Insig2 antibody
- Known as:
- Insig2 (anti-)
- Catalog number:
- orb101125
- Product Quantity:
- EUR
- Category:
- -
- Supplier:
- Biorbyt biorb
- Gene target:
- Insig2 antibody
Related genes to: Insig2 antibody
- Gene:
- INSIG2 NIH gene
- Name:
- insulin induced gene 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 2q14.1-q14.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-02-17
- Date modifiied:
- 2018-02-13
Related products to: Insig2 antibody
Related articles to: Insig2 antibody
- The sterol response element binding proteins (SREBPs), SREBP-1a/c and SREBP-2, are sterol-regulated transcription factors that control the expression of cholesterol and fatty acid-raising genes. Elevated expression of SREBPs has been linked to increased morbidity and mortality rates associated with conditions including obesity, cancer, and cardiovascular disease. Therefore, the development of new therapeutics to inhibit SREBP activity may be beneficial for treating various diseases associated with altered lipid levels. In their inactive state, SREBPs remain sequestered in the ER membrane in a complex with SREBP cleavage activating protein (SCAP) and one of two ER-anchoring proteins, Insig-1 or Insig-2. Activation proceeds through dissociation of SREBP/SCAP from Insigs, SCAP-assisted translocation to the Golgi, proteolytic membrane release and nuclear import. We employed a high-throughput enzyme complementation assay to identify inhibitors of SREBP-2 translocation to the nucleus, resulting in the identification of VB-84922 having an IC value of 0.45 ± 0.052 μM. VB-84922-mediated inhibition of nuclear translocation was confirmed by fluorescence microscopy with an mNeonGreen-SREBP-2 fusion protein. Crucially, VB-84922 inhibited the lovastatin-induced activity of an SREBP-responsive reporter construct and suppressed the expression of endogenous SREBP target genes. Co-transfection assays using an SREBP reporter and fluorescence microscopy were used to delineate the target of VB-84922 in the SREBP activation pathway. The drug blocked ER export of wild-type SCAP but had no effect on SREBP activity in cells expressing the nuclear form of SREBP-1a, or mutated versions of SCAP that are unable to bind Insigs and that chaperone SREBP to the Golgi constitutively. These results suggest that VB-84922 targets a step upstream of ER export in the SREBP activation cascade. VB-87496, a therapeutic lead compound, developed from VB-84922, demonstrated efficacy within a murine acute fasting-refeeding model by inhibiting full-length SREBP protein maturation and SREBP-dependent transcription. VB-87496 represents a specific SREBPs-SCAP inhibitor that has potential for further lead optimization medicinal chemistry efforts to generate a potent and selective pre-clinical candidate for treating lipid-related diseases. - Source: PubMed
Publication date: 2026/03/24
Corbalan J JoseSchormann WiebkeJagadeesan PranaviKale JustinHuang Yu-ChiangSiegel RachaelBeasley James RTung Jyun-PengNohturfft AxelAndrews DavidNickels Joseph T - Metabolic dysfunction-associated steatotic liver disease (MASLD) ranges from simple steatosis (MASL) to fibrotic steatohepatitis (MASH). Yet, the molecular mechanisms initiating these divergent outcomes remain unclear. We addressed the question whether MASLD induced by a high-sucrose/starch diet (MCS) is similar to a high-fat, methionine- and choline-deficient diet (MCD+HFD). To investigate early genomic programming events in these MASLD models, we fed C57BL/6N mice either an MCS or MCD+HFD for 14 days. Histopathology and serum biochemistries confirmed MASLD phenotypes and transcriptomics guided pathway enrichment analysis. Furthermore, ChIP-seq-validated transcription factor targets enabled construction of regulatory gene networks (RGNs) in glucose homeostasis and lipid metabolism. Importantly, the MCS and MCD+HFD caused 692 and 703 differentially expressed genes, and although transcriptomics revealed shared genomic responses, we also observed diet-specific adaptations. Both diets repressed glycolysis, yet MCS showed broader suppression. Furthermore, fatty acid β-oxidation and lipid droplet biogenesis was induced whereas lipogenesis, cholesterol biosynthesis and the kynurenine pathway were repressed. Strikingly, the high-sucrose/high-starch diet suppressed acute-phase, prostaglandin, redox, antigen presentation, and autophagy pathways. Conversely, the high-fat MCD-diet activated cytokine signaling, macrophage networks, and inflammatory programs. Intriguingly, RGNs aided an identification of diet-specific master regulatory networks with MCS stimulating Insig2, Id1, and Mafb signaling. Conversely, the high-fat MCD-diet silenced Srebf1, Scd1, and Acly. Together, our findings highlight early genomic reprogramming events in MASLD, and unlike the high-fat MCD-diet which stimulates MASH, we report high-sucrose/high-starch to elicit benign steatosis without inflammation. - Source: PubMed
Publication date: 2026/03/20
