Modulation of<i>IGF1R</i>Signaling Pathway by<i>GIGYF1</i>in High Glucose-Induced SHSY-5Y Cells

Zhou, Ting; Ma, Yuefei; Tang, Juan; Guo, Fengqi; Dong, Mei; Wei, Quan

doi:10.1089/dna.2018.4336

Cited by 5 publications

(7 citation statements)

References 40 publications

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“…The third gene which is exome wide significant, GIGYF1 , has not previously been implicated in the aetiology of diabetes. Its product binds to growth factor receptor‐bound protein 10 (GRB10) and has a role in modulating the insulin‐like growth factor (IGF1) receptor signalling pathway 27,28 . A variant in GRB10 has been reported to be associated with decreased early‐phase insulin secretion and the muscle‐specific ablation of Grb10 in mice causes increased glucose uptake into muscles with increased insulin signalling 29,30 …”

Section: Discussionmentioning

confidence: 99%

“…and has a role in modulating the insulin-like growth factor (IGF1) receptor signalling pathway. 27,28 A variant in GRB10 has been reported to be associated with decreased early-phase insulin secretion and the muscle-specific ablation of Grb10 in mice causes increased glucose uptake into muscles with increased insulin signalling. Alad is reduced in rats with high-fat diet-induced weight gain and inhibition of ALAD with aminotriazole led to reduced glucose uptake in cultured human adipocytes.…”

Section: Curtismentioning

confidence: 99%

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Analysis of rare coding variants in 200,000 exome‐sequenced subjects reveals novel genetic risk factors for type 2 diabetes

Curtis

2021

Diabetes Metabolism Res

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Aims The study aimed to elucidate the effects of rare genetic variants on the risk of type 2 diabetes (T2D). Materials and methods Weighted burden analysis of rare variants was applied to a sample of 200,000 exome‐sequenced participants in the UK Biobank project, of whom over 13,000 were identified as having T2D. Variant weights were allocated based on allele frequency and predicted effect, as informed by a previous analysis of hyperlipidaemia. Results There was an exome‐wide significant increased burden of rare, functional variants in three genes, GCK, HNF4A and GIGYF1. GIGYF1 has not previously been identified as a diabetes risk gene and its product appears to be involved in the modification of insulin signalling. A number of other genes did not attain exome‐wide significance but were highly ranked and potentially of interest, including ALAD, PPARG, GYG1 and GHRL. Loss of function (LOF) variants were associated with T2D in GCK and GIGYF1 whereas nonsynonymous variants annotated as probably damaging were associated in GCK and HNF4A. Overall, fewer than 1% of T2D cases carried one of these variants. In HNF1A and HNF1B there was an excess of LOF variants among cases but the small numbers of these fell short of statistical significance. Conclusions Rare genetic variants make an identifiable contribution to T2D in a small number of cases but these may provide valuable insights into disease mechanisms. As larger samples become available it is likely that additional genetic factors will be identified.

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Section: Discussionmentioning

confidence: 99%

Section: Curtismentioning

confidence: 99%

Analysis of rare coding variants in 200,000 exome‐sequenced subjects reveals novel genetic risk factors for type 2 diabetes

Curtis

2021

Diabetes Metabolism Res

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“…It can combine with AKT and EGFR to form a macromolecular protein complex, which plays an important role in regulating cell apoptosis (16). Besides, it can bind to Grb10 that can activate tyrosine kinase receptors (such as insulin growth factor receptor and insulin receptor), so as to regulate nutrient metabolism and cell growth and proliferation in vivo (17,18). The latter can also promote the expression of downstream ERK1/2 and promote cell transcription and translation (19).…”

Section: Intervention On Mir-145-5p Expression Inhibited Excessive Ap...mentioning

confidence: 99%

“…In addition to binding to Grb10, GIGYF1 protein can also interact with AKT, EGFR and other factors to form macromolecular protein complex to regulate cell apoptosis (16), supporting its role in mediating the process of cell apoptosis. Meanwhile, Grb10 can activate tyrosine kinase receptors, including insulin growth factor receptor (IGF-1) and insulin receptor (17). Through binding to Grb10, GIGYF1 may regulate the insulin receptor signaling pathway, which can regulate the metabolic process of various nutrients in vivo and promote cell growth and proliferation (18).…”

Section: Introductionmentioning

confidence: 99%

“…Through binding to Grb10, GIGYF1 may regulate the insulin receptor signaling pathway, which can regulate the metabolic process of various nutrients in vivo and promote cell growth and proliferation (18). In addition, considering that Grb10 can promote the expression of downstream ERK1/2 to promote cell transcription and translation (17,19). Therefore, GIGYF1 may indirectly regulate cell growth and proliferation by binding with Grb10.…”

Section: Introductionmentioning

confidence: 99%

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Effects of miR-145-5p on cardiomyocyte proliferation and apoptosis, GIGYF1 expression and oxidative stress response in rats with myocardial ischemia-reperfusion

Liang

Wang

Zhao³

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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This study aimed to investigate the effects of miR-145-5p on cardiomyocyte proliferation and apoptosis, GIGYF1 expression, inflammation, and oxidative stress in rats with myocardial ischemia-reperfusion injury (IRI). For this purpose, SPF male SD rats were used for IRI modeling. Experimental animals were subjected to specimen sampling and myocardial HE staining. The relative expression of miR-145-5p was detected by qRT-PCR; the protein expressions of GIGYF1, p-AKT, p53, Bax, p38MAPK, and ERK1/2 were detected by Western blot. Mouse embryonic cardiomyocytes H9C2 were used for H/R modeling, which was then subjected to cell transfection according to different grouping protocols. The target of miR-145-5p was confirmed to be GIGYF1 by dual-luciferase reporter assay. Further experiments were performed to detect the survival rate of transfected cells, the apoptosis of transfected cells, SOD activity determination, as well as IL-1β and IL-6 concentrations. The results showed that the expression level of miR-145-5p was downregulated in H2C2 cells (P < 0.05). After 24h of transfection, there was a significant increase in the expression of miR-145-5p in the H/R+miR-145-5p mimic group (P < 0.05), but an evident decrease in the H/R+miR-145-5p inhibitor group (P > 0.05). Compared with the H/R+NC inhibitor group, the H/R+miR-145-5p mimic group had significantly increased cell proliferation, improved release of SOD, and upregulated expressions of ERK1/2 and p-AKT; but downregulated concentrations of IL-1β and IL-6, and decreased expressions of P38MAPK, p53, and Bax (all P < 0.05). Also, the IRI+miR-145-5p agomir group had significantly upregulated expression of miR-145-5p and improved injury degree of heart tissue improved; a significant increase in the protein expressions ERK1/2 and p-AKT, but downregulated protein expressions of P38MAPK, p53, and Bax (all P < 0.05). Dual-luciferase reporter assay identified that GIGYF1 was the target gene of miR-145-5p. Furthermore, through the stimulated overexpression of miR-145-5p, there were significantly increased cell proliferation, improved release of SOD, and upregulated expressions of ERK1/2 and p-AKT; but downregulated concentrations of IL-1β and IL-6, and decreased expressions of P38MAPK, p53, and Bax (all P < 0.05), while the above trends were reversed following the simultaneous upregulation of miR-145-5p and GIGYF1 (all P < 0.05). In general, our study confirmed a decreased expression of miR-145-5p and increased expression of GIGYF1 in the IRI or H/R model in vivo and in vitro. Overexpression of miR-145-5p can downregulate the expression of GIGYF1, further promote cell proliferation, inhibit cell apoptosis, alleviate inflammation and oxidative stress, and hence exert a protective role in myocardial infarction IRI.

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Therapeutic targets for endometriosis: Genome-wide Mendelian randomization and colocalization analyses

Zeng,

Lu,

Zhang

et al. 2024

Gene

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Modulation ofIGF1RSignaling Pathway byGIGYF1in High Glucose-Induced SHSY-5Y Cells

Cited by 5 publications

References 40 publications

Analysis of rare coding variants in 200,000 exome‐sequenced subjects reveals novel genetic risk factors for type 2 diabetes

Analysis of rare coding variants in 200,000 exome‐sequenced subjects reveals novel genetic risk factors for type 2 diabetes

Effects of miR-145-5p on cardiomyocyte proliferation and apoptosis, GIGYF1 expression and oxidative stress response in rats with myocardial ischemia-reperfusion

Therapeutic targets for endometriosis: Genome-wide Mendelian randomization and colocalization analyses

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