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Diabetes Jun 2023
Topics: Hexosaminidase A; Liver; Somatomedins; Muscle, Skeletal; Glucose
PubMed: 37205863
DOI: 10.2337/dbi22-0040 -
Pediatric Endocrinology Reviews : PER Sep 2018The purpose of this review is to describe and document the discovery of growth hormone (GH) and various activities associated with it. Crucial to this discourse will be... (Review)
Review
The purpose of this review is to describe and document the discovery of growth hormone (GH) and various activities associated with it. Crucial to this discourse will be a chronicle of results related to the structure of GH. Many individuals were instrumental in the early and current work. Throughout the review we present glimpses into their scientific lives as it affects the evolution of GH's story. We realize that we have not presented a comprehensive review of GH's history and its current and future status, and apologize for the omission of many individuals who contributed to this story.
Topics: Growth Hormone; Humans; Insulin-Like Growth Factor I
PubMed: 30378777
DOI: 10.17458/per.vol16.2018.bbk.ghdiscoverystructure -
Cold Spring Harbor Perspectives in... Mar 2020Within the realm of zoological study, the question of how an organism reaches a specific size has been largely unexplored. Recently, studies performed to understand the... (Review)
Review
Within the realm of zoological study, the question of how an organism reaches a specific size has been largely unexplored. Recently, studies performed to understand the regulation of organ size have revealed that both cellular signals and external cues contribute toward the determination of total cell mass within each organ. The establishment of final organ size requires the precise coordination of cell growth, proliferation, and survival throughout development and postnatal life. In the mammalian heart, the regulation of size is biphasic. During development, cardiomyocyte proliferation predominantly determines cardiac growth, whereas in the adult heart, total cell mass is governed by signals that regulate cardiac hypertrophy. Here, we review the current state of knowledge regarding the extrinsic factors and intrinsic mechanisms that control heart size during development. We also discuss the metabolic switch that occurs in the heart after birth and precedes homeostatic control of postnatal heart size.
Topics: Animals; Cardiomegaly; Cell Cycle; Cell Proliferation; Cell Survival; Heart; Humans; Hypertrophy; Myocardium; Myocytes, Cardiac; Organ Size; Organogenesis; Signal Transduction; Somatomedins; Zoology
PubMed: 31615785
DOI: 10.1101/cshperspect.a037150 -
Cells Aug 2019The insulin like growth factor (IGF) axis plays a fundamental role in normal growth and development, and when deregulated makes an important contribution to disease.... (Review)
Review
The insulin like growth factor (IGF) axis plays a fundamental role in normal growth and development, and when deregulated makes an important contribution to disease. Here, we review the functions mediated by ligand-induced IGF axis activation, and discuss the evidence for the involvement of IGF signaling in the pathogenesis of cancer, endocrine disorders including acromegaly, diabetes and thyroid eye disease, skin diseases such as acne and psoriasis, and the frailty that accompanies aging. We discuss the use of IGF axis inhibitors, focusing on the different approaches that have been taken to develop effective and tolerable ways to block this important signaling pathway. We outline the advantages and disadvantages of each approach, and discuss progress in evaluating these agents, including factors that contributed to the failure of many of these novel therapeutics in early phase cancer trials. Finally, we summarize grounds for cautious optimism for ongoing and future studies of IGF blockade in cancer and non-malignant disorders including thyroid eye disease and aging.
Topics: Aging; Animals; Endocrine System Diseases; Humans; Mice; Molecular Targeted Therapy; Neoplasms; Rats; Receptor, IGF Type 1; Signal Transduction; Skin Diseases; Somatomedins
PubMed: 31416218
DOI: 10.3390/cells8080895 -
Experientia Supplementum (2012) 2016Chronic, age-associated diseases are already among the leading causes of morbidity and death in the world, a problem exacerbated by the rapidly rising proportion of... (Review)
Review
Chronic, age-associated diseases are already among the leading causes of morbidity and death in the world, a problem exacerbated by the rapidly rising proportion of elderly in the global population. This emergent epidemic represents the next great challenge for biomedical science and public health. Fortunately, decades of studies into the biology of aging have provided a head start by revealing an evolutionarily conserved network of genes that controls the rate and quality of the aging process itself and which can thereby be targeted for protection against age-onset disease. A number of dietary, genetic, and pharmacological interventions, including dietary restriction (DR) and the biguanide metformin, can extend healthy lifespan and reduce the incidence of multiple chronic conditions. Many of these interventions recurrently involve a core network of nutrient sensors: AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), the insulin/insulin-like growth factor signaling pathway (IIS), and the sirtuins. Here, we will summarize how AMPK acts downstream of these pro-longevity interventions and within this network of nutrient sensors to control the cell and physiological processes important for defining how well we age.
Topics: AMP-Activated Protein Kinases; Animals; Autophagy; Caenorhabditis elegans; Caloric Restriction; Energy Metabolism; Gene Expression Regulation; Humans; Insulin; Longevity; Metformin; Mitochondria; Protein Subunits; Signal Transduction; Sirtuins; Somatomedins; TOR Serine-Threonine Kinases
PubMed: 27812983
DOI: 10.1007/978-3-319-43589-3_10 -
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 -
Current Obesity Reports Jun 2017Adipocytes have adapted to store energy in the form of lipid and also secrete circulating factors called adipokines that signal to other tissues to coordinate energy... (Review)
Review
PURPOSE OF REVIEW
Adipocytes have adapted to store energy in the form of lipid and also secrete circulating factors called adipokines that signal to other tissues to coordinate energy homeostasis. These functions are disrupted in the setting of obesity, promoting the development of diseases such as diabetes, cardiovascular disease, and cancer.
