GLUT4 _ SLC2A4
- Known as:
- GLUT4 _ SLC2A4
- Catalog number:
- BB-PA1039
- Product Quantity:
- 100 µg
- Category:
- -
- Supplier:
- ACR
- Gene target:
- GLUT4 _ SLC2A4
Related genes to: GLUT4 _ SLC2A4
- Gene:
- SLC2A4 NIH gene
- Name:
- solute carrier family 2 member 4
- Previous symbol:
- GLUT4
- Synonyms:
- -
- Chromosome:
- 17p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1989-03-06
- Date modifiied:
- 2016-10-05
Related products to: GLUT4 _ SLC2A4
Related articles to: GLUT4 _ SLC2A4
- Pelvic floor dysfunction (PFD) is a common disease in women that seriously affects physical and psychological health. Menopause-associated estrogen reduction is one of the risk factors. However, the role and mechanism of estrogen in PFD remains unclear. In this study, we observed atrophy of both fast and slow muscle fibers in the pelvic floor muscle (PFM) of ovariectomized rats, accompanied by decreased expression of estrogen receptor α (ERα). Estrogen deficiency severely impaired the proliferation, differentiation, and mitochondrial function of C2C12 myoblasts and increased apoptosis, which could be rescued by ERα agonist. Mechanistically, estrogen deficiency led to the downregulation of ERα, which in turn suppressed the expression of glucose transporter 4 (GLUT4) and its trafficking regulator Rac family small GTPase 1 (RAC1). This disruption abolished the critical co-localization of GLUT4 with RAC1, resulting in defective glucose uptake, mitochondrial dysfunction, and ultimately impaired myoblast proliferation and differentiation. Both ERα activation and GLUT4 overexpression rescued these defects. Thus, our study delineates a novel ERα/GLUT4 pathway that mediates PFM atrophy under estrogen deficiency conditions, providing a potential therapeutic target for PFD. - Source: PubMed
Publication date: 2026/05/14
Huang XiaoyuZhou MengqiWang YingChen MaoXiao YaLi LingyunZhu FangyiChen LiyingTian XiaoyuWu ShimanLi BingshuHong Li - Aerobic exercise improves systemic insulin sensitivity by modulating muscle glucose metabolism. The CHRONO/BMAL1 pathway constitutes a core component of the endogenous molecular clock and participates in glucose metabolic regulation; however, whether it mediates exercise-induced metabolic benefits under high-fat diet (HFD) conditions remains unclear. We therefore investigated the role of this pathway in conferring protective effects of aerobic exercise against HFD-induced glucose metabolic dysfunction in skeletal muscle, by subjecting wild-type (WT) and inducible muscle-specific Chrono overexpression (Chrono IMOE) mice to an HFD with or without 12-week exercise. Unlike in WT mice, exercise failed to ameliorate adipose mass, dyslipidemia, and insulin resistance in HFD-fed Chrono IMOE mice. Mechanistically, in skeletal muscle of Chrono IMOE mice, Chrono overexpression suppressed exercise-induced reductions in CHRONO expression and CHRONO-BMAL1 binding, as well as the increase in BMAL1 levels. Consequently, despite elevated p-TBC1D1 and GLUT4 expression, exercise failed to promote GLUT4 sarcolemmal colocalization or upregulate gene expression of key enzymes for glycolysis and glycogen metabolism in skeletal muscle of Chrono IMOE mice. These findings demonstrate that preventing CHRONO‑BMAL1 dissociation via muscle-specific Chrono overexpression abrogates exercise-induced GLUT4 membrane trafficking, transcriptional activation of glycolytic/glycogen metabolic genes, and systemic insulin sensitivity improvements in HFD-fed mice, establishing CHRONO‑BMAL1 dissociation as a required step for these exercise adaptations. - Source: PubMed
Publication date: 2026/05/14
