China
Africa
Explore chapters and articles related to this topic
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).
Lifestyle Factors in Cancer Survivorship
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Insulin-like growth factor (IGF-1) and its binding proteins, insulin-like growth factor binding proteins (IGFBPs), have a central role in the regulation of cell growth. After binding to its receptor tyrosine kinase, IGF-1 activates several signaling pathways, leading to the inhibition of apoptosis, the promotion of cell growth, and angiogenesis. Higher levels of IGF-1 would therefore be expected to increase tumor growth and have been reported to be associated with a greater cancer risk. An inverse relationship is reported with IGF binding protein (IGFBP3) levels, although this effect has not been confirmed in all studies. Exercise has been shown to increase the levels of IGFBP3 and lower IGF-1, and in a large prospective cohort study of 41,528 participants, this was associated with a 48% reduction of cancer-specific deaths. Decreased levels of IGF-1 in physically active patients have also been linked to an improved survival.
Senescent Cells as Drivers of Age-Related Diseases
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Cielo Mae D. Marquez, Michael C. Velarde
Senescent cells are marked by their inability to divide and by their dramatic changes in morphology and metabolic processes. Senescent cells are characterized by their enlarged cell size and flattened cytoplasm compared to the normal cell morphology in proliferating, quiescent, or terminally differentiated cells (Figure 16.1). Senescent phenotypes also include development of nuclear blebbing, increase in lysosomal mass, increased activity of the pH-dependent senescence-associated β-galactosidase (SA β-gal), downregulation of lamin B1, formation of senescence-associated heterochromatin foci (SAHF), establishment of DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS), activation of p53/p21 and p16/pRb pathways, and secretion of high mobility group box 1 (HMGB1) (Figure 16.2) [19–23]. Cells that undergo senescence develop resistance to apoptosis partly due to the absence of insulin-like growth factor-binding protein 3 (IGFBP-3) within the nucleus [4]. Senescent cells also express many cytokines, chemokines, growth factors, and other proteins collectively termed as the senescence-associated secretory phenotype (SASP) [24,25].
Lower serum insulin-like growth factor-1 levels are independently associated with anemia in patients undergoing maintenance hemodialysis
Published in Renal Failure, 2023
Shilin Xu, Jun Ren, Yuping Yao, Danping Qin, Yan Liu, Xiaoshi Zhong, Rongshao Tan, Chunjie Jiang, Yun Liu, Wenxuan Chen
Intervention studies have shown that in malnourished patients undergoing dialysis [22] and older adults [23], short-term treatment with recombinant human growth hormone (GH) could increase hemoglobin levels and thus improve anemia. By regulating the amount of IGF-1 synthesized and released by the liver or by modulating the plasma concentrations of IGF-1-binding proteins, GH can affect the amount of free IGF-1 bound to receptors on the cell surface, which reflects the bioavailability of IGF-1. Disturbances in GH and IGF-1 bioavailability may lead to renal anemia [24]. Kim et al. found that the levels of free IGF-1 and its bioactivity in patients undergoing MHD were approximately half of those observed in healthy participants. During dialysis, the bioactivity of IGF-1 decreases by >50%. Insulin-like growth factor-binding proteins (IGFBPs) are important regulators of IGF-1 action. Reduced renal clearance leads to the accumulation of intact and partially degraded IGFBPs in serum, resulting in the downregulation of free IGF-1 levels and activity [25]. In summary, IGF-1 may be an important factor in the regulation of erythropoiesis in patients with CKD. Although during our literature search, we found that most studies on the relationship between serum IGF-1 and hemoglobin in patients with CKD or on dialysis were published in the late 20th and early 21st centuries, no study has yet to show that exogenous IGF-1 preparations can improve anemia in this population.
Toxicoproteomics reveals an effect of clozapine on autophagy in human liver spheroids
Published in Toxicology Mechanisms and Methods, 2023
Catherine Nury, Celine Merg, Yvan Eb-Levadoux, David Bovard, Matthieu Porchet, Fabio Maranzano, Isidora Loncarevic, Shahrzad Tavalaei, Eleonore Lize, Ramona Liliana Demenescu, Hasmik Yepiskoposyan, Julia Hoeng, Nikolai V Ivanov, Kasper Renggli, Bjoern Titz
Evaluation of the protein changes upon TNFα + IL-1β treatment by GSA indicated the expected perturbation of several immune-related gene/protein sets, including cytokine, inflammasome, and innate immune cell-related gene/protein sets (Supplementary Table 2). Most of the protein levels affected by TNFα + IL-1β treatment did not significantly change upon clozapine treatment (Figure 2(B)), suggesting that clozapine did not induce a broad inflammatory response in liver spheroid cultures. However, interferon gamma receptor 1 (IFNGR1) was significantly upregulated by both TNFα + IL-1β and 60 µM clozapine treatment. IFNGR1 upregulation in the liver has been observed upon exposure to liver toxicants (Jellali et al. 2021), and IFN-γ has been found to affect the fate of hepatocytes (Horras et al. 2011). Insulin-like growth factor-binding protein 1 (IGFBP1) was strongly upregulated by both treatments. IGFBP1 is associated with autophagy regulation (Galluzzi et al. 2014).
The common variant of rs6214 in insulin like growth factor 1 (IGF1) gene: a potential protective factor for non-alcoholic fatty liver disease
Published in Archives of Physiology and Biochemistry, 2023
Mohammad Sabzikarian, Touraj Mahmoudi, Seidamir Pasha Tabaeian, Gholamreza Rezamand, Asadollah Asadi, Hamid Farahani, Hossein Nobakht, Reza Dabiri, Fariborz Mansour-Ghanaei, Faramarz Derakhshan, Mohammad Reza Zali
The insulin axis and insulin-like growth factor (IGF) axis are biologically interrelated. Insulin like growth factor 1 (product of the IGF1 gene) and insulin-like growth factor-binding protein 3 (product of the IGFBP3 gene) are directly involved in insulin-signalling pathway. IGF1 is mostly synthesised and secreted by the liver and is similar in molecular structure and function to insulin. On the other hand, IGFBP3 regulates the bioavailability of IGF1 to the target tissues. Furthermore, insulin increases the expression and bioavailability of IGF1 via decreases the synthesis of IGFBPs, especially IGFBP3 (Giovannucci 2001). Circulating IGF1 level is inversely associated with reduced insulin sensitivity (Succurro et al. 2009), and its low level is an independent predictor for the development of glucose intolerance (Sandhu et al. 2002). Consistently, liver-specific IGF1 knockout mice exhibit IR and hyperinsulinemia (Yakar et al. 2001). More interestingly, circulating levels of IGF1 and its mRNA expression levels are lower in patients with NAFLD than in the controls (Sumida et al. 2015, Chishima et al. 2017, Yao et al. 2019). Based on these considerations, we designed the present study to examine the possible association of IGF1 (rs6214) and IGFBP3 (rs3110697) gene variants with NAFLD risk.