IGF-I is required for normal embryonic growth in mice.

Powell-Braxton, Lyn; Hollingshead, P G; Warburton, Corinna; Dowd, Mary; Pitts-Meek, Sharon; Dalton, Dyana K.; Gillett, Nancy A.; Stewart, Timothy A.

doi:10.1101/gad.7.12b.2609

Cited by 722 publications

(489 citation statements)

References 35 publications

Supporting

Mentioning

469

Contrasting

Unclassified

Order By: Relevance

“…The principal actions of IGF-I concern the control of growth and organ size through mitotic and antiapoptotic effects, as well as stimulation of protein synthesis. Consistent with this function, severe growth deficiency has been noted in transgenic animals lacking IGF-I or the type 1 IGF-IR (IGF-I receptor) [3,4].…”

Section: Introductionmentioning

confidence: 82%

IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK

Starkman

Cravero

DelCarlo

et al. 2005

Biochemical Journal

159

161

View full text Add to dashboard Cite

The IGF-I (insulin-like growth factor-I) signalling pathway responsible for regulation of proteoglycan synthesis in chondrocytes has not been defined and is the focus of the present study. Chondrocytes isolated from normal human articular cartilage were stimulated with IGF-I in monolayer culture or in suspension in alginate. IGF-I activated members of both the PI3K (phosphoinositide 3-kinase) pathway and the ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) pathway. The PI3K inhibitors LY294002 and wortmannin blocked IGF-I-stimulated Akt phosphorylation without blocking ERK phosphorylation and this was associated with complete inhibition of proteoglycan synthesis. A decrease in IGF-I-stimulated proteoglycan synthesis was also observed upon inhibition of mTOR (mammalian target of rapamycin) and p70S6 kinase, both of which are downstream of Akt. The MEK (MAPK/ERK kinase) inhibitors PD98059 and U0126 blocked IGF-I-stimulated ERK phosphorylation but did not block the phosphorylation of Akt and did not decrease proteoglycan synthesis. Instead, in alginate- cultured chondrocytes, the MEK inhibitors increased IGF-I-stimulated proteoglycan synthesis when compared with cells treated with IGF-I alone. This is the first study to demonstrate that IGF-I stimulation of the PI3K signalling pathway is responsible for the ability of IGF-I to increase proteoglycan synthesis. Although IGF-I also activates the ERK/MAPK pathway, ERK activity is not required for proteoglycan synthesis and may serve as a negative regulator

show abstract

Section: Introductionmentioning

confidence: 82%

IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK

Starkman

Cravero

DelCarlo

et al. 2005

Biochemical Journal

159

161

View full text Add to dashboard Cite

show abstract

“…Specifically, the IGF-I-deficient heterozygotes were 10-20 % smaller in total body size and in the size of individual organs, although these organs were histologically normal. IGF-I-deficient homozygotes were dead at birth, their body weight was 60 % of their wildtype siblings, and their lungs were not inflated [17]. It is evident that in these animal models IGF-I plays a fundamental role in muscle maturation and in the development of muscle mass.…”

Section: Discussionmentioning

confidence: 99%

“…Transgenic mice overexpressing IGF-I have enhanced body growth with an increase in muscle mass [37]. In contrast, mice deficient in IGF-I are significantly smaller than their litter mates, have a severe muscular dystrophy, and most ( 95 %) die at birth [17]. Specifically, the IGF-I-deficient heterozygotes were 10-20 % smaller in total body size and in the size of individual organs, although these organs were histologically normal.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Insulin-like growth factor (IGF-I) induces myotube hypertrophy associated with an increase in anaerobic glycolysis in a clonal skeletal-muscle cell model

Semsarian

Sutrave

Richmond

et al. 1999

Biochemical Journal

View full text Add to dashboard Cite

Insulin-like growth factor-I (IGF-I) is an important autocrine/paracrine mediator of skeletal-muscle growth and development. To develop a definitive cultured cell model of skeletal-muscle hypertrophy, C2C12 cells were stably transfected with IGF-I and clonal lines developed and evaluated. Quantitative morphometric analysis showed that IGF-I-transfected myotubes had a larger area (2381±60 µm2 versus 1429±39 µm2; P< 0.0001) and a greater maximum width (21.4±0.6 µm versus 13.9±0.3 µm; P< 0.0001) than control C2C12 myotubes, independent of the number of cell nuclei per myotube. IGF-I-transfected myotubes had higher levels of protein synthesis but no difference in DNA synthesis when compared with control myotubes, indicating the development of hypertrophy rather than hyperplasia. Both lactate dehydrogenase and alanine aminotransferase activities were increased (3- and 5-fold respectively), and total lactate levels were higher (2.3-fold) in IGF-I-transfected compared with control myotubes, indicating an increase in anaerobic glycolysis in the hypertrophied myotubes. However, expression of genes involved in skeletal-muscle growth or hypertrophy in vivo, e.g. myocyte nuclear factor and myostatin, was not altered in the IGF-I myotubes. Finally, myotube hypertrophy could also be induced by treatment of C2C12 cells with recombinant IGF-I or by growing C2C12 cells in conditioned media from IGF-I-transfected cells. This quantitative model should be uniquely useful for elucidating the molecular mechanisms of skeletal-muscle hypertrophy.

show abstract

“…Rare mutations in the human IGF1 gene lead to severe growth inhibition and mental retardation [11]. Igf1-null mice are born at 60% of normal birth weight, and the few that survive to adulthood are less than one-third the size of normal mice [12,13]. On the other hand, IGF2 is virtually dispensable for post-natal development in mice, since Igf2 expression is almost entirely limited to the embryo in rodents [14].…”

Section: Introductionmentioning

confidence: 99%

IGF2: Epigenetic regulation and role in development and disease

Chao

D'Amore

2008

Cytokine & Growth Factor Reviews

281

221

View full text Add to dashboard Cite

Insulin-like growth factor II (IGF2) is perhaps the most intricately regulated of all growth factors characterized to date. Its gene is imprinted-only one allele is active, depending on parental origin -and this pattern of expression is maintained epigenetically in almost all tissues. IGF2 activity is further controlled through differential expression of receptors and IGF-binding proteins (IGFBPs) that determine protein availability. This complex and multifaceted regulation emphasizes the importance of accurate IGF2 expression and activity. This review will examine the regulation of the IGF2 gene and what it has revealed about the phenomenon of imprinting, which is frequently disrupted in cancer. IGF2 protein function will be discussed, along with diseases that involve IGF2 overexpression. Roles for IGF2 in sonic hedgehog (Shh) signaling and angiogenesis will also be explored.

show abstract

IGF-I is required for normal embryonic growth in mice.

Cited by 722 publications

References 35 publications

IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK

IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK

Insulin-like growth factor (IGF-I) induces myotube hypertrophy associated with an increase in anaerobic glycolysis in a clonal skeletal-muscle cell model

IGF2: Epigenetic regulation and role in development and disease

Contact Info

Product

Resources

About