Xu LeiJia JieYan LuWang YangwenjieMiao ShudanZhang Ying - High-fat diets (HFDs) are a key contributor to obesity and promote oxidative stress and inflammation, which are associated with muscle atrophy and insulin resistance (IR). Passiflora edulis exhibits anti-obesity, antioxidant, and anti-inflammatory effects. The study aimed to investigate the potential benefit of P. edulis f. flavicarpa (PF) extract in preventing obesity-associated muscle atrophy and IR. The PF extract effectively inhibited cholesterol micelle solubility with an IC of 3431 µg/mL and decreased fat accumulation in 3T3-L1 adipocytes. Furthermore, this study investigated a model of HFD-induced IR and muscle atrophy in rats. Thirty-five male Sprague-Dawley (SD) rats were induced with obesity by HFD and were administered 250 and 500 mg/kg/day of PF extract. Rats fed with an HFD were associated with fat accumulation and oxidative stress, which promoted inflammation, muscle damage, muscle atrophy, and IR in obese rats. However, administration of PF extract effectively mitigated these effects. The PF extract decreased fat accumulation in white adipose tissues and gastrocnemius (GAS) muscle by inhibiting fat absorption and synthesis, particularly Cd36 and Hmgcr. The PF extract also notably reduced oxidative stress-induced muscle inflammation and damage via elevating nuclear factor erythroid 2-related factor 2 (Nrf2) and reducing nuclear factor kappa B (NF-κB) expressions. Additionally, PF extract was found to mechanistically prevent muscle atrophy by inhibiting Fbxo32, Trim63, and B-cell lymphoma 2 (BCL2)-associated X (Bax) expressions, while enhancing Bcl2 expression. We also found that PF extract mitigated muscle IR by upregulation of the insulin receptor substrate-1/phosphatidylinositol-3 kinase/protein kinase B (IRS-1/PI3K/AKT) pathway and Slc2a4 expression. The findings indicate that PF extract can prevent skeletal muscle loss and IR in obesity by modulating oxidative stress, inflammation, and activating IRS-1/PI3K/AKT signaling pathway. - Source: PubMed
Chobsuay NraratChonpathompikunlert PennapaSrivilai JukkarinMalakul WachirawadeeLimpeanchob NanteetipAimjongjun SathidTunsophon Sakara - Glucose transporter type 4 (GLUT4), encoded by the gene, is the final effector of insulin-stimulated glucose uptake in insulin-sensitive tissues: skeletal muscle, adipose tissue, and cardiac muscle. Its dynamic localization, retained intracellularly under basal conditions and extensively translocated to the plasma membrane upon stimulation, makes it a master regulator of glycemic homeostasis. While the canonical insulin pathway (PI3K/Akt/TBC1D4) is the most potent and specific mechanism in the postprandial state, its dysfunction is centrally associated with insulin resistance and type 2 diabetes mellitus (T2DM). Crucially, robust alternative signaling networks function completely independently of insulin to regulate GLUT4 synthesis and translocation. Prominent among these are contraction-mediated pathways in skeletal muscle, which employ calcium signaling (via CaMKII), mechanical/metabolic stress sensors (via p38 MAPK γ/δ), and AMP-activated protein kinase (AMPK). This review critically integrates current knowledge, linking the molecular architecture and post-translational modifications of GLUT4 to the complex, tissue-specific signaling networks that govern its vesicular trafficking. We emphasize the hierarchy, redundancy, and interdependence of these pathways, highlighting differences between acute translocation and chronic transcriptional adaptations. Finally, we discuss how deciphering insulin-independent mechanisms offers promising therapeutic opportunities, particularly in identifying pharmacological targets that mimic the metabolic benefits of physical exercise. - Source: PubMed
Publication date: 2026/04/13
Ramos-Jiménez ArnulfoRubio-Valles MariazelGuereca-Arvizuo JaimeJuárez-Oropeza Marco ARamos-Hernández Javier AChávez-Guevara Isaac AGonzález-Rodríguez EverardoMoreno-Brito VerónicaHernández Torres Rosa P - NEGR1 (neuronal growth regulator 1) has been genetically linked to metabolic and neuropsychiatric disorders; however, its cellular function in insulin-responsive tissues remains poorly understood. Here, we investigated the role of NEGR1 in regulating actin cytoskeletal dynamