keyword
https://read.qxmd.com/read/38194365/ampk-mtorc1-pathway-mediates-hepatic-igfbp-1-phosphorylation-in-glucose-deprivation
#1
JOURNAL ARTICLE
Jenica H Kakadia, Muhammad U Khalid, Ilka U Heinemann, Victor Han
Mechanisms underlying limitations in glucose supply that restrict fetal growth are not well established. IGF-1 is an important regulator of fetal growth and IGF-1 bioavailability is markedly inhibited by IGFBP-1 especially when the binding protein is hyperphosphorylated. We hypothesized that the AMPK-mTORC1 pathway increases IGFBP-1 phosphorylation in response to glucose deprivation. Glucose deprivation in HepG2 cells activated AMPK and TSC2, inhibited mTORC1 and increased IGFBP-1 secretion and site-specific phosphorylation...
January 1, 2024: Journal of Molecular Endocrinology
https://read.qxmd.com/read/38182007/a-viral-insulin-like-peptide-inhibits-igf-1-receptor-phosphorylation-and-regulates-igf1r-gene-expression
#2
JOURNAL ARTICLE
Martina Chrudinová, Nicholas S Kirk, Aurelien Chuard, Hari Venugopal, Fa Zhang, Marta Lubos, Vasily Gelfanov, Terezie Páníková, Lenka Žáková, Julianne Cutone, Matthew Mojares, Richard DiMarchi, Jiří Jiráček, Emrah Altindis
OBJECTIVE: The insulin/IGF superfamily is conserved across vertebrates and invertebrates. Our team has identified five viruses containing genes encoding viral insulin/IGF-1 like peptides (VILPs) closely resembling human insulin and IGF-1. This study aims to characterize the impact of Mandarin fish ranavirus (MFRV) and Lymphocystis disease virus-Sa (LCDV-Sa) VILPs on the insulin/IGF system for the first time. METHODS: We chemically synthesized single chain (sc, IGF-1 like) and double chain (dc, insulin like) forms of MFRV and LCDV-Sa VILPs...
January 3, 2024: Molecular Metabolism
https://read.qxmd.com/read/38101566/suppression-of-overactive-insulin-like-growth-factor-1-attenuates-trauma-induced-heterotopic-ossification-in-mice
#3
JOURNAL ARTICLE
Dong Mao, Kai Wang, Hong Jiang, Jingyi Mi, Xiaoyun Pan, Gang Zhao, Yongjun Rui
Heterotopic ossification (HO) is the ectopic bone formation in soft tissues. Aside from hereditary HO, traumatic HO is common after orthopedic surgery, combat-related injuries, severe burns, or neurologic injuries. Recently, mammalian target of rapamycin (mTOR) has been demonstrated to be involved in the chondrogenic and osteogenic processes of HO formation. However, its upstream signaling mechanism remains unknown. In this study, using an Achilles tendon puncture-induced HO model, we revealed that overactive insulin-like growth factor 1 (IGF-1) was involved in the progression of HO in mice...
December 13, 2023: American Journal of Pathology
https://read.qxmd.com/read/38018587/astragalus-polysaccharide-ameliorates-insulin-resistance-in-hepg2-cells-through-activating-the-stat5-igf-1-pathway
#4
JOURNAL ARTICLE
Xinxin Yue, Wei Hao, Min Wang, Yang Fu
BACKGROUND: Insulin resistance (IR) is considered as a major factor initiating type 2 diabetes mellitus and can lead to a reduction in glucose uptake that mainly occurs in the liver. Astragalus polysaccharide (APC), extracted from the traditional Chinese medicine, has been recorded to suppress IR. However, the underlying mechanism remains inadequately explored. METHODS: IR was induced in HepG2 cells which further underwent APC treatment. Cell viability was determined by cell counting kit-8 assay...
November 2023: Immunity, Inflammation and Disease
https://read.qxmd.com/read/38002338/furin-regulates-the-alveolarization-of-neonatal-lungs-in-a-mouse-model-of-hyperoxic-lung-injury
#5
JOURNAL ARTICLE
Shin Kato, Osuke Iwata, Hiroyuki Kato, Satoko Fukaya, Yukari Imai, Shinji Saitoh
Despite advances in treatment options, such as corticosteroid administration and less invasive respiratory support, bronchopulmonary dysplasia (BPD) remains an important prognostic factor in preterm infants. We previously reported that furin regulates changes in lung smooth muscle cell phenotypes, suggesting that it plays a critical role in BPD pathogenesis. Therefore, in this study, we aimed to evaluate whether it regulates the alveolarization of immature lungs through activating alveolarization-driving proteins...
