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Journal of Clinical Neuroscience :... Dec 2022
Topics: Humans; Acromegaly; Cephalometry; Insulin-Like Growth Factor I
PubMed: 36327793
DOI: 10.1016/j.jocn.2022.09.020 -
Journal of Diabetes Research 2022Several epidemiological studies have identified diabetes as a risk factor for colorectal cancer (CRC). The potential pathophysiological mechanisms of this association... (Review)
Review
Several epidemiological studies have identified diabetes as a risk factor for colorectal cancer (CRC). The potential pathophysiological mechanisms of this association include hyperinsulinemia, insulin-like growth factor (IGF) axis, hyperglycemia, inflammation induced by adipose tissue dysfunction, gastrointestinal motility disorder, and impaired immunological surveillance. Several studies have shown that underlying diabetes adversely affects the prognosis of patients with CRC. This review explores the novel anticancer agents targeting IGF-1R and receptor for advanced glycation end products (RAGE), both of which play a vital role in diabetes-induced colorectal tumorigenesis. Inhibitors of IGF-1R and RAGE are expected to become promising therapeutic choices, particularly for CRC patients with diabetes. Furthermore, hypoglycemic therapy is associated with the incidence of CRC. Selection of appropriate hypoglycemic agents, which can reduce the risk of CRC in diabetic patients, is an unmet issue. Therefore, this review mainly summarizes the current studies concerning the connections among diabetes, hypoglycemic therapy, and CRC as well as provides a synthesis of the underlying pathophysiological mechanisms. Our synthesis provides a theoretical basis for rational use of hypoglycemic therapies and early diagnosis and treatment of diabetes-related CRC.
Topics: China; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Humans; Incidence; Receptor for Advanced Glycation End Products; Risk Factors; Somatomedins
PubMed: 35296101
DOI: 10.1155/2022/1747326 -
International Journal of Molecular... Apr 2024The insulin-like growth factor (IGF) system has paracrine and endocrine roles in the central nervous system. There is evidence that IGF signalling pathways have roles in... (Review)
Review
The insulin-like growth factor (IGF) system has paracrine and endocrine roles in the central nervous system. There is evidence that IGF signalling pathways have roles in the pathophysiology of neurodegenerative disease. This review focusses on Alzheimer's disease and Parkinson's disease, the two most common neurodegenerative disorders that are increasing in prevalence globally in relation to the aging population and the increasing prevalence of obesity and type 2 diabetes. Rodent models used in the study of the molecular pathways involved in neurodegeneration are described. However, currently, no animal model fully replicates these diseases. Mice with triple mutations in , and show promise as models for the testing of novel Alzheimer's therapies. While a causal relationship is not proven, the fact that age, obesity and T2D are risk factors in both strengthens the case for the involvement of the IGF system in these disorders. The IGF system is an attractive target for new approaches to management; however, there are gaps in our understanding that first need to be addressed. These include a focus beyond IGF-I on other members of the IGF system, including IGF-II, IGF-binding proteins and the type 2 IGF receptor.
Topics: Humans; Animals; Neurodegenerative Diseases; Alzheimer Disease; Signal Transduction; Insulin-Like Growth Factor I; Somatomedins; Disease Models, Animal; Parkinson Disease; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Peptides
PubMed: 38674097
DOI: 10.3390/ijms25084512 -
Brain and Behavior Jan 2023We aimed to investigate if there is a significant difference in peripheral insulin-like growth factor 1 (IGF-1) levels between schizophrenia patients and healthy... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aimed to investigate if there is a significant difference in peripheral insulin-like growth factor 1 (IGF-1) levels between schizophrenia patients and healthy controls and to determine whether a difference exists before and after initiation of antipsychotics.
METHODS
PubMed/MEDLINE, Scopus, and Web of Science were searched up to March 27, 2022. Original clinical studies of any type that reported peripheral blood, serum or plasma IGF-1 levels measured after fasting in schizophrenia patients and/or healthy control group were selected based on inclusion and exclusion criteria. Data were analyzed using Meta-Essentials: Workbooks for meta-analysis and pooled through random-effects meta-analyses.
RESULTS
Twelve publications met eligibility criteria. Schizophrenia patients under antipsychotic treatment had significantly lower peripheral IGF-1 levels compared to healthy controls (n = 632, Hedges' g -0.42, 95% CI from -0.79 to -0.04, p = .006, I = 70.38%), while no significant difference was found between schizophrenia patients regardless of the antipsychotic treatment status and healthy controls, as well as between antipsychotic naïve or free schizophrenia patients and healthy controls, and before and after initiation of antipsychotic treatment. However, high heterogeneity was observed and its potential sources in some of the subgroup analyses included sample type and region.