RECENT FINDINGS
Obesity is linked to an increased risk of many types of cancer and increased cancer-related mortality. The basis for the striking association between obesity and cancer is not well understood. Here, we review the cellular and molecular pathways that appear to be involved in obesity-driven cancer. We also describe possible therapeutic considerations and highlight important unanswered questions in the field.
Topics: Adipocytes; Adipokines; Animals; Antineoplastic Agents; Comorbidity; Cytokines; Drug Repositioning; Energy Metabolism; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Inflammation Mediators; Insulin; Neoplasms; Obesity; Risk Factors; Signal Transduction; Somatomedins
PubMed: 28434109
DOI: 10.1007/s13679-017-0263-x -
Endocrinology Sep 2019Viruses have developed different mechanisms to manipulate their hosts, including the process of viral mimicry in which viruses express important host proteins. Until... (Review)
Review
Viruses have developed different mechanisms to manipulate their hosts, including the process of viral mimicry in which viruses express important host proteins. Until recently, examples of viral mimicry were limited to mimics of growth factors and immunomodulatory proteins. Using a comprehensive bioinformatics approach, we have shown that viruses possess the DNA/RNA with potential to encode 16 different peptides with high sequence similarity to human peptide hormones and metabolically important regulatory proteins. We have characterized one of these families, the viral insulin/IGF-1-like peptides (VILPs), which we identified in four members of the Iridoviridae family. VILPs can bind to human insulin and IGF-1 receptors and stimulate classic postreceptor signaling pathways. Moreover, VILPs can stimulate glucose uptake in vitro and in vivo and stimulate DNA synthesis. DNA sequences of some VILP-carrying viruses have been identified in the human enteric virome. In addition to VILPs, sequences with homology to 15 other peptide hormones or cytokines can be identified in viral DNA/RNA sequences, some with a very high identity to hormones. Recent data by others has identified a peptide that resembles and mimics α-melanocyte-stimulating hormone's anti-inflammatory effects in in vitro and in vivo models. Taken together, these studies reveal novel mechanisms of viral and bacterial pathogenesis in which the microbe can directly target or mimic the host endocrine system. These findings also introduce the concept of a system of microbial hormones that provides new insights into the evolution of peptide hormones, as well as potential new roles of microbial hormones in health and disease.
Topics: Animals; Endocrinology; Endothelin-1; Fish Diseases; Host-Pathogen Interactions; Humans; Insulin-Like Growth Factor I; Viral Proteins
PubMed: 31310273
DOI: 10.1210/en.2019-00271 -
Cells Oct 2020Since their discovery in the late 1950s, insulin-like growth factors (IGFs) have attracted significant interest in multiple areas of biology and medicine, including...
Since their discovery in the late 1950s, insulin-like growth factors (IGFs) have attracted significant interest in multiple areas of biology and medicine, including endocrinology, pediatrics, growth, metabolism, nutrition, aging, and oncology [...].
Topics: Aging; Animals; Endoplasmic Reticulum; Humans; Mice, Transgenic; Mitochondria; Neoplasms; Signal Transduction; Somatomedins
PubMed: 33080771
DOI: 10.3390/cells9102309 -
Journal of Animal Science May 2020Satellite cells are the myogenic stem and progenitor population found in skeletal muscle. These cells typically reside in a quiescent state until called upon to support... (Review)
Review
Satellite cells are the myogenic stem and progenitor population found in skeletal muscle. These cells typically reside in a quiescent state until called upon to support repair, regeneration, or muscle growth. The activities of satellite cells are orchestrated by systemic hormones, autocrine and paracrine growth factors, and the composition of the basal lamina of the muscle fiber. Several key intracellular signaling events are initiated in response to changes in the local environment causing exit from quiescence, proliferation, and differentiation. Signals emanating from Notch, wingless-type mouse mammary tumor virus integration site family members, and transforming growth factor-β proteins mediate the reversible exit from growth 0 phase while those initiated by members of the fibroblast growth factor and insulin-like growth factor families direct proliferation and differentiation. Many of these pathways impinge upon the myogenic regulatory factors (MRF), myogenic factor 5, myogenic differentiation factor D, myogenin and MRF4, and the lineage determinate, Paired box 7, to alter transcription and subsequent satellite cell decisions. In the recent past, insight into mouse transgenic models has led to a firm understanding of regulatory events that control satellite cell metabolism and myogenesis. Many of these niche-regulated functions offer subtle differences from their counterparts in livestock pointing to the existence of species-specific controls. The purpose of this review is to examine the mechanisms that mediate large animal satellite cell activity and their relationship to those present in rodents.
Topics: Animals; Cell Differentiation; Livestock; Mice; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Myogenic Regulatory Factor 5; Myogenic Regulatory Factors; Myogenin; Satellite Cells, Skeletal Muscle; Somatomedins
PubMed: 32175577
DOI: 10.1093/jas/skaa081