Genomes and Genes
Gene Symbol: Igf1
Description: insulin-like growth factor 1
Alias: C730016P09Rik, Igf-1, Igf-I, insulin-like growth factor I, somatomedin
- Sanchez Calderon H, Rodriguez de la Rosa L, Milo M, Pichel J, Holley M, Varela Nieto I. RNA microarray analysis in prenatal mouse cochlea reveals novel IGF-I target genes: implication of MEF2 and FOXM1 transcription factors. PLoS ONE. 2010;5:e8699 pubmed publisher..Homozygous mutations of human IGF1 cause syndromic sensorineural deafness, decreased intrauterine and postnatal growth rates, and mental retardation...
- Elis S, Courtland H, Wu Y, Rosen C, Sun H, Jepsen K, et al. Elevated serum levels of IGF-1 are sufficient to establish normal body size and skeletal properties even in the absence of tissue IGF-1. J Bone Miner Res. 2010;25:1257-66 pubmed publisher..Overexpression of the rat igf1 transgene in livers of mice with otherwise normal IGF-1 expression (HIT mice) resulted in approximately threefold ..
- Scharin Tang M, Redfors B, Lindbom M, Svensson J, Ramunddal T, Ohlsson C, et al. Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling. Growth Horm IGF Res. 2012;22:206-11 pubmed publisher..These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. ..
- Santini M, Tsao L, Monassier L, Theodoropoulos C, Carter J, Lara Pezzi E, et al. Enhancing repair of the mammalian heart. Circ Res. 2007;100:1732-40 pubmed..The robust response achieved with the mIGF-1 isoform provides a mechanistic basis for clinically feasible therapeutic strategies for improving the outcome of heart disease. ..
- Elia L, Contu R, Quintavalle M, Varrone F, Chimenti C, Russo M, et al. Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions. Circulation. 2009;120:2377-85 pubmed publisher..Our results reveal a critical role of miR-1 in mediating the effects of the IGF-1 pathway and demonstrate a feedback loop between miR-1 expression and the IGF-1 signal transduction cascade. ..
- Yakar S, Rosen C, Bouxsein M, Sun H, Mejia W, Kawashima Y, et al. Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism. FASEB J. 2009;23:709-19 pubmed publisher..In summary, each IGF-1 complex constituent appears to play a distinct role in determining skeletal phenotype, with different effects on cortical and trabecular bone compartments. ..
- Svensson J, Tivesten A, Sjögren K, Isaksson O, Bergstrom G, Mohan S, et al. Liver-derived IGF-I regulates kidney size, sodium reabsorption, and renal IGF-II expression. J Endocrinol. 2007;193:359-66 pubmed..However, the LI-IGF-I(-/-) mice did not develop kidney failure or nephrosclerosis. One may speculate that liver-derived endocrine IGF-I induces renal IGF-II expression, resulting in symmetrical renal growth. ..
- Svensson J, Sjögren K, Fäldt J, Andersson N, Isaksson O, Jansson J, et al. Liver-derived IGF-I regulates mean life span in mice. PLoS ONE. 2011;6:e22640 pubmed publisher..Genes earlier reported to modulate stress response and collagen aging showed consistent regulation, providing mechanisms that could underlie the increased mean life span in the LI-IGF-I(-/-) mice. ..
- Kawai M, Delany A, Green C, Adamo M, Rosen C. Nocturnin suppresses igf1 expression in bone by targeting the 3' untranslated region of igf1 mRNA. Endocrinology. 2010;151:4861-70 pubmed publisherIGF-I is an anabolic factor that mediates GH and PTH actions in bone. Expression of skeletal Igf1 differs for inbred strains of mice, and Igf expression levels correlate directly with bone mass...