Xu YanzheZhu YunLee KyuhongBorlak Jürgen - : Lycopene (LYC) is a carotenoid obtained primarily from tomatoes and tomato-based products. LYC displays potent antioxidant properties and its intake and circulating concentrations have been associated with a reduced risk of prostate and breast cancers as well as cardiovascular diseases. Following absorption, it is mainly stored in adipose tissue, which accounts for approximately two-thirds of total body stores, where it may influence processes such as oxidative stress and inflammation. However, the factors determining LYC concentration in adipose tissue remain poorly understood. This study aimed to characterize the interindividual variability of adipose tissue LYC concentration and identify single nucleotide polymorphisms (SNPs) associated with it. : Forty-three healthy adult males (mean age: 32.0 ± 2.0 year; mean BMI: 23.0 ± 0.3 kg m) underwent whole-genome genotyping. Periumbilical adipose tissue samples were collected on six occasions (in the fasting state and 8 h after consumption of three different standardized meals), and plasma and adipose tissue LYC concentrations were quantified by HPLC. Forty-three candidate genes potentially involved in LYC metabolism were selected, and the association of 3786 SNPs from these genes with adipose tissue LYC concentration was assessed using partial least squares regression. : Adipose tissue LYC concentration showed marked interindividual variability (CV = 55%). Adipose tissue and fasting plasma LYC concentrations were significantly, but moderately, correlated (Pearson's = 0.37; 95% CI: 0.07-0.61). An internally validated PLS regression model consisting of 17 SNPs in 11 genes-, , , , , , , , , , and -explained 55% of the variability in adipose tissue LYC concentration (adjusted ). : Adipose tissue LYC concentration displays high interindividual variability, which can be explained in part by genetic variants in genes involved in carotenoid and lipid metabolism. : ClinicalTrials.gov registration number NCT02100774. - Source: PubMed
Publication date: 2026/04/14
Zumaraga Mark PretzelBorel PatrickDesmarchelier Charles - Aerobic glycolysis supports tumor growth, but how tumor cells sense glucose to coordinate biosynthesis remains largely unclear. Here we show that in hepatocellular carcinoma cells, glucose-activated PKCε phosphorylates the purine synthesis enzyme ADSL, triggering its translocation to the endoplasmic reticulum. ADSL then promotes succination of INSIG1/2, which disrupts the interaction between INSIG proteins and SCAP, leading to the translocation of the SCAP-SREBP complex to the Golgi, the activation of SREBP-1 and the transcription of downstream lipogenesis-related genes, proliferation of tumor cells, and tumorigenesis in mice. Through virtual screening, we identify Elsulfavirine, an approved HIV drug, which blocks ADSL-INSIG interaction and suppresses SREBP-1 activation induced by glucose. Combining Elsulfavirine with Lenvatinib synergistically inhibits tumor growth. Clinically, ADSL phosphorylation and INSIG succination correlate with SREBP-1 activation and poor prognosis in human HCC. In summary, these findings reveal a repurposing mechanism by which tumor cells coordinate glucose metabolism and lipogenesis via a moonlighting function of ADSL and underscore a repurposing strategy for liver cancer therapy. - Source: PubMed
Publication date: 2026/03/15
Duan YuranWang ShuoLiu JianyuQin WenxingShen YuliHou YueruSun XueLin YanniHu ZhiqiangDong BofeiBi YanliYang HuangLi MinXiao LiweiWu QingangBai XueliWang YuhaoLi GaopengDing YuanMao ZhengweiLuo YangLu ZhiminLiu TongXu DaqianLiu ShijianZhan PengWang Zheng - Metabolic side effects represent a major long-term concern in antipsychotic (AP)-treated early psychosis. We evaluated the weight gain and changes in related metabolic parameters in patients followed up for 12 months. We also explored DNA methylation of four genes associated with weight gain (ADRA2A, INSIG2, LEP, MC4R). We included patients aged 15-64 years followed in the Ribeirão Preto Early Intervention in Psychosis Program from two different cohorts (Clinical sample, n = 147; Epigenetic sample, n = 59). DNA methylation was analysed by pyrosequencing only at baseline, after several weeks of AP exposure. In both cohorts, 40% of patients initially received second-generation antipsychotics (SGAs), increasing to over 70% after one year. Clinical sample: At follow-up, patients exhibited significant increases in body mass index (p < 0.001), triglycerides (p < 0.001), HDL-c (p = 0.001) and LDL-c (p < 0.001). Patients predominantly on SGAs during the 12 months had almost three times higher chance of weight gain than those using haloperidol. Other factors associated with weight gain included non-white skin colour (OR = 2.6), fewer years of schooling (OR = 2.5) and a weight gain of at least 7% at three months (OR = 3.1). Epigenetic sample: Patients receiving SGA treatment (median = 23.4 weeks) at baseline showed hypermethylation within the MC4R promoter region in relation to patients using haloperidol (median = 18.6 weeks). No changes in the baseline methylation of other genes related to weight gain or AP drugs were observed longitudinally. MC4R promoter hypermethylation in SGA-treated patients suggests drug-induced metabolic alterations and a potential role of MC4R as a biomarker for predicting AP-related metabolic risk. - Source: PubMed
Publication date: 2026/02/24
Loureiro C MFachim H ABissoli G CCorsi-Zuelli FShuhama RMenezes P RLouzada-Junior PDalton C FReynolds G PDel-Ben C M