November 16, 2023: Biomolecules
https://read.qxmd.com/read/37871755/total-flavonoids-of-litchi-chinensis-sonn-seed-inhibit-prostate-cancer-growth-in-bone-by-regulating-the-bone-microenvironment-via-inactivation-of-the-hgfr-nf-%C3%AE%C2%BAb-signaling-pathway
#6
JOURNAL ARTICLE
Weiquan Zhang, Tao Chen, Peilin Yang, Xiaolan Li, Dan Zhu, Zhiheng Su, Xin Yang, Ronghua Jin, Taijin Lan, Hongwei Guo
ETHNOPHARMACOLOGICAL RELEVANCE: Litchi chinensis Sonn. (Litchi) seed, a traditional Chinese medicine, is habitually used in the clinical treatment of prostate cancer (PCa)-induced bone pain. In our previous study, flavonoids have been identified as the active ingredient of litchi seed against PCa. However, its anti-tumor activities in bone and associated molecular mechanisms are still unclear. AIM OF THE STUDY: To investigate the effects and underlying mechanisms of total flavonoids of litchi seed (TFLS) on the growth of PCa in bone...
October 21, 2023: Journal of Ethnopharmacology
https://read.qxmd.com/read/37853848/arsenic-induced-igf-1-signaling-impairment-and-neurite-shortening-the-protective-roles-of-igf-1-through-the-pi3k-akt-axis
#7
JOURNAL ARTICLE
Churaibhon Wisessaowapak, Apichaya Niyomchan, Daranee Visitnonthachai, Naphada Leelaprachakul, Piyajit Watcharasit, Jutamaad Satayavivad
We recently reported that arsenic caused insulin resistance in differentiated human neuroblastoma SH-SY5Y cells. Herein, we further investigated the effects of sodium arsenite on IGF-1 signaling, which shares downstream signaling with insulin. A time-course experiment revealed that sodium arsenite began to decrease IGF-1-stimulated Akt phosphorylation on Day 3 after treatment, indicating that prolonged sodium arsenite treatment disrupted the neuronal IGF-1 response. Additionally, sodium arsenite decreased IGF-1-stimulated tyrosine phosphorylation of the IGF-1 receptor β (IGF-1Rβ) and its downstream target, insulin receptor substrate 1 (IRS1)...
October 18, 2023: Environmental Toxicology
https://read.qxmd.com/read/37779156/multifaceted-role-of-mtor-mammalian-target-of-rapamycin-signaling-pathway-in-human-health-and-disease
#8
REVIEW
Vivek Panwar, Aishwarya Singh, Manini Bhatt, Rajiv K Tonk, Shavkatjon Azizov, Agha Saquib Raza, Shinjinee Sengupta, Deepak Kumar, Manoj Garg
The mammalian target of rapamycin (mTOR) is a protein kinase that controls cellular metabolism, catabolism, immune responses, autophagy, survival, proliferation, and migration, to maintain cellular homeostasis. The mTOR signaling cascade consists of two distinct multi-subunit complexes named mTOR complex 1/2 (mTORC1/2). mTOR catalyzes the phosphorylation of several critical proteins like AKT, protein kinase C, insulin growth factor receptor (IGF-1R), 4E binding protein 1 (4E-BP1), ribosomal protein S6 kinase (S6K), transcription factor EB (TFEB), sterol-responsive element-binding proteins (SREBPs), Lipin-1, and Unc-51-like autophagy-activating kinases...
October 2, 2023: Signal Transduction and Targeted Therapy
https://read.qxmd.com/read/37719369/translocation-of-igf-1r-in-endoplasmic-reticulum-enhances-serca2-activity-to-trigger-ca-2-er-perturbation-in-hepatocellular-carcinoma
#9
JOURNAL ARTICLE
Yanan Li, Keqin Li, Ting Pan, Qiaobo Xie, Yuyao Cheng, Xinfeng Wu, Rui Xu, Xiaohui Liu, Li Liu, Jiangming Gao, Wenmin Yuan, Xianjun Qu, Shuxiang Cui
The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1R β is translocated into the ER by β -arrestin2 ( β -arr2)...
September 2023: Acta Pharmaceutica Sinica. B
https://read.qxmd.com/read/37521868/activation-of-insulin-like-growth-factor-1-receptor-igf-1r-promotes-growth-of-colorectal-cancer-through-triggering-the-mex3a-mediated-degradation-of-rig-i
#10
JOURNAL ARTICLE
Qiaobo Xie, Yanyan Chu, Wenmin Yuan, Yanan Li, Keqin Li, Xinfeng Wu, Xiaohui Liu, Rui Xu, Shuxiang Cui, Xianjun Qu
Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active β -arrestin-2 scaffolds this disobliging signaling to talk with MEX3A...