- Fritton J, Emerton K, Sun H, Kawashima Y, Mejia W, Wu Y, et al. Growth hormone protects against ovariectomy-induced bone loss in states of low circulating insulin-like growth factor (IGF-1). J Bone Miner Res. 2010;25:235-46 pubmed publisher..Interactions between estrogen and the GH/IGF-1 system as related to bone remodeling provide a pathway to minimize degeneration of bone tissue structure and osteoporotic fracture. ..
- Charalambous M, Ferron S, da Rocha S, Murray A, Rowland T, Ito M, et al. Imprinted gene dosage is critical for the transition to independent life. Cell Metab. 2012;15:209-21 pubmed publisher..This shows that appropriate dosage control at imprinted loci can act as a critical determinant in postnatal survival during phases of physiological adaptation. ..
- Cao J, Kurimoto P, Boudignon B, Rosen C, Lima F, Halloran B. Aging impairs IGF-I receptor activation and induces skeletal resistance to IGF-I. J Bone Miner Res. 2007;22:1271-9 pubmed
- Vendrame C, Carvalho M, Rios F, Manuli E, Petitto Assis F, Goto H. Effect of insulin-like growth factor-I on Leishmania amazonensis promastigote arginase activation and reciprocal inhibition of NOS2 pathway in macrophage in vitro. Scand J Immunol. 2007;66:287-96 pubmed
- Barton E, DeMeo J, Lei H. The insulin-like growth factor (IGF)-I E-peptides are required for isoform-specific gene expression and muscle hypertrophy after local IGF-I production. J Appl Physiol (1985). 2010;108:1069-76 pubmed publisher..The igf1 gene not only produces IGF-I, but also generates multiple carboxy-terminal extensions, the E-peptides, through ..
- Cannata D, Lann D, Wu Y, Elis S, Sun H, Yakar S, et al. Elevated circulating IGF-I promotes mammary gland development and proliferation. Endocrinology. 2010;151:5751-61 pubmed publisher..This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation. ..
- Lau K, Baylink D, Zhou X, Rodriguez D, Bonewald L, Li Z, et al. Osteocyte-derived insulin-like growth factor I is essential for determining bone mechanosensitivity. Am J Physiol Endocrinol Metab. 2013;305:E271-81 pubmed publisherThis study sought to determine whether deficient Igf1 expression in osteocytes would affect loading-induced osteogenic response...
- Temmerman L, Slonimsky E, Rosenthal N. Class 2 IGF-1 isoforms are dispensable for viability, growth and maintenance of IGF-1 serum levels. Growth Horm IGF Res. 2010;20:255-63 pubmed publisher..We also uncover a vital requirement of IGF-1 for perinatal viability, previously obscured by modifiers in heterogeneous genetic backgrounds. ..
- Iresjö B, Svensson J, Ohlsson C, Lundholm K. Liver-derived endocrine IGF-I is not critical for activation of skeletal muscle protein synthesis following oral feeding. BMC Physiol. 2013;13:7 pubmed publisher..05), but less so in IGF-I (-/-) knockouts (p?<?0.08). This study demonstrates that re-synthesis of muscle proteins following starvation is not critically dependent on endocrine liver-derived IGF-I. ..
- Sunters A, Armstrong V, Zaman G, Kypta R, Kawano Y, Lanyon L, et al. Mechano-transduction in osteoblastic cells involves strain-regulated estrogen receptor alpha-mediated control of insulin-like growth factor (IGF) I receptor sensitivity to Ambient IGF, leading to phosphatidylinositol 3-kinase/AKT-dependent Wnt/LRP5 r. J Biol Chem. 2010;285:8743-58 pubmed publisher..This cascade requires prostanoid/nitric oxide production and is independent of Wnt/LRP5. ..
- Zhu L, Pollard J. Estradiol-17beta regulates mouse uterine epithelial cell proliferation through insulin-like growth factor 1 signaling. Proc Natl Acad Sci U S A. 2007;104:15847-51 pubmed..Once the IGF1 pathway is activated, inhibition of ER signaling demonstrates that it is independent of ER...
