The Somatomedin Hypothesis: 2001
TLDR
In the liverspecific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF- I levels are normal.Abstract:
Since the original somatomedin hypothesis was conceived, a number of important discoveries have allowed investigators to modify the concept. Originally somatic growth was thought to be controlled by pituitary GH and mediated by circulating insulin-like growth factor-I (IGF-I, somatomedin C) expressed exclusively by the liver. With the discovery that IGF-I is produced by most, if not all, tissues, the role of autocrine/paracrine IGF-I vs. the circulating form has been hotly debated. Recent experiments using transgenic and gene-deletion technologies have attempted to answer these questions. In the liverspecific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF-I levels are normal. Thus, the normal postnatal growth and development in these animals may be due to normal free IGF-I levels (from as yet unidentified sources), although the role of autocrine/paracrine IGF-I has yet to be determined.read more
Citations
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Systemic complications of acromegaly: epidemiology, pathogenesis, and management.
TL;DR: The most important cause of morbidity and functional disability of this disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.
Journal ArticleDOI
Circulating levels of IGF-1 directly regulate bone growth and density
Shoshana Yakar,Clifford J. Rosen,Wesley G. Beamer,Cheryl L. Ackert-Bicknell,Yiping Wu,Jun-Li Liu,Guck T. Ooi,Jennifer Setser,Jan Frystyk,Yves R. Boisclair,Derek LeRoith +10 more
TL;DR: The double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF- 1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis.
Journal ArticleDOI
Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects.
TL;DR: The ability of GH to induce insulin resistance is significant for the defense against hypoglycemia, for the development of "stress" diabetes during fasting and inflammatory illness, and perhaps for the "Dawn" phenomenon (the increase in insulin requirements in the early morning hours).
Book ChapterDOI
Insulin-like growth factor signaling in fish.
TL;DR: The emergence of the zebrafish as a preferred model for development genetics has spawned progress in determining the requirements for IGF signaling during vertebrate embryonic development, and this review is intended as a summary of that progress.
Journal ArticleDOI
Calorie Restriction, Aging, and Cancer Prevention: Mechanisms of Action and Applicability to Humans*
TL;DR: This review synthesizes the key biological mechanisms underlying many of the beneficial effects of CR, with a particular focus on the insulin-like growth factor-1 pathway and some of the opportunities now available for investigations.
References
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Journal ArticleDOI
Ghrelin is a growth-hormone-releasing acylated peptide from stomach.
TL;DR: The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelIn, a peptide specifically releases GH both in vivo and in vitro.
Journal ArticleDOI
The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus.
Journal ArticleDOI
Insulin-Like Growth Factors and Their Binding Proteins: Biological Actions*
J. I. Jones,David R. Clemmons +1 more
TL;DR: In recognition of its generalized pleiotypic actions, sulfation factor was renamed somatomedin (mediator of the effects of somatotropin) and was included in the emerging classification of broad spectrum growth factors along with platelet derived growth factor, fibroblast growth factors, and epidermal growth factor.
Journal ArticleDOI
Hypothalamic Polypeptide That Inhibits the Secretion of Immunoreactive Pituitary Growth Hormone
Paul Brazeau,Wylie Vale,Roger Burgus,Nicholas Ling,Madalyn Butcher,Jean Rivier,Roger Guillemin +6 more
TL;DR: A peptide has been isolated from ovine hypothalamus which, at 1 x 10-9M, inhibits secretion in vitro of immunoreactive rat or human growth hormones and is similarly active in vivo in rats.
Journal ArticleDOI
Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r)
Jeh-Ping Liu,Julie C. Baker,Archlbald S. Perkins,Elizabeth J. Robertson,Argiris Efstratiadis +4 more
TL;DR: In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays in ossification, deviations from normalcy were observed in the central nervous system and epidermis.
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