Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice

Sjögren, Klara; Liu, Jun Li; Blad, K.; Skrtic, Stanko; Vidal, Olle; Wallenius, Ville; LeRoith, Derek; Törnell, Jan; Isaksson, Olle; Jansson, John‐Olov; Ohlsson, Claes

doi:10.1073/pnas.96.12.7088

Cited by 832 publications

(667 citation statements)

References 36 publications

Supporting

Mentioning

608

Contrasting

Unclassified

Order By: Relevance

“…We had previously failed to correct angiotensin II induced muscle loss by infusing IGF-1 [15]. These findings suggested that autocrine effects of IGF-1 predominated in this model and were consistent with the demonstration that a liver-specific null mutation for IGF-1 failed to retard muscle growth [56]. Overexpression of IGF-1 in skeletal muscle (MLC/migf-1 mice), however, effectively blocked angiotensin II-induced muscle loss, strongly suggesting that depression of skeletal muscle IGF-1 played a causal role in angiotensin II-induced muscle loss [23 •• ].…”

Section: Insulin-like Growth Factor-1 Angiotensin II and Atrophysupporting

confidence: 69%

Angiotensin II as candidate of cardiac cachexia

Delafontaine

Akao

2006

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

View full text Add to dashboard Cite

Purpose of review-Congestive heart failure is increasing in prevalence and represents a major public health problem. The syndrome of advanced heart failure often includes muscle wasting, commonly termed cardiac cachexia, which is a predictor of poor outcome. Mechanisms of cardiac cachexia are poorly understood, but there is recent evidence that increased angiotensin II, interacting with the insulin-like growth factor-1 system, plays an important role.Recent findings-In animals, angiotensin II produces weight loss through a pressorindependent mechanism, accompanied by decreased levels of circulating and skeletal muscle insulin-like growth factor-1 and increased mRNA levels of the ubiquitin ligases atrogin-1 and Muscle RING finger-1 in skeletal muscle. Reduced insulin-like growth factor-1 action in muscle leads to increased proteolysis, through the ubiquitin-proteasome pathway, and increased apoptosis. These changes are blocked by muscle-specific expression of insulin-like growth factor-1, likely to be via the Akt/mTOR/p70S6K signaling pathway.Summary-The link between insulin-like growth factor-1, the ubiquitin-proteasome pathway, and angiotensin II effects has widespread clinical implications for the understanding of mechanisms of catabolic conditions. Therapeutic interventions targeting cross-talk mechanisms between angiotensin II and insulin-like growth factor-1 effects could provide new approaches for the treatment of muscle wasting.

show abstract

Section: Insulin-like Growth Factor-1 Angiotensin II and Atrophysupporting

confidence: 69%

Angiotensin II as candidate of cardiac cachexia

Delafontaine

Akao

2006

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

View full text Add to dashboard Cite

show abstract

“…Lack of liver IGF-I results in a 60% decrease of serum IGF-I levels, whereas in the rest of the body, including the brain, serum IGF-I levels are normal (11). Mice that are deficient in serum IGF-I do not exhibit developmental defects, probably because the levels of IGF-I in serum start to decline when development is already completed (11,12). Lox ϩ/ϩ Cre Ϫ littermates were used as controls.…”

Section: Methodsmentioning

confidence: 99%

Insulin-like growth factor I is required for vessel remodeling in the adult brain

López-López

LeRoith

Torres‐Alemán

2004

Proc. Natl. Acad. Sci. U.S.A.

348

274

View full text Add to dashboard Cite

Although vascular dysfunction is a major suspect in the etiology of several important neurodegenerative diseases, the signals involved in vessel homeostasis in the brain are still poorly understood. We have determined whether insulin-like growth factor I (IGF-I), a wide-spectrum growth factor with angiogenic actions, participates in vascular remodeling in the adult brain. IGF-I induces the growth of cultured brain endothelial cells through hypoxiainducible factor 1␣ and vascular endothelial growth factor, a canonical angiogenic pathway. Furthermore, the systemic injection of IGF-I in adult mice increases brain vessel density. Physical exercise that stimulates widespread brain vessel growth in normal mice fails to do so in mice with low serum IGF-I. Brain injury that stimulates angiogenesis at the injury site also requires IGF-I to promote perilesion vessel growth, because blockade of IGF-I input by an anti-IGF-I abrogates vascular growth at the injury site. Thus, IGF-I participates in vessel remodeling in the adult brain. Low serum͞brain IGF-I levels that are associated with old age and with several neurodegenerative diseases may be related to an increased risk of vascular dysfunction.

show abstract

“…(1)(2)(3)(4) Mouse models with liver-specific IGF-1 inactivation demonstrate that a major part (75% to 80%) of serum IGF-1 is liver-derived. (5,6) However, IGF-1 is also expressed locally in bone. (2,3) Thus there are two main sources of IGF-1 with a possible impact on the skeleton.…”

Section: Introductionmentioning

confidence: 99%

Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study

Ohlsson

Mellström

Carlzon

et al. 2010

Journal of Bone and Mineral Research

Self Cite

View full text Add to dashboard Cite

Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Insulin-like growth factor 1 (IGF-1) is a key determinant of bone mass, but the association between serum IGF-1 and incident fractures in men remains unclear. To determine the predictive value of serum IGF-1 for fracture risk in men, older men (n ¼ 2902, mean age of 75 years) participating in the prospective, population-based Osteoporotic Fractures in Men (MrOS) Sweden study were followed for a mean of 3.3 years. Serum IGF-1 was measured at baseline by radioimmunoassay. Fractures occurring after the baseline visit were validated. In age-adjusted hazards regression analyses, serum IGF-1 associated inversely with risk of all fractures [hazard ratio (HR) per SD decrease ¼ 1.23, 95% confidence interval (CI) 1.07-1.41], hip fractures (HR per SD decrease ¼ 1.45, 95% CI 1.07-1.97), and clinical vertebral fractures (HR per SD decrease ¼ 1.40, 95% CI 1.10-1-78). The predictive role of serum IGF-1 for fracture risk was unaffected by adjustment for height, weight, prevalent fractures, falls, and major prevalent diseases. Further adjustment for bone mineral density (BMD) resulted in an attenuated but still significant association between serum IGF-1 and fracture risk. Serum IGF-1 below but not above the median was inversely related to fracture incidence. The population-attributable risk proportion was 7.5% for all fractures and 22.9% for hip fractures. Taken together, older men with low serum IGF-1 have an increased fracture risk, especially for the two most important fracture types, hip and vertebral fractures. The association between serum IGF-1 and fracture risk is partly mediated via BMD. ß

show abstract

Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice

Cited by 832 publications

References 36 publications

Angiotensin II as candidate of cardiac cachexia

Angiotensin II as candidate of cardiac cachexia

Insulin-like growth factor I is required for vessel remodeling in the adult brain

Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study

Contact Info

Product

Resources

About