- Wu Y, Sun H, Yakar S, LeRoith D. Elevated levels of insulin-like growth factor (IGF)-I in serum rescue the severe growth retardation of IGF-I null mice. Endocrinology. 2009;150:4395-403 pubmed publisher..Furthermore, we show that tissue IGF-I is necessary for the development of the female reproductive system and cannot be compensated by elevated levels of serum IGF-I. ..
- Llorens Martín M, Torres Aleman I, Trejo J. Exercise modulates insulin-like growth factor 1-dependent and -independent effects on adult hippocampal neurogenesis and behaviour. Mol Cell Neurosci. 2010;44:109-17 pubmed publisher..The short-term anxiolytic-like effect of exercise was IGF1-dependent and indeed, the recall of hippocampus-dependent spatial memory is impaired by blocking serum IGF1 (as ..
- Shai S, Sukhanov S, Higashi Y, Vaughn C, Rosen C, Delafontaine P. Low circulating insulin-like growth factor I increases atherosclerosis in ApoE-deficient mice. Am J Physiol Heart Circ Physiol. 2011;300:H1898-906 pubmed publisher..Our data establish a link between lower circulating IGF-I and increased atherosclerosis that has important clinical implications. ..
- Yakar S, Courtland H, Clemmons D. IGF-1 and bone: New discoveries from mouse models. J Bone Miner Res. 2010;25:2543-52 pubmed publisher..In this review we present new and old findings from mouse models of the IGF system and discuss their clinical relevance to normal and pathological skeletal physiology. ..
- Leduc M, Hageman R, Meng Q, Verdugo R, Tsaih S, Churchill G, et al. Identification of genetic determinants of IGF-1 levels and longevity among mouse inbred strains. Aging Cell. 2010;9:823-36 pubmed publisher..The most significant locus was the QTL on Chr 10, which contains the Igf1 gene and which had a LOD score of 31.8...
- Trejo J, Piriz J, Llorens Martin M, Fernandez A, Bolos M, LeRoith D, et al. Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects. Mol Psychiatry. 2007;12:1118-28 pubmed..Declining levels of serum IGF-I during aging may therefore contribute to age-associated cognitive loss. ..
- Bailey Downs L, Mitschelen M, Sosnowska D, Toth P, Pinto J, Ballabh P, et al. Liver-specific knockdown of IGF-1 decreases vascular oxidative stress resistance by impairing the Nrf2-dependent antioxidant response: a novel model of vascular aging. J Gerontol A Biol Sci Med Sci. 2012;67:313-29 pubmed publisher..in the vasculature, we utilized a novel mouse model with a liver-specific adeno-associated viral knockdown of the Igf1 gene using Cre-lox technology (Igf1(f/f) + MUP-iCre-AAV8), which exhibits a significant decrease in circulating IGF-..
- Sheng M, Zhou X, Bonewald L, Baylink D, Lau K. Disruption of the insulin-like growth factor-1 gene in osteocytes impairs developmental bone growth in mice. Bone. 2013;52:133-44 pubmed publisher..insulin-like growth factor 1 (IGF-1) in developmental bone growth by assessing the bone phenotype of osteocyte Igf1 conditional knockout (KO) mice, generated by crossing the Dmp1-driven Cre-expressing transgenic mice with Igf1 ..
- Csiszar A, Labinskyy N, Perez V, Recchia F, Podlutsky A, Mukhopadhyay P, et al. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol Heart Circ Physiol. 2008;295:H1882-94 pubmed publisher..Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress. ..
- Govoni K, Wergedal J, Florin L, Angel P, Baylink D, Mohan S. Conditional deletion of insulin-like growth factor-I in collagen type 1alpha2-expressing cells results in postnatal lethality and a dramatic reduction in bone accretion. Endocrinology. 2007;148:5706-15 pubmed..In conclusion, both local and endocrine IGF-I actions are involved in regulating growth of various tissues including bone, but they act via different mechanisms. ..
