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Cells Jan 2022Over the past two decades, interest in the role of the somatotroph growth hormone/insulin-like growth factor (GH/IGF1) axis in multiple aspects of physiology and...
Over the past two decades, interest in the role of the somatotroph growth hormone/insulin-like growth factor (GH/IGF1) axis in multiple aspects of physiology and pathology has grown exponentially [...].
Topics: Aging; Animals; Genomics; Growth Hormone; Humans; Signal Transduction; Somatomedins
PubMed: 35053333
DOI: 10.3390/cells11020217 -
Hormone Research in Paediatrics 2022The growth hormone (GH)-insulin-like growth factor (IGF) cascade is central to the regulation of growth and metabolism. This article focuses on the history of the... (Review)
Review
The growth hormone (GH)-insulin-like growth factor (IGF) cascade is central to the regulation of growth and metabolism. This article focuses on the history of the components of the IGF system, with an emphasis on the peptide hormones, IGF-I and -II, their cell surface receptors, and the IGF binding proteins (IGFBPs) and IGFBP proteases that regulate the availability of the peptide hormones for interaction with their receptors in relevant target tissues. We describe landmark events in the evolution of the somatomedin hypothesis, including evidence that has become available from experiments at the molecular and cellular levels, whole animal and tissue-specific gene knockouts, studies of cancer epidemiology, identification of prismatic human cases, and short- and long-term clinical trials of IGF-I therapy in humans. In addition, this new evidence has expanded our clinical definition of GH insensitivity (GHI) beyond growth hormone receptor mutations (classic Laron syndrome) to include conditions that cause primary IGF deficiency by impacting post-receptor signal transduction, IGF production, IGF availability to interact with the IGF-I receptor (IGF-1R), and defects in the IGF-1R, itself. We also discuss the clinical aspects of IGFs, from their description as insulin-like activity, to the use of IGF-I in the diagnosis and treatment of GH deficiency, and to the use of recombinant human IGF-I for therapy of children with GHI.
Topics: Animals; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Peptide Hormones; Protein Processing, Post-Translational; Signal Transduction; Somatomedins; Insulin-Like Growth Factor II
PubMed: 36446332
DOI: 10.1159/000527123 -
Journal of Dairy Science Aug 1993The neuroendocrine and immune systems participate as active partners in host homeostatic and defense mechanisms. This partnership involves a complex intercommunication... (Review)
Review
The neuroendocrine and immune systems participate as active partners in host homeostatic and defense mechanisms. This partnership involves a complex intercommunication system employing an array of shared ligands and receptors. Hormones of the somatolactogen family have marked influences on immune events in vivo, including the maintenance of lymphoid tissue cellularity, the promotion of DNA synthesis in these tissues, and the stimulation of a number of immune effector mechanisms. Both growth hormone and prolactin function to promote erythropoiesis and DNA synthesis in bone marrow precursors. Our results have shown that the somatolactogens and a member of the somatomedin family, IGF-I, are particularly effective in modulating the effector functions in phagocytic cells, including the production of reactive oxygen intermediates and tumor necrosis factor-alpha and the oxygen-dependent killing of bacteria. Evidence indicating a role of IGF-I in modulating immune functions is more recent but nonetheless compelling. Accumulated data suggest that somatolactogenic hormones, as well as one member of the somatomedins, are produced by cells of the immune system and can regulate local immune events. Although the molecular mechanisms by which the somatolactogens and somatomedins exert their effects on immune tissues are only now being explored, the pleiotropic nature of these effects suggests that these hormones participate at endocrine, paracrine, and perhaps autocrine sites of action.
