scholarly journals Cooperation between Shh and IGF-I in promoting myogenic proliferation and differentiation via the MAPK/ERK and PI3K/Akt pathways requires smo activity

2012 ◽  
Vol 227 (4) ◽  
pp. 1455-1464 ◽  
Author(s):  
D. Madhala-Levy ◽  
V.C. Williams ◽  
S.M. Hughes ◽  
R. Reshef ◽  
O. Halevy
Keyword(s):  
Proliferation And Differentiation ◽  
Igf I

scholarly journals Insulin-like growth factor-I signaling is modified during chondrocyte differentiation

2004 ◽  
Vol 183 (3) ◽  
pp. 477-486 ◽  
Author(s):  
Chanika Phornphutkul ◽  
Ke-Ying Wu ◽  
Xu Yang ◽  
Qian Chen ◽  
Philip A Gruppuso
Keyword(s):  
Growth Factor ◽  
Cell Line ◽  
Chondrocyte Differentiation ◽  
Erk Pathway ◽  
Insulin Like Growth Factor ◽  
Erk Activation ◽  
Atdc5 Cell ◽  
Factor I ◽  
Proliferation And Differentiation ◽  
Igf I

Insulin-like growth factor-I (IGF-I) is a critical regulator of skeletal growth. While IGF-I has been shown to be a potent chondrocyte mitogen in vitro, its role in chondrocyte differentiation is less well characterized. We chose to study the action of IGF-I on an accepted model of chondrocyte differentiation, the ATDC5 cell line. Insulin concentrations sufficiently high to interact with the IGF-I receptor are routinely used to induce ATDC5 cells to differentiate. Therefore, we first examined the ability of IGF-I to promote chondrocyte differentiation at physiological concentrations. IGF-I could induce differentiation of these cells at concentrations below 10 nM. However, increasing IGF-I concentrations were less potent at inducing differentiation. We hypothesized that mitogenic effects of IGF-I might inhibit its differentiating effects. Indeed, the extracellular-signal-regulated kinase (ERK)-pathway inhibitor PD98059 inhibited ATDC5 cell DNA synthesis while enhancing differentiation. This suggested that the ability of IGF-I to promote both proliferation and differentiation might require that its signaling be modulated through the differentiation process. We therefore compared IGF-I-mediated ERK activation in proliferating and hypertrophic chondrocytes. IGF-I potently induced ERK activation in proliferating cells, but minimal ERK response was seen in hypertrophic cells. In contrast, IGF-I-mediated Akt activation was unchanged by differentiation, indicating intact upstream IGF-I receptor signaling. Similar findings were observed in the RCJ3.1C5.18 chondrogenic cell line and in primary chick chondrocytes. We conclude that IGF-I promotes both proliferation and differentiation of chondrocytes and that the differentiation effects of IGF-I may require uncoupling of signaling to the ERK pathway.

Influence of somatotropin on lipid metabolism and IGF gene expression in porcine adipose tissue

1992 ◽  
Vol 263 (4) ◽  
pp. E637-E645 ◽  
Author(s):  
C. K. Wolverton ◽  
M. J. Azain ◽  
J. Y. Duffy ◽  
M. E. White ◽  
T. G. Ramsay
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Dietary Fat ◽  
Subcutaneous Adipose Tissue ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Systemic Factors ◽  
Subcutaneous Adipose ◽  
Acid Esterification

