Expression data from Insulin Degrading Enzyme-Knocked Out hepatome human cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE297588 | GEO | 2025/06/04
REPOSITORIES: GEO
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Project description:Insulin degrading enzyme (IDE) is a major enzyme responsible for insulin degradation in the liver. The modulation of insulin degrading enzyme activity is hypothesized to be a link between T2DM and liver cancer. Results provide insight into role of IDE in proliferation and other cell functions. HepG2 cells were transfected with 96nM siRNA for IDE or AllStars Negative Control siRNA (Qiagen) using Lipofectamine 2000 (Invitrogen). 16 h after transfection, cells were treated with 10 nM insulin (Sigma Aldrich) or vehicle for 24 h in serum starvation condition. Total RNA was extracted. For each of the 4 conditions, 3 biological replicates were included.
2014-09-06 | E-GEOD-61142 | biostudies-arrayexpress
Project description:Insulin degrading enzyme (IDE) is a major enzyme responsible for insulin degradation in the liver. The modulation of insulin degrading enzyme activity is hypothesized to be a link between T2DM and liver cancer. Results provide insight into role of IDE in proliferation and other cell functions.
2014-09-06 | GSE61142 | GEO
Project description:Insulin-degrading enzyme is zinc metallo protease degrading low molecular weight substrates including insulin. Ubiquitous expression, high evolutionary conservation, upregulation of Ide in stress situations, and various literature findings suggest a broader function of Ide in cell physiology and protein homeostasis that remains to be elucidated. We used proteomics and transcriptomics approaches searching for leads related to a broader role of Ide in protein homeostasis. We combined an analysis of the proteome and single-cell transcriptome of Ide+/+ and Ide-/- pancreatic islet cells with an examination of the interactome of human cytosolic Ide using proximity biotinylation. We observe an upregulation of pathways related to RNA processing and translation in Ide+/+ relative to Ide-/- islet cells. Corroborating these results and providing a potential mechanistic explanation, proximity biotinylation reveals interaction of Ide with several subunits of CCR4-NOT, a key complex and mRNA deadenylase regulating protein expression "from birth to death". We propose a speculative model in which Ide and CCR4-NOT cooperate to control and limit protein expression in proteotoxic and met-abolic stress situations through cooperation between their deadenylase and protease functions.
2025-06-16 | PXD060228 | Pride
Project description:Appropriate tuning of protein homeostasis through mobilization of the unfolded protein response (UPR) is key to the capacity of pancreatic beta cells to cope with highly variable demand for insulin synthesis. An efficient UPR ensures a sufficient beta cell mass and secretory output but can also affect beta cell resilience to autoimmune aggression. However, the factors regulating protein homeostasis in the face of metabolic and immune challenges are insufficie tly understood. We examined beta cell adaptation to stress in mice deficient for insulin-degrading enzyme (IDE), a ubiquitous protease with high affinity for insulin, a putative ill-defined role in protein homeostasis, and genetic association with type 2 diabetes. IDE deficiency induces a low-level UPR in both standard and autoimmune non-obese diabetic (NOD) mice, associated with rapamycin-sensitive beta cell proliferation, as well as protection from diabetes in NOD mice. Moreover, in NOD islets, IDE deficiency specifically induces strong upregulation of regenerating islet-derived protein 2, a protein attenuating inflammation and protecting from autoimmunity. Our findings establish a role of IDE in islet cell protein homeostasis, corroborate the link between low-level UPR and proliferation, and identify an anti-inflammatory islet cell response uncovered in the absence of IDE of potential interest in autoimmune diabetes.
2024-06-16 | PXD034826 | Pride
Project description:Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa-/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa-/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa-/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD. Gene expression in cerebral cortex and cerebellum of mice were determined using Agilent chips. To ensure higher quality results in gene expression data, we conducted microarrays on 4 mice per group. Young mice were 2 months old and the other aged mice were 29 months old at the time of use. Data were standardized using global normalization and pro-cessed by R-program. An absolute fold change threshold of greater than 1.5 was required to be considered for further analyses. Expression values were in log2 scale.
2015-11-20 | E-GEOD-75047 | biostudies-arrayexpress
Project description:Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa-/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa-/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa-/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD.
2015-11-20 | GSE75047 | GEO
Project description:Basic helix loop helix enhancer 40 (Bhlhe40) is a transcription factor expressed in rodent hippocampus, however, its role in neuronal function is not well understood. Here, we used Bhlhe40 null mice on a congenic C57Bl6/J background (Bhlhe40 KO) to investigate the impact of Bhlhe40 on neuronal excitability and synaptic plasticity. A whole genome expression array predicted that Bhlhe40 KO mice have up-regulated insulin-related pathways and down-regulated neuronal signaling-related pathways in the hippocampus. We validated that insulin degrading enzyme mRNA (Ide) and IDE protein are significantly downregulated in Bhlhe40 KO hippocampi. No significant difference was observed in hippocampal insulin levels. In hippocampal slices, we found CA1 neurons have increased miniature excitatory post-synaptic current (mEPSC) amplitude and decreased inhibitory post-synaptic current (IPSC) amplitude, indicating hyper-excitability in CA1 neurons in Bhlhe40 KO mice. At CA1 synapses, we found a reduction in long term potentiation (LTP) and long term depression (LTD), indicating an impairment in hippocampal synaptic plasticity in Bhlhe40 KO hippocampal slices. Bhlhe40 KO mice displayed no difference in seizure response to the convulsant kainic acid (KA) relative to controls. We found that while Bhlhe40 KO mice have decreased exploratory behavior they do not display alterations in spatial learning and memory. Together this suggests that Bhlhe40 plays a role in modulating neuronal excitability and synaptic plasticity ex vivo, however, Bhlhe40 alone does not play a significant role in seizure susceptibility and learning and memory in vivo. In addition, based on the reduction in IDE protein levels in these mice, there may be dysregulation of other known IDE substrates, namely insulin growth factor (Igf)-1, Igf-2, and Amyloid beta (Aβ).
2018-05-03 | GSE85959 | GEO
Project description:Expression data from Insulin Degrading Enzyme-Knocked Out hepatome human cells
| PRJNA1265225 | ENA
Project description:Purpose: The function of Prom1, a penta-transmembrane glycoprotein which is a used as cancer stem cell marker, in the liver is unclear. The goal of this study is to examine the effect of Prom1 -/- in mouse primary hepatocyte transcriptomes. Prominin-1 (Prom1) is a major cell surface marker of cancer stem cells, but its physiological functions in the liver have not been elucidated. We analyzed the levels of mRNA transcripts in serum-starved primary Prom1+/+ and Prom1-/- mouse hepatocytes using RNA-sequencing (RNA-seq) data, and found that CREB target genes were down-regulated. This initial observation led us to determine that the Prom1 deficiency inhibited cAMP response element binding protein (CREB) activation and gluconeogenesis, but not cyclic AMP (cAMP) accumulation, in glucagon-, epinephrine-, or forskolin-treated liver tissues and primary hepatocytes, and mitigated glucagon-induced hyperglycemia. Because Prom1 interacted with radixin, the Prom1 deficiency prevented radixin from localizing to the plasma membrane. Moreover, systemic adenoviral knockdown of radixin inhibited CREB activation and gluconeogenesis in glucagon-treated liver tissues and primary hepatocytes, and mitigated glucagon-elicited hyperglycemia. Based on these results, we conclude that Prom1 regulates hepatic PKA signaling via radixin functioning as an A kinase-anchored protein (AKAP).
2020-01-22 | GSE144018 | GEO
Project description:Glucagon has recently been found to modulate liver fat content, in addition to its role in regulating gluconeogenesis. However, the precise mechanisms by which glucagon signaling synchronizes glucose and lipid metabolism in the liver remain poorly understood. By employing chemical and genetic approaches, we demonstrate that inhibiting the androgen receptor (AR) impairs the ability of glucagon to stimulate gluconeogenesis and lipid catabolism in primary hepatocytes and female mice. Notably, AR expression in the liver of female mice is up to three times higher than that in their male littermates, accounting for the more pronounced response to glucagon in females. Mechanistically, hepatic AR promotes energy metabolism and enhances lipid breakdown for liver glucose production in response to glucagon treatment through the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)/estrogen-related receptor alpha (ERRα)-mitochondria axis. Overall, our findings highlight the crucial role of hepatic AR in mediating glucagon signaling and the sexual dimorphism in hepatic glucagon sensitivity.
2025-01-01 | GSE236551 | GEO