- Johannesson B, Sattler S, Semenova E, Pastore S, Kennedy Lydon T, Sampson R, et al. Insulin-like growth factor-1 induces regulatory T cell-mediated suppression of allergic contact dermatitis in mice. Dis Model Mech. 2014;7:977-85 pubmed publisher..Similar therapeutic effects can be achieved with systemic or topical delivery of IGF-1, implicating this growth factor as a promising new therapeutic option for the treatment of ACD. ..
- Courtland H, DeMambro V, Maynard J, Sun H, Elis S, Rosen C, et al. Sex-specific regulation of body size and bone slenderness by the acid labile subunit. J Bone Miner Res. 2010;25:2059-68 pubmed publisher..This study revealed age- and sex-specific dependencies of body size and bone size on the ALS. These findings may explain the heterogeneity in growth and BMD measurements reported in human ALS-deficient patients. ..
- Sukhanov S, Higashi Y, Shai S, Blackstock C, Galvez S, Vaughn C, et al. Differential requirement for nitric oxide in IGF-1-induced anti-apoptotic, anti-oxidant and anti-atherosclerotic effects. FEBS Lett. 2011;585:3065-72 pubmed publisher..Thus IGF-1's anti-oxidant effect is dependent on its ability to increase NO but is distinct from its anti-atherosclerotic effect which is NO-independent. ..
- Pfeffer L, Brisson B, Lei H, Barton E. The insulin-like growth factor (IGF)-I E-peptides modulate cell entry of the mature IGF-I protein. Mol Biol Cell. 2009;20:3810-7 pubmed publisher..Insulin-like growth factor (IGF)-I is a critical protein for cell development and growth. Alternative splicing of the igf1 gene gives rise to multiple isoforms...
- Rodriguez de la Rosa L, Fernandez Sanchez L, Germain F, Murillo Cuesta S, Varela Nieto I, de la Villa P, et al. Age-related functional and structural retinal modifications in the Igf1-/- null mouse. Neurobiol Dis. 2012;46:476-85 pubmed publisher..role of IGF-I in retinal physiology, we have studied the morphology and electrophysiology of the retina of the Igf1(-/-) mice in comparison with that of the Igf1(+/-) and Igf1(+/+) animals during aging...
- Yuan R, Tsaih S, Petkova S, Marin de Evsikova C, Xing S, Marion M, et al. Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels. Aging Cell. 2009;8:277-87 pubmed publisher..is the initial paper of a series, the study design, median lifespans, and circulating insulin-like growth factor 1 (IGF1) levels at 6, 12, and 18 months are described for the first cohort of 32 females and 32 males of each strain...
- Hewitt S, Li Y, Li L, Korach K. Estrogen-mediated regulation of Igf1 transcription and uterine growth involves direct binding of estrogen receptor alpha to estrogen-responsive elements. J Biol Chem. 2010;285:2676-85 pubmed publisherEstrogen enables uterine proliferation, which depends on synthesis of the IGF1 growth factor...
- Okano T, Xuan S, Kelley M. Insulin-like growth factor signaling regulates the timing of sensory cell differentiation in the mouse cochlea. J Neurosci. 2011;31:18104-18 pubmed publisher..The results also provide new insights regarding the pathological processes that underlie auditory defects in the absence of IGF signaling in both humans and mice. ..
- Shai S, Sukhanov S, Higashi Y, Vaughn C, Kelly J, Delafontaine P. Smooth muscle cell-specific insulin-like growth factor-1 overexpression in Apoe-/- mice does not alter atherosclerotic plaque burden but increases features of plaque stability. Arterioscler Thromb Vasc Biol. 2010;30:1916-24 pubmed publisher..These findings indicate that stimulation of VSMC IGF-1 signaling does not alter total atherosclerotic plaque burden and may improve atherosclerotic plaque stability. ..
