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Insulin/IGF Signaling in Early Brain Development
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Selma Yagoub, Rachel N. Lippert
After the closure of the neural chord, the proliferation of neuronal cells occurs. This neurogenesis is mediated in part by insulin but has primarily been studied in the context of IGF signaling. Seminal studies have concentrated on the role of these peptides in neurogenesis in the chick embryonic retina. Further studies using in vitro models have confirmed the role of insulin, IGF-1 and IGF-2 as trophic factors for neurons in culture. Using cultured sympathetic neurons from 7-day-old chick embryos, insulin, IGF-1 and IGF-2 induced a significant increase in proliferation of this neuronal cell type (29). The specific action of IGF1 and IGF2 on this process was via the Insulin-like Growth Factor Binding Proteins (IGFBPs) rather than directly via receptor-mediated signaling. In primary fetal rat neuronal cells, IGF-1 increases the survival and expansion of neuronal and non-neuronal cell populations (30). Further, stimulation of growth of neural stem cells (NSCs) by other growth factors, such as EGF and FGF-2 requires the presence of IGF-1 (31). This effect is mediated by the phosphorylation of Akt/Bad/Bcl-2 signaling and the phosphorylation of Akt at Thr308 and Ser473 and is inhibited in the presence of excess PTEN, a protein phosphatase, as shown in Figure 2.1 (32, 33). The derivation of neural tissues from embryonic stem cells necessitates IGF-2 signaling via the IGF1-R and subsequent modulation of neural markers, SOX1, IRX3, and SIX3, further indicating a role of the IGF axis in neurogenesis and differentiation (34).
Genetics
Published in Rachel U Sidwell, Mike A Thomson, Concise Paediatrics, 2020
Rachel U Sidwell, Mike A Thomson
Gene Located at 11p15.5, with the maternal copy normally inactivated (imprinted). Imprinting occurs in the insulinlike growth factor 2 (IGF2) gene on chromosome 11. IGF2 is active only in the paternal copy, i.e. imprinted in the maternal copy. Therefore a double dose of IGF2 will occur with inheritance of both paternal copies, or Loss of maternal imprint (so the maternal gene is activated). The high Levels of IGF2 are thought to result in the clinical features.
Malignant Solitary Fibrous Tumor of the Pleura Associated with a Paraneoplastic Hypoglycemia
Published in Wickii T. Vigneswaran, Thoracic Surgery, 2019
Evgeny V. Arshava, Adnan Al Ayoubi, Kalpaj R. Parekh
NIMH in the setting of PSFT, or Doege–Potter syndrome, is present in <5% of cases of SFTs and is the result of the tumor-secreting insulin-like growth factors (IGF) 2. In NIMH, the serum levels of insulin, C-peptide, and IGF 1 are usually decreased or undetectable. In some cases, total IGF 2 level may be increased, decreased, or normal. Many IGF 2 proteins have a higher molecular weight (“big” IGF) and are not detectable by conventional immunometric assay. In such cases, including ours, while both IGF 1 and total IGF 2 may be within the reference range, the relative excess of IGF 2 over IGF 1 can bind insulin receptors and lead to hypoglycemia [3].
Non-islet cell tumor-induced hypoglycemia in the setting of metastatic intracranial hemangiopericytoma: case report and review of the literature
Published in British Journal of Neurosurgery, 2023
Leslie A. Nussbaum, Rebecca M. Walton, Eric S. Nussbaum
Proposed mechanisms of hypoglycemia caused by metastatic hemangiopericytoma include increased glucose utilization by the tumor, suppression of hepatic glucose production, and abnormal secretion of hormones involved in glucose homeostasis.5,13 Our literature review demonstrated low levels of insulin in 6/8 cases (75%), insulin-like growth factor 1 (IGF-1) in 8/8 cases (100%), and growth hormone (GH) in 4/4 cases; compared to normal ranges.8,10 Levels of insulin, IGF-1, C-peptide, and GH are reported to decrease when IGF-2 levels are elevated.16–19 However, increased levels of IGF-2 only occurred in 3/7 cases in our literature review. A high ratio of IGF-2:IGF-1 (>10) might suggest increased levels of IGF-2 precursor secretion.13 Indeed, the IGF-2:IGF-1 ratio ranged from 14 to 296 reported in all 8 cases of our literature review. With early diagnosis, a combined approach of surgical resection, radiation therapy, chemotherapy, and corticosteroid treatment can be used successfully to control hypoglycemic episodes.10,13,14
Bioinformatic Identification of Hub Genes and Analysis of Prognostic Values in Colorectal Cancer
Published in Nutrition and Cancer, 2021
Xinyi Lei, Jing Jing, Miao Zhang, Bingsheng Guan, Zhiyong Dong, Cunchuan Wang
A comprehensive elucidation of CRC initiation, progression, and metastasis will be helpful for the early diagnosis and precise treatment of CRC patients. The last study has demonstrated the signaling pathway of insulin-like growth factor-2 (IGF-2), which has the significance in initiation, progression, prognosis, and treatment in CRC (4). Another new study has shown that circulating tumor DNA (ctDNA) is considered as a meaningful prognostic indicator in stage III CRC, post-chemotherapy ctDNA may reveal CRC patients at high risk of recurrence despite completing chemotherapy (5). The sequence study has shown that some special non-coding RNA, such as has_circ_0067163, has_circ_0140188, has_circ_0002632, and so on, are related to CRC (6). An in-depth understanding of CRC's molecular biology can be beneficial for the diagnosis and treatment of CRC.
Incorporating molecular biomarkers into clinical practice for gastric cancer
Published in Expert Review of Anticancer Therapy, 2019
Shunsuke Nakamura, Mitsuro Kanda, Yasuhiro Kodera
Insulin-like growth factor 2 (IGF2) is mitogenic and antiapoptotic. IGF2 is an imprinted gene, expressed predominantly from the paternal allele, and its expression is controlled by CpG-rich regions (differentially methylated regions [DMRs]). Biallelic expression of IGF2 is a common epigenetic aberration in human cancers that increases the expression of genes involved in mitosis [60]. Tahara et al [60] . investigated IGF2 DMRs and the methylation of long interspersed nucleotide element (LINE1) in leukocyte DNA and their associations with patients’ clinical features. In patients with GC, hypomethylation of IGF2 DMRs and LINE1 is significantly associated with advanced age. Hypermethylation of IGF2 DMRs and LINE1 is significantly associated with undifferentiated histologic type, advanced stage, lymphatic invasion positive, venous invasion, lymph node metastasis, peritoneal dissemination, liver metastasis, and metastases to other sites.