Topics: Animals; Growth Hormone; Hematopoiesis; Insulin-Like Growth Factor I; Lymphocytes; Phagocytes; Placental Lactogen; Prolactin; Somatomedins
PubMed: 8408873
DOI: 10.3168/jds.S0022-0302(93)77579-7 -
Journal of Molecular Endocrinology Jul 2018The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily... (Review)
Review
The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily among endocrinologists who study growth and metabolism. The advancement of molecular endocrinology over the past four decades enables investigators to re-examine and refine the established somatomedin hypothesis. Specifically, gene deletions, transgene overexpression or more recently, cell-specific gene-ablations, have enabled investigators to study the effects of the and genes in temporal and spatial manners. The GH/IGF axis, acting in an endocrine and autocrine/paracrine fashion, is the major axis controlling skeletal growth. Studies in rodents have clearly shown that IGFs regulate bone length of the appendicular skeleton evidenced by changes in chondrocytes of the proliferative and hypertrophic zones of the growth plate. IGFs affect radial bone growth and regulate cortical and trabecular bone properties via their effects on osteoblast, osteocyte and osteoclast function. Interactions of the IGFs with sex steroid hormones and the parathyroid hormone demonstrate the significance and complexity of the IGF axis in the skeleton. Finally, IGFs have been implicated in skeletal aging. Decreases in serum IGFs during aging have been correlated with reductions in bone mineral density and increased fracture risk. This review highlights many of the most relevant studies in the IGF research landscape, focusing in particular on IGFs effects on the skeleton.
Topics: Animals; Chondrocytes; Humans; Osteoblasts; Osteoclasts; Skeleton; Somatomedins
PubMed: 29626053
DOI: 10.1530/JME-17-0298 -
Biochimica Et Biophysica Acta.... Nov 2019The insulin/insulin-like growth factor system (IIGFs) plays a fundamental role in the regulation of prenatal and postnatal growth, metabolism and homeostasis. As a... (Review)
Review
The insulin/insulin-like growth factor system (IIGFs) plays a fundamental role in the regulation of prenatal and postnatal growth, metabolism and homeostasis. As a consequence, dysregulation of this axis is associated with growth disturbance, type 2 diabetes, chronic inflammation and tumor progression. A functional crosstalk between IIGFs and discoidin domain receptors (DDRs) has been recently discovered. DDRs are non-integrin collagen receptors that canonically undergo slow and long-lasting autophosphorylation after binding to fibrillar collagen. While both DDR1 and DDR2 functionally interact with IIGFs, the crosstalk with DDR1 is so far better characterized. Notably, the IIGFs-DDR1 crosstalk presents a feed-forward mechanism, which does not require collagen binding, thus identifying novel non-canonical action of DDR1. Further studies are needed to fully explore the role of this IIGFs-DDRs functional loop as potential target in the treatment of inflammatory and neoplastic disorders.
Topics: Animals; Diabetes Mellitus, Type 2; Discoidin Domain Receptor 1; Discoidin Domain Receptor 2; Discoidin Domain Receptors; Fibrosis; Humans; Inflammation; Insulin; Insulin-Like Growth Factor II; Neoplasms; Phosphorylation; Protein Binding; Protein Isoforms; Receptor, Insulin; Receptors, Somatomedin; Signal Transduction; Somatomedins; Thyroid Neoplasms
PubMed: 31394114
DOI: 10.1016/j.bbamcr.2019.118522 -
Oncogene Jun 2022The insulin-like growth factors (IGFs) and their regulatory proteins-IGF receptors and binding proteins-are strongly implicated in cancer progression and modulate cell... (Review)
Review
The insulin-like growth factors (IGFs) and their regulatory proteins-IGF receptors and binding proteins-are strongly implicated in cancer progression and modulate cell survival and proliferation, migration, angiogenesis and metastasis. By regulating the bioavailability of the type-1 IGF receptor (IGF1R) ligands, IGF-1 and IGF-2, the IGF binding proteins (IGFBP-1 to -6) play essential roles in cancer progression. IGFBPs also influence cell communications through pathways that are independent of IGF1R activation. Noncoding RNAs (ncRNAs), which encompass a variety of RNA types including microRNAs (miRNAs) and long-noncoding RNAs (lncRNAs), have roles in multiple oncogenic pathways, but their many points of intersection with IGF axis functions remain to be fully explored. This review examines the functional interactions of miRNAs and lncRNAs with IGFs and their binding proteins in cancer, and reveals how the IGF axis may mediate ncRNA actions that promote or suppress cancer. A better understanding of the links between ncRNA and IGF pathways may suggest new avenues for prognosis and therapeutic intervention in cancer. Further, by exploring examples of intersecting ncRNA-IGF pathways in non-cancer conditions, it is proposed that new opportunities for future discovery in cancer control may be generated.