- Günschmann C, Stachelscheid H, Akyuz M, Schmitz A, Missero C, Bruning J, et al. Insulin/IGF-1 controls epidermal morphogenesis via regulation of FoxO-mediated p63 inhibition. Dev Cell. 2013;26:176-87 pubmed publisher..Collectively, the present study reveals a critical role for IIS-dependent control of p63 activity in coordination of ACD and stratification during epithelial morphogenesis. ..
- Hede M, Salimova E, Piszczek A, Perlas E, Winn N, Nastasi T, et al. E-peptides control bioavailability of IGF-1. PLoS ONE. 2012;7:e51152 pubmed publisher..Thus, the E-peptides control IGF-1 bioavailability by preventing systemic circulation, offering a potentially powerful way to tether IGF-1 and other therapeutic proteins to the site of synthesis and/or administration. ..
- Imrie H, Abbas A, Viswambharan H, Rajwani A, Cubbon R, Gage M, et al. Vascular insulin-like growth factor-I resistance and diet-induced obesity. Endocrinology. 2009;150:4575-82 pubmed publisher..Vascular IGF-I resistance may represent a novel therapeutic target to prevent or slow the accelerated vasculopathy seen in humans with obesity or type 2 diabetes mellitus. ..
- Stratikopoulos E, Szabolcs M, Dragatsis I, Klinakis A, Efstratiadis A. The hormonal action of IGF1 in postnatal mouse growth. Proc Natl Acad Sci U S A. 2008;105:19378-83 pubmed publisherThe mammalian insulin-like growth factor 1 (IGF1), which is a member of a major growth-promoting signaling system, is produced by many tissues and functions throughout embryonic and postnatal development in an autocrine/paracrine fashion...
- Svensson J, Kindblom J, Shao R, Moverare Skrtic S, Lagerquist M, Andersson N, et al. Liver-derived IGF1 enhances the androgenic response in prostate. J Endocrinol. 2008;199:489-97 pubmed publisherBoth IGF1 and androgens are major enhancers of prostate growth and are implicated in the development of prostate hyperplasia and cancer...
- Colombini B, Benelli G, Nocella M, Musaro A, Cecchi G, Bagni M. Mechanical properties of intact single fibres from wild-type and MLC/mIgf-1 transgenic mouse muscle. J Muscle Res Cell Motil. 2009;30:199-207 pubmed publisher..In contrast to the other parameters, static stiffness in TG fibres was about 24% smaller than in WT fibres suggesting a possible effect of Igf-1 overexpression on its mechanism. ..
- Govoni K, Lee S, Chung Y, Behringer R, Wergedal J, Baylink D, et al. Disruption of insulin-like growth factor-I expression in type IIalphaI collagen-expressing cells reduces bone length and width in mice. Physiol Genomics. 2007;30:354-62 pubmed..20). In conclusion, IGF-I from cells expressing procollagen type IIalphaI regulates bone accretion that occurs during postnatal growth period. ..
- von der Thüsen J, Borensztajn K, Moimas S, van Heiningen S, Teeling P, Van Berkel T, et al. IGF-1 has plaque-stabilizing effects in atherosclerosis by altering vascular smooth muscle cell phenotype. Am J Pathol. 2011;178:924-34 pubmed publisher..We believe that IGF-1 in atherosclerotic plaques may have a role in preventing plaque instability, not only by modulating smooth muscle cell turnover, but also by altering smooth muscle cell phenotype. ..
- Galvin C, Hardiman O, Nolan C. IGF-1 receptor mediates differentiation of primary cultures of mouse skeletal myoblasts. Mol Cell Endocrinol. 2003;200:19-29 pubmed
- Liao L, Dearth R, Zhou S, Britton O, Lee A, Xu J. Liver-specific overexpression of the insulin-like growth factor-I enhances somatic growth and partially prevents the effects of growth hormone deficiency. Endocrinology. 2006;147:3877-88 pubmed..Higher circulating levels of IGF-I can stimulate somatic growth and lean mass and improve glucose tolerance. ..