CONCLUSIONS
Schizophrenia patients under antipsychotic treatment seem to have lower peripheral IGF-1 levels compared to healthy controls. Additional studies with larger and more homogenous samples are needed to confirm these findings.
Topics: Humans; Schizophrenia; Antipsychotic Agents; Insulin-Like Growth Factor I; Fasting
PubMed: 36448977
DOI: 10.1002/brb3.2819 -
Journal of Translational Medicine Feb 2020Parkinson's disease (PD) is a neurodegenerative disorder that results in the death of dopaminergic neurons within the substantia nigra pars compacta and the reduction in... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder that results in the death of dopaminergic neurons within the substantia nigra pars compacta and the reduction in dopaminergic control over striatal output neurons, leading to a movement disorder most commonly characterized by akinesia or bradykinesia, rigidity and tremor. Also, PD is less frequently depicted by sensory symptoms (pain and tingling), hyposmia, sleep alterations, depression and anxiety, and abnormal executive and working memory related functions. On the other hand, insulin-like growth factor 1 (IGF-1) is an endocrine, paracrine and autocrine hormone with several functions including tissue growth and development, insulin-like activity, proliferation, pro-survival, anti-aging, antioxidant and neuroprotection, among others. Herein this review tries to summarize all experimental and clinical data to understand the pathophysiology and development of PD, as well as its clear association with IGF-1, supported by several lines of evidence: (1) IGF-1 decreases with age, while aging is the major risk for PD establishment and development; (2) numerous basic and translational data have appointed direct protective and homeostasis IGF-1 roles in all brain cells; (3) estrogens seem to confer women strong protection to PD via IGF-1; and (4) clinical correlations in PD cohorts have confirmed elevated IGF-1 levels at the onset of the disease, suggesting an ongoing compensatory or "fight-to-injury" mechanism.
Topics: Brain; Dopamine; Female; Humans; Insulin-Like Growth Factor I; Neurons; Parkinson Disease
PubMed: 32046737
DOI: 10.1186/s12967-020-02223-0 -
Endocrine Reviews Jul 2023In metabolic conditions such as obesity and diabetes, which are associated with deregulated signaling of the insulin/insulin-like growth factor system (IIGFs),... (Review)
Review
In metabolic conditions such as obesity and diabetes, which are associated with deregulated signaling of the insulin/insulin-like growth factor system (IIGFs), inflammation plays a dominant role. In cancer, IIGFs is implicated in disease progression, particularly during obesity and diabetes; however, further mediators may act in concert with IIGFs to trigger meta-inflammation. The receptor for advanced glycation end-products (RAGE) and its ligands bridge together metabolism and inflammation in obesity, diabetes, and cancer. Herein, we summarize the main mechanisms of meta-inflammation in malignancies associated with obesity and diabetes; we provide our readers with the most recent understanding and conceptual advances on the role of RAGE at the crossroad between impaired metabolism and inflammation, toward disease aggressiveness. We inform on the potential hubs of cross-communications driven by aberrant RAGE axis and dysfunctional IIGFs in the tumor microenvironment. Furthermore, we offer a rationalized view on the opportunity to terminate meta-inflammation via targeting RAGE pathway, and on the possibility to shut its molecular connections with IIGFs, toward a better control of diabetes- and obesity-associated cancers.
Topics: Humans; Glycation End Products, Advanced; Inflammation; Insulin; Neoplasms; Obesity; Receptor for Advanced Glycation End Products; Somatomedins; Tumor Microenvironment
PubMed: 36869790
DOI: 10.1210/endrev/bnad005 -
Molecular Vision 2022Strabismus (STBMS) is a multifactorial ocular disorder in children that leads to misalignment of the eyes. Insulin-like growth factor 1 () has been shown to be involved...
PURPOSE
Strabismus (STBMS) is a multifactorial ocular disorder in children that leads to misalignment of the eyes. Insulin-like growth factor 1 () has been shown to be involved in the development of extraocular muscles and myopia; however, data are limited on the genetic associations of with STBMS in Pakistan.
METHODS
Two hundred seventy-four STBMS cases and 272 unaffected controls were recruited, and their DNA was extracted. Two single nucleotide polymorphisms, rs6214 and rs5742632, were genotyped using PCR-restriction fragment length polymorphism. Univariate logistic regression analysis was performed to determine the association of these single nucleotide polymorphisms with STBMS, and the results were adjusted for age and sex. In addition, 26 extraocular muscle tissues were collected from patients with STBMS undergoing squint correction surgery, along with 3 deceased control samples. mRNA expression was measured by quantitative PCR; the Mann-Whitney U test was applied, and fold change was calculated. Logistic regression analysis was applied to determine the association of RNA expression and fold change with genotype.
