l, which is significantly lower than the control values (16.92 ± 8.44 nmol/l, range 3.53–35.03), while IGF-II was 152 nmol/l, which is significantly higher than the control values (42.21 ± 3.75. range 31.99–50.74). After surgery, IGF-I increased to 6.80 nmol/l while IGF-II decreased to 45.52 nmol/l, Tumor tissue IGF-II concentration was higher than normal (5.66 nmol/kg tissue as compared to a range in normal gastric wall tissue of 1.14–3.72 nmol/kg), while IGF-I was 0.08 nmol/kg tissue, which is close to the lowest normal value (range in controls, 0.08–1.18 nmol/kg). Partial characterization of IGF-II immunoreactivity extracted from tissue evidenced a molecular weight similar to that of mature IGF-II thus excluding that peptide released by the tumor is a precursor molecule. In agreement with these data, at variance with samples of normal dog gastric wall, IGF-II immunostaining was positive and in situ hybridization evidenced the expression of IGF-II mRNA in tumor tissue specimen. Evaluation of the molecular distribution of the IGFs in the circulation evidenced that IGF-II immunoreactivity was predominantly in the 3 5–65 kD region and barely detectable in the other regions. These results show that in dog, non-islet cell tumor hypoglycemia, as demonstrated in humans, can be ascribed to overproduction of IGF-II circulating in a molecular form that can more easily cross the capillary wall, thus exerting its insulin-like effects on target tissues. Andrea Boari, Istituto di Clinica Medical Veterinaria di Bologna, Via Tolara di Sopra, 40064 Ozzano Emilia (BO), Italy

Sign in / Sign up

Export Citation Format

Share Document