- Welch S, Plank D, Witt S, Glascock B, Schaefer E, Chimenti S, et al. Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice. Circ Res. 2002;90:641-8 pubmed
- Delahunty K, Shultz K, Gronowicz G, Koczon Jaremko B, Adamo M, Horton L, et al. Congenic mice provide in vivo evidence for a genetic locus that modulates serum insulin-like growth factor-I and bone acquisition. Endocrinology. 2006;147:3915-23 pubmed..3-Mb region containing approximately 148 genes, including Igf1 and Elk-3(ETS domain protein)...
- Kasukawa Y, Baylink D, Wergedal J, Amaar Y, Srivastava A, Guo R, et al. Lack of insulin-like growth factor I exaggerates the effect of calcium deficiency on bone accretion in mice. Endocrinology. 2003;144:4682-9 pubmed
- Miyakoshi N, Kasukawa Y, Linkhart T, Baylink D, Mohan S. Evidence that anabolic effects of PTH on bone require IGF-I in growing mice. Endocrinology. 2001;142:4349-56 pubmed..These data to our knowledge provide the first direct evidence that the anabolic effects of PTH on bone formation in vivo require IGF-I action in growing mice. ..
- Baker J, Liu J, Robertson E, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell. 1993;75:73-82 pubmed
- Liu J, Grinberg A, Westphal H, Sauer B, Accili D, Karas M, et al. Insulin-like growth factor-I affects perinatal lethality and postnatal development in a gene dosage-dependent manner: manipulation using the Cre/loxP system in transgenic mice. Mol Endocrinol. 1998;12:1452-62 pubmed..This variability allows for postnatal survival and will enable one to begin to explore the role of the endocrine vs. paracrine effects of IGF-I. ..
- Schmid C. Insulin-like growth factors. Cell Biol Int. 1995;19:445-57 pubmedThe insulin-like growth factors I and II are single chain polypeptides homologous to proinsulin. IGF I and IGF II contribute to cell regulation and stimulate protein synthesis via signaling through type 1 receptors which are homologous ..
- He J, Rosen C, Adams D, Kream B. Postnatal growth and bone mass in mice with IGF-I haploinsufficiency. Bone. 2006;38:826-35 pubmedWe examined the influence of IGF-I haploinsufficiency on growth, bone mass and osteoblast differentiation in Igf1 heterozygous knockout (HET) mice...
- Jiang J, Lichtler A, Gronowicz G, Adams D, Clark S, Rosen C, et al. Transgenic mice with osteoblast-targeted insulin-like growth factor-I show increased bone remodeling. Bone. 2006;39:494-504 pubmed..Thus, broad overexpression of IGF-I in cells of the osteoblast lineage increased indices of bone formation and resorption. ..
- Yakar S, Liu J, Fernandez A, Wu Y, Schally A, Frystyk J, et al. Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity. Diabetes. 2001;50:1110-8 pubmed..These data provide evidence of the role of circulating IGF-I as an important component of overall insulin action in peripheral tissues. ..
- Baker J, Hardy M, Zhou J, Bondy C, Lupu F, Bellve A, et al. Effects of an Igf1 gene null mutation on mouse reproduction. Mol Endocrinol. 1996;10:903-18 pubmedBoth sexes of adult mice homozygous for a targeted mutation of the Igf1 gene, encoding insulin-like growth factor 1, are infertile dwarfs (approximately 30% of normal size)...
- Ruan W, Kleinberg D. Insulin-like growth factor I is essential for terminal end bud formation and ductal morphogenesis during mammary development. Endocrinology. 1999;140:5075-81 pubmed..These results suggest that IGF-I, when given along with E2, is responsible for ductal morphogenesis. ..