July 2023: Acta Pharmaceutica Sinica. B
https://read.qxmd.com/read/37446291/lar-downregulation-protects-the-astrocytic-u251-and-cocultured-sh-sy5y-cells-in-a-rotenone-induced-parkinson-s-disease-cell-model
#11
JOURNAL ARTICLE
Wei Zheng, Xiao Han, Bing Han, Gang Li, Jing Gan, Tian Wang, Bo Xu, Jie He, Wenxiao Du, Xiaolin Cao, Zhenhua Wang
Leukocyte common antigen-related protein tyrosine phosphatase (LAR) is a member of the protein tyrosine phosphatase family that serves as a key regulator of cellular survival. It is also involved in neurodevelopment and brain disorders. This study was designed to investigate the role of LAR in a cell-based model of Parkinson's disease (PD) in which U251 and SH-SY5Y cells were used as models of astrocytes and dopaminergic neurons, respectively. Cell viability, cell death, cell morphology, protein phosphorylation and expression, ATP levels, reactive oxygen species (ROS) generation, and mitochondrial membrane potential were analyzed in the wild-type (WT) and heterozygous LAR-knockout astrocytoma U251 cells to assess the cell state, signal transduction, and mitochondrial function...
July 5, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37395917/igf-1-combined-with-opn-promotes-neuronal-axon-growth-in-vitro-through-the-igf-1r-akt-mtor-signaling-pathway-in-lipid-rafts
#12
JOURNAL ARTICLE
Qin Zhao, Hong Su, Wei Jiang, Haodong Luo, Lu Pan, Yuan Liu, Ce Yang, Ying Yin, Lehua Yu, Botao Tan
This study aims to investigate the effect of insulin-like growth factor 1 (IGF-1) combined with osteopontin (OPN) on the protein expression levels and growth of neuronal axons and its possible mechanism. In this study, IGF-1 combined with OPN promoted neuronal axon growth through the IGF-1R/Akt/mTOR signaling pathway in lipid rafts, and the effect was better than that of either agent alone. This effect was suppressed when given the mTOR inhibitor rapamycin or the lipid raft cholesterol extraction agent methyl-β-cyclodextrin (M-β-CD)...
July 3, 2023: Neurochemical Research
https://read.qxmd.com/read/37185810/feeding-enhances-fibronectin-adherence-of-quiescent-lymphocytes-through-non-canonical-insulin-signalling
#13
JOURNAL ARTICLE
Abhiram Charan Tej Mallu, Sivapriya Sivagurunathan, Debasish Paul, Hobby Aggarwal, Abel Arul Nathan, Amrutha Manikandan, Mahalakshmi M Ravi, Ramanamurthy Boppana, Kumaravelu Jagavelu, Manas Kumar Santra, Madhulika Dixit
Nutritional availability during fasting and refeeding affects the temporal redistribution of lymphoid and myeloid immune cells among the circulating and tissue-resident pools. Conversely, nutritional imbalance and impaired glucose metabolism are associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent immune cell function and trafficking are scanty...
April 25, 2023: Immunology
https://read.qxmd.com/read/37108437/placental-remote-control-of-fetal-metabolism-trophoblast-mtor-signaling-regulates-liver-igfbp-1-phosphorylation-and-igf-1-bioavailability
#14
JOURNAL ARTICLE
Fredrick J Rosario, Anand Chopra, Kyle Biggar, Theresa L Powell, Madhulika B Gupta, Thomas Jansson
The mechanisms mediating the restricted growth in intrauterine growth restriction (IUGR) remain to be fully established. Mechanistic target of rapamycin (mTOR) signaling functions as a placental nutrient sensor, indirectly influencing fetal growth by regulating placental function. Increased secretion and the phosphorylation of fetal liver IGFBP-1 are known to markedly decrease the bioavailability of IGF-1, a major fetal growth factor. We hypothesized that an inhibition of trophoblast mTOR increases liver IGFBP-1 secretion and phosphorylation...
April 14, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37034500/ag1024-an-igf-1-receptor-inhibitor-ameliorates-renal-injury-in-rats-with-diabetic-nephropathy-via-the-socs-jak2-stat-pathway
#15
JOURNAL ARTICLE
Jianhua Liu, Yun Zhang, Min Liu, Feng Shi, Bo Cheng
Insulin-like-growth factor-1 (IGF-1) is the ligand for insulin-like growth factor-1 receptor (IGF-1R), and the roles of IGF-1/IGF-1R in diabetic nephropathy (DN) are well-characterized previously. However, the biological functions of AG1024 (an IGF-1R inhibitor) in DN remain unknown. This study investigates the roles and related mechanisms of AG-1024 in DN. The experimental DN was established via intraperitoneal injection of streptozotocin, and STZ-induced diabetic rats were treated with AG1024 (20 mg/kg/day) for 8 weeks...
