Ask about this productRelated genes to: INSIG1 Blocking Peptide
- Gene:
- INSIG1 NIH gene
- Name:
- insulin induced gene 1
- Previous symbol:
- -
- Synonyms:
- CL-6, MGC1405
- Chromosome:
- 7q36.3
- Locus Type:
- gene with protein product
- Date approved:
- 1997-05-15
- Date modifiied:
- 2016-10-05
Related products to: INSIG1 Blocking Peptide
Related articles to: INSIG1 Blocking Peptide
- This study aimed to investigate whether mixed heavy metal exposure (lead, cadmium, manganese, and arsenic) during pregnancy induces gestational diabetes mellitus (GDM)-like phenotypes and to explore the associated molecular alterations. We examined the effects of exposure on metabolic disturbances using a Sprague-Dawley rat model exposed to low- and high-dose mixed heavy metals, with doses selected based on biomonitoring data. The results showed that high-dose mixed heavy metal exposure significantly increased blood glucose levels in rats, elevated the area under the curve (AUC) during the oral glucose tolerance test (OGTT), and induced insulin resistance and dyslipidemia. Concurrently, pathological examinations revealed hepatocyte steatosis, inflammatory cell infiltration, and mitochondrial abnormalities in liver tissues. Transcriptomic and metabolomic analyses identified significant disruption of the glycerophospholipid metabolic pathway following heavy metal exposure, suggesting the involvement of this pathway in the observed metabolic disturbances. Lasso regression analysis identified Insig1 as a candidate gene associated with lipid metabolic alterations, a finding subsequently validated by qPCR. Overall, mixed heavy metal exposure during pregnancy was associated with GDM-like metabolic abnormalities in rats. Disruption of glycerophospholipid metabolism and altered Insig1 expression likely contribute to these effects, providing molecular evidence linking mixed heavy metal exposure to gestational metabolic dysfunction. - Source: PubMed
Publication date: 2026/04/21
Sun TianaoZheng ZhanyueMa YongjiePan MinglianZhou YingjieWei JingxiaYuan XinyuWan JinhaoLi YouSun Yan - The stems and leaves of (CPSL) are commonly treated as agricultural waste, yet they are rich in antioxidants and other bioactive compounds. In order to explore their applicability in livestock feeding, a systematic evaluation was conducted on the dose-dependent effects of CPSL on yak production traits and meat characteristics. A total of forty yaks were randomly allocated into four experimental groups, including a control group fed a basal diet and three treatment groups receiving the basal diet supplemented with 0.5%, 1.0%, or 2.0% CPSL. Results indicated that the 2.0% CPSL supplementation group exhibited the highest net meat yield while significantly improving meat processing suitability. Through transcriptomic profiling, 13 genes were found to be differentially expressed between the control and CPSL-treated groups, with functions related to myofiber formation and energy metabolic processes. A marked upregulation of insulin-sensitizing gene 1 (INSIG1) and arginase 2 (ARG2) was observed specifically in the group receiving the intermediate CPSL dose. Metabolomic profiling further revealed that 81 shared differentially abundant metabolites were primarily involved in the AMPK signaling and oxidative phosphorylation pathways. Collectively, CPSL not only fortifies yak beef production by optimizing growth and slaughter performance but also significantly enhances meat tenderness and processing adaptability through regulating core mechanisms governing redox hubs and energy metabolism. These findings offer novel insights into the high-value utilization of CPSL as a feed additive. - Source: PubMed
Publication date: 2026/04/03
Yang XueLi YihengShen RuhengDuan YufengSong RendeShi HongmeiKong XiangyingHua YongliZhang WangangZhang Li - 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 - Acetyl-CoA synthetase 2 (ACSS2) is the obligatory gatekeeper for converting rumen-derived acetate into acetyl-CoA in ruminants. However, whether ACSS2 actively regulates the transcriptional networks governing lactation, beyond its catalytic role, remains unclear. This study aimed to elucidate the molecular characteristics of buffalo ACSS2 and investigate its function as a central node in the metabolic-transcriptional circuitry of buffalo mammary epithelial cells (BuMECs). - Source: PubMed
Publication date: 2026/03/11
Huang LigeWang RongpingZhou FangtingGao RuixiaFan XinyangMiao Yongwang - 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