Topics: Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; MicroRNAs; Neoplasms; RNA, Long Noncoding; RNA, Untranslated; Receptors, Somatomedin
PubMed: 35597813
DOI: 10.1038/s41388-022-02353-3 -
Journal of Cellular and Molecular... Aug 2016Cardiovascular disease (CVD) constitutes a major public health threat worldwide, accounting for 17.3 million deaths annually. Heart disease and stroke account for the... (Review)
Review
Cardiovascular disease (CVD) constitutes a major public health threat worldwide, accounting for 17.3 million deaths annually. Heart disease and stroke account for the majority of healthcare costs in the developed world. While much has been accomplished in understanding the pathophysiology, molecular biology and genetics underlying the diagnosis and treatment of CVD, we know less about the role of epigenetics and their molecular determinants. The impact of environmental changes and epigenetics in CVD is now emerging as critically important in understanding the origin of disease and the development of new therapeutic approaches to prevention and treatment. This review focuses on the emerging role of epigenetics mediated by insulin like-growth factors-I and -II in major CVDs such as heart failure, cardiac hypertrophy and diabetes.
Topics: Animals; Cardiovascular Diseases; Epigenesis, Genetic; Humans; Models, Biological; Nutritional Physiological Phenomena; Somatomedins
PubMed: 27061217
DOI: 10.1111/jcmm.12845 -
International Journal of Molecular... Sep 2013Insulin system including ligands (insulin and IGFs) and their shared receptors (IR and IGFR) are critical regulators of insulin signaling and glucose homeostasis.... (Review)
Review
Insulin system including ligands (insulin and IGFs) and their shared receptors (IR and IGFR) are critical regulators of insulin signaling and glucose homeostasis. Altered insulin system is associated with major pathological conditions like diabetes and cancer. The mRNAs encoding for these ligands and their receptors are posttranscriptionally controlled by three major groups of regulators; (i) alternative splicing regulatory factors; (ii) turnover and translation regulator RNA-binding proteins (TTR-RBPs); and (iii) non-coding RNAs including miRNAs and long non-coding RNAs (lncRNAs). In this review, we discuss the influence of these regulators on alternative splicing, mRNA stability and translation. Due to the pathological impacts of insulin system, we also discussed the possibilities of discovering new potential regulators which will improve understanding of insulin system and associated diseases.
Topics: Alternative Splicing; Humans; Insulin; Ligands; Protein Processing, Post-Translational; RNA, Messenger; RNA, Untranslated; RNA-Binding Proteins; Receptor, Insulin; Receptors, Somatomedin; Somatomedins
PubMed: 24051403
DOI: 10.3390/ijms140919202 -
Nature Reviews. Endocrinology Mar 2015Neural stem cells (NSCs) are found in two regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus and the subventricular zone (SVZ)... (Review)
Review
Neural stem cells (NSCs) are found in two regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Similarly to other somatic stem cells, adult NSCs are found within specialized niches that are organized to facilitate NSC self-renewal. Alterations in stem-cell homeostasis can contribute to the consequences of neurodegenerative diseases, healthy ageing and tissue repair after damage. Insulin and the insulin-like growth factors (IGFs) function in stem-cell homeostasis across species. Studies in the mammalian central nervous system support essential roles for IGF and/or insulin signalling in NSC self-renewal, neurogenesis, cognition and sensory function through distinct ligand-receptor interactions. IGF-II is of particular interest as a result of its production by the choroid plexus and presence in cerebrospinal fluid (CSF). CSF regulates and supports the development, division and migration of cells in the adult brain and is required for NSC maintenance. In this Review, we discuss emerging data on the functions of IGF-II and IGF and/or insulin receptor signalling in the context of NSC regulation in the SVZ and SGZ. We also propose a model for IGF-II in which the choroid plexus is a major component of the NSC niche.
Topics: Animals; Brain; Cerebrospinal Fluid; Choroid Plexus; Dentate Gyrus; Homeostasis; Humans; Insulin; Lateral Ventricles; Mice; Models, Neurological; Neural Stem Cells; Neurogenesis; Neurons; Signal Transduction; Somatomedins
PubMed: 25445849
DOI: 10.1038/nrendo.2014.208 -
The Korean Journal of Gastroenterology... Jan 2012Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer.... (Review)
Review
Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.
Topics: Adipokines; Body Mass Index; Colorectal Neoplasms; Energy Intake; Exercise; Humans; Insulin Resistance; Meta-Analysis as Topic; Obesity; Somatomedins; Weight Loss
PubMed: 22289950
DOI: 10.4166/kjg.2012.59.1.16