RESULTS
Multivariate logistic regression analysis revealed that rs5742632 (odds ratio [95% confidence interval] = 1.05[1.01-1.06], p = 0.03) is associated with STBM. Moreover, rs6214 (1.03[1.01-1.05], p = 0.03) and rs5742632 (1.09[1.04-1.11], p = 0.04) were associated with exotropia. Statistically, no significant difference in mRNA expression in the extraocular muscles between the STBMS cases and the controls was observed.
CONCLUSIONS
polymorphisms rs5742632 (A>G) and rs6214 (C>T) are plausible risk factors for the development of exotropia. However, the physiologic mechanism requires further evaluation.
Topics: Child; Humans; Insulin-Like Growth Factor I; Genetic Predisposition to Disease; Pakistan; Exotropia; Case-Control Studies; Polymorphism, Single Nucleotide; Genotype; RNA, Messenger
PubMed: 36338665
DOI: No ID Found -
Molecular Metabolism Oct 2021The insulin-like growth factor family of ligands (IGF-I, IGF-II, and insulin), receptors (IGF-IR, M6P/IGF-IIR, and insulin receptor [IR]), and IGF-binding proteins... (Review)
Review
BACKGROUND
The insulin-like growth factor family of ligands (IGF-I, IGF-II, and insulin), receptors (IGF-IR, M6P/IGF-IIR, and insulin receptor [IR]), and IGF-binding proteins (IGFBP-1-6) play critical roles in normal human physiology and disease states.
SCOPE OF REVIEW
Insulin and insulin receptors are the focus of other chapters in this series and will therefore not be discussed further. Here we review the basic components of the IGF system, their role in normal physiology and in critical pathology's. While this review concentrates on the role of IGFs in human physiology, animal models have been essential in providing understanding of the IGF system, and its regulation, and are briefly described.
MAJOR CONCLUSIONS
IGF-I has effects via the circulation and locally within tissues to regulate cellular growth, differentiation, and survival, thereby controlling overall body growth. IGF-II levels are highest prenatally when it has important effects on growth. In adults, IGF-II plays important tissue-specific roles, including the maintenance of stem cell populations. Although the IGF-IR is closely related to the IR it has distinct physiological roles both on the cell surface and in the nucleus. The M6P/IGF-IIR, in contrast, is distinct and acts as a scavenger by mediating internalization and degradation of IGF-II. The IGFBPs bind IGF-I and IGF-II in the circulation to prolong their half-lives and modulate tissue access, thereby controlling IGF function. IGFBPs also have IGF ligand-independent cell effects.
Topics: Animals; Cell Communication; Humans; Insulin-Like Growth Factor Binding Proteins; Ligands; Receptor, Insulin; Somatomedins
PubMed: 33962049
DOI: 10.1016/j.molmet.2021.101245 -
International Journal of Molecular... Nov 2023The insulin-like growth factor axis is a multifaceted, complex system that comprises two ligands, IGF-I and IGF-II, receptors (IGF-1R, IGF-IIR, insulin receptor isoforms...
The insulin-like growth factor axis is a multifaceted, complex system that comprises two ligands, IGF-I and IGF-II, receptors (IGF-1R, IGF-IIR, insulin receptor isoforms IR-A and B, and hybrid receptors) six high affinity IGF-binding proteins (IGFBPs 1-6), and IGFBP proteases [...].
Topics: Insulin-Like Growth Factor II; Insulin-Like Growth Factor I; Insulin-Like Growth Factor Binding Proteins; Protein Binding; Insulin-Like Growth Factor Binding Protein 6
PubMed: 38069291
DOI: 10.3390/ijms242316969 -
International Journal of Molecular... Jan 2021The insulin and insulin-like growth factor (IGF) system plays an important role in regulating normal cell proliferation and survival. However, the IGF system is also... (Review)
Review
The insulin and insulin-like growth factor (IGF) system plays an important role in regulating normal cell proliferation and survival. However, the IGF system is also implicated in many malignancies, including breast cancer. Preclinical studies indicate several IGF blocking approaches, such as monoclonal antibodies and tyrosine kinase inhibitors, have promising therapeutic potential for treating diseases. Uniformly, phase III clinical trials have not shown the benefit of blocking IGF signaling compared to standard of care arms. Clinical and laboratory data argue that targeting Type I IGF receptor (IGF1R) alone may be insufficient to disrupt this pathway as the insulin receptor (IR) may also be a relevant cancer target. Here, we review the well-studied role of the IGF system in regulating malignancies, the limitations on the current strategies of blocking the IGF system in cancer, and the potential future directions for targeting the IGF system.
Topics: Breast Neoplasms; Cell Proliferation; Cell Survival; Female; Humans; Insulin; Molecular Targeted Therapy; Receptor, IGF Type 1; Somatomedins
PubMed: 33429867
DOI: 10.3390/ijms22020555