The present study was designed to evaluate the effects of porcine somatotropin (pST) treatment (2 mg/day) and dietary fat (10%) separately and in combination on the metabolic activity of subcutaneous adipose tissue, serum adipogenic activity, and insulin-like growth factor (IGF) gene expression within adipose tissue from growing 5- to 6-mo-old barrows. This study attempted to determine how these factors might contribute to the reported changes in adiposity of treated swine. Biopsies of adipose tissue were collected after 28 days of treatment following anesthesia with thiopental sodium (15 mg/kg iv). Somatotropin inhibited in vitro glucose oxidation and lipogenesis in adipose tissue but did not affect fatty acid esterification. Adipogenic activity of serum was not altered by pST treatment. Subcutaneous adipose tissue contained mRNA for IGF-I and -II, and pST administration increased the abundance of IGF-I mRNA. Dietary fat had no effect on these variables. Thus somatotropin reduces glucose metabolism in porcine subcutaneous adipose tissue. Preadipocyte proliferation and differentiation are not affected by somatotropin through its actions on systemic factors. Dietary fat provides no additional benefit in combination with pST administration to affect accretion of adipose tissue in growing swine.

scholarly journals Loss of IGF-IEa or IGF-IEb Impairs Myogenic Differentiation

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1923-1934 ◽  
Author(s):  
Ronald W. Matheny ◽  
Bradley C. Nindl
Keyword(s):  
Splice Variants ◽  
Myogenic Differentiation ◽  
Horse Serum ◽  
Myoblast Differentiation ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Simultaneous Loss ◽  
Functional Relevance ◽  
Free Media ◽  
The Impact

Actions of protein products resulting from alternative splicing of the Igf1 gene have received increasing attention in recent years. However, the significance and functional relevance of these observations remain poorly defined. To address functions of IGF-I splice variants, we examined the impact of loss of IGF-IEa and IGF-IEb on the proliferation and differentiation of cultured mouse myoblasts. RNA interference-mediated reductions in total IGF-I, IGF-IEa alone, or IGF-IEb alone had no effect on cell viability in growth medium. However, cells deficient in total IGF-I or IGF-IEa alone proliferated significantly slower than control cells or cells deficient in IGF-IEb in serum-free media. Simultaneous loss of both or specific loss of either splice variant significantly inhibited myosin heavy chain (MyHC) immunoreactivity by 70–80% (P < 0.01) under differentiation conditions (48 h in 2% horse serum) as determined by Western immunoblotting. This loss in protein was associated with reduced MyHC isoform mRNAs, because reductions in total IGF-I or IGF-IEa mRNA significantly reduced MyHC mRNAs by approximately 50–75% (P < 0.05). Loss of IGF-IEb also reduced MyHC isoform mRNA significantly, with the exception of Myh7, but to a lesser degree (∼20–40%, P < 0.05). Provision of mature IGF-I, but not synthetic E peptides, restored Myh3 expression to control levels in cells deficient in IGF-IEa or IGF-IEb. Collectively, these data suggest that IGF-I splice variants may regulate myoblast differentiation through the actions of mature IGF-I and not the E peptides.

The negative effect of GH/IGF-1 excess on NAD- and NADP-dependent blood lymphocytes dehydrogenases activity in acromegaly

2016 ◽  
Vol 62 (5) ◽  
pp. 59-60
Author(s):  
Margarita A. Dudina ◽  
Sergey A. Dogadin ◽  
Аndrey A. Savchenko
Keyword(s):  
Tricarboxylic Acid Cycle ◽  
Blood Lymphocytes ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Negative Effect ◽  
Active Acromegaly ◽  
Dehydrogenases Activity ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Potent Effector

Background. Acromegaly is a rare serious condition characterized by chronic hypersecretion of growth hormone (GH) from a pituitary adenoma and induces the synthesis of insulin-like growth factor I (IGF-1). The idea of the crucial GH importance not only in the control of cell proliferation and differentiation, but, also, in the regulation of immune cells metabolism allows to think that chronic excess GH/IGF-I in acromegaly is the potent effector distortion of the immune response mechanisms. Aim. To study the NAD(P)-dependent dehydrogenases level in blood lymphocytes and their interaction with GH/IGF-1 concentration in patients with active acromegaly.Methods. The level of NAD(P)-dependent dehydrogenases in blood lymphocytes was studied in a group of 88 patients with active acromegaly, mean age 51.0±12.5 years. The NAD(P)-dependent dehydrogenases activity was determined by biochemiluminescence method. The concentrations of GH and IGF-1 were measured by ELISA.Results. Studying the activity of mitochondrial NAD(P)-dependent dehydrogenases found a decrease in all NAD-dependent oxidoreductase: NADIDH, NADGDH, and MDH (P<0.01), which allows to state the low level flow in the tricarboxylic acid cycle. In active acromegaly were revealed the decreasing activity of all studied oxidoreductases: glucose-6-phosphate dehydrogenase (P<0.01), NAD–lactate dehydrogenase (LDH) (P<0.001), NADH–LDH (P<0.001), NAD–malate dehydrogenase (MDH) (P<0.001), NADH–MDH (P<0.001), NADP–MDH (P<0.001), NAD–glutamate dehydrogenases (GDH) and NADH–GDH (P<0.001), NADP–GDH and NADPH–GDH (P<0.001), NAD–isocitrate dehydrogenases (IDH) and NADP–IDH (P<0.01 and P<0.001 respectively), and, also, glutathione reductase (P<0.001). Our data observed that decreasing activity of NADP–GDH positively correlated with the basal GH level (r=+0.23, P=0.04) and NADP–MDH activity with IGF-1 level (r=+0.30, P=0.008). The low NADH–MDH activity negatively correlated to the basal GH concentration (r=−0.23, P=0.04).Conclusion. The chronic excess of GH/IGF-1 causes a significant depletion of metabolic lymphocytes reserves and may play an important role in several systems malignancies of acromegaly patients. This pathway continues to attract interest as a potentially useful target for therapeutic design of acromegaly.

Changes in IGF-I and -II expression and secretion during the proliferation and differentiation of normal rat osteoblasts

1995 ◽  
Vol 144 (2) ◽  
pp. 251-259 ◽  
Author(s):  
R S Birnbaum ◽  
R R Bowsher ◽  
K M Wiren
Keyword(s):  
Extracellular Matrix ◽  
Physiological Role ◽  
Mrna Levels ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Igf Binding ◽  
Normal Rat ◽  
Osteoblast Development ◽  
Igf Binding Protein

Abstract IGF-I and -II have potent effects on proliferation and differentiation of osteoblasts in vitro. These cells secrete both IGFs and expression of these peptides is regulated by several of the hormones and growth factors that promote bone resorption and/or formation. However, the physiological role(s) of IGFs in the remodelling process of adult bone is still unclear. Some confusion may arise from results influenced, in part, by differences in the state of osteoblast development of in vitro cultures. Several laboratories have demonstrated that murine osteoblast cultures progress from proliferating preosteoblasts, to mature differentiated osteoblasts that form an extracellular matrix, to cultures that form a mineralized matrix. We have recently documented changes in IGF-binding protein expression and secretion in these cultures. To complement and extend this work, we have examined IGF-I expression and secretion and IGF-II expression during in vitro osteoblast development. Steady-state mRNA levels of both IGF-I and -II increased from the earliest time examined, day 5 in culture, to a maximum at day 11 and, thereafter, declined. IGF-I secreted into the medium also changed in a biphasic manner, but IGF-II could not be quantitated due to the sensitivity of our assay. Secretion of IGF-I was lowest between days 8 and 14. IGF-I secretion on day 5 was significantly greater than day 8. Similarly, IGF-I secretion from day 17 to 26 was also greater than observed for days 8 to 14. If differentiation of the cells was inhibited, this late rise in IGF-I secretion was abolished. We conclude that IGF-I is an autocrine mitogen of the proliferating preosteoblasts. Further, we also suggest that the rise in IGF-I secretion, late in osteoblast development, may lead to sequestration of this mitogen in the extracellular matrix for release during a subsequent remodelling cycle. Journal of Endocrinology (1995) 144, 251–259

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