2023: Open Medicine (Warsaw, Poland)
https://read.qxmd.com/read/37021069/dab2-promotes-pulmonary-fibrosis-and-may-act-as-an-intermediate-between-igf%C3%A2-1r-and-pi3k-akt-signaling-pathways
#16
JOURNAL ARTICLE
Chun-Lian Liang, Xiu-Li Li, Xiao-Juan Quan, Lin Zhang
Idiopathic pulmonary fibrosis (IPF) is a heterogeneous lung disease associated with high mortality. Disabled-2 (DAB2), an adapter protein, regulates cell-fibrinogen adhesion and fibrinogen uptake. DAB2 is differentially expressed in mouse fibrotic lungs induced by bleomycin according to a genome microarray analysis based on Gene Expression Omnibus database. However, the role of DAB2 in IPF has not been revealed. A bleomycin-induced mouse model of pulmonary fibrosis was constructed in the present study. It found that the expression of DAB2 was upregulated in bleomycin-induced fibrotic lung tissue with collagen fiber deposition and pulmonary interstitium thickening...
April 2023: Experimental and Therapeutic Medicine
https://read.qxmd.com/read/37018819/mechanism-of-myocardial-fibrosis-regulation-by-igf-1r-in-atrial-fibrillation-through-the-pi3k-akt-foxo3a-pathway
#17
JOURNAL ARTICLE
Pei Zhang, Huilin Li, An Zhang, Xiao Wang, Qiyuan Song, Zhan Li, Weizong Wang, Jingwen Xu, Yinglong Hou, Yong Zhang
Atrial structural remodeling takes on a critical significance to the occurrence and maintenance of atrial fibrillation (AF). As revealed by recent data, insulin-like growth factor-1 receptor (IGF-1R) plays a certain role in tissue fibrosis. In this study, the mechanism of IGF-1R in atrial structural remodeling was examined based on in vivo and in vitro experiments. First, cluster analysis of AF hub genes was conducted, and then the molecular mechanism was proposed by which IGF-1R regulates myocardial fibrosis via the PI3K/Akt/FoxO3a pathway...
April 5, 2023: Biochemistry and Cell Biology
https://read.qxmd.com/read/36951642/igf-1-microinjection-in-the-prefrontal-cortex-attenuates-fentanyl-seeking-behavior-in-mice
#18
JOURNAL ARTICLE
Guohui Li, Shuwen Yue, Yunwanbin Wang, Archana Singh, Zi-Jun Wang
BACKGROUND: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder with an enormous socioeconomic burden. Opioid overdose deaths have reached an epidemic level, especially for fentanyl. One of the biggest challenges to treat OUD is the relapse to drug seeking after prolonged abstinence. Abnormalities in insulin-like growth factor-1 (IGF-1) have been reported in various neurological and psychiatric disorders, including OUD. However, whether IGF-1 and its downstream signaling pathways are associated with relapse to fentanyl seeking remains unclear...
March 23, 2023: International Journal of Neuropsychopharmacology
https://read.qxmd.com/read/36891560/recombinant-insulin-like-growth-factor-1-dimers-receptor-binding-affinities-and-activation-abilities
#19
JOURNAL ARTICLE
Jingjing Lin, Seiya Asai, Irena Selicharová, Katarína Mitrová, Jakub Kaminský, Elinor Young, Jiří Jiráček
UNLABELLED: Insulin-like growth factor 1 (IGF-1) and its IGF-1 receptor (IGF-1R) belong to an important biological system that is involved in the regulation of normal growth, but that has also been recognized as playing a role in cancer. IGF-1R antagonists could be interesting for the testing of their potential antiproliferative properties as an alternative to IGF-1R tyrosine-kinase inhibitors or anti-IGF-1R monoclonal antibodies. In this study, we were inspired by the successful development of insulin dimers capable of antagonizing insulin effects on the insulin receptor (IR) by simultaneous binding to two separated binding sites and by blocking structural rearrangement of the IR...
2023: International Journal of Peptide Research and Therapeutics
https://read.qxmd.com/read/36774408/targeting-the-e3-ligase-nedd4-as-a-novel-therapeutic-strategy-for-igf1-signal-pathway-driven-gastric-cancer
#20
JOURNAL ARTICLE
Ke Wang, Yanping Yu, Wei Wang, Yu Jiang, Yunlong Li, Xunliang Jiang, Yihuan Qiao, Le Chen, Xinhui Zhao, Jun Liu, Angang Yang, Jipeng Li, Rui Zhang
The IGF1 signal pathway is highly activated in some subtype of gastric cancer(GC) that exhibits poor survival and chemotherapy resistance. Although the results of clinical trials of anti-IGF1R monoclonal antibodies and IGF-1R inhibitors have been mostly disappointing in unselected cancer patients, some patients benefit from anti-IGF1R therapy in these failed studies. Therefore, it is necessary to characterize the complex IGF signaling in GC and help refine the strategies targeting the IGF1 pathway. We found that GC cell lines exhibit differential responses to the specific IGF1R inhibitor OSI906...
March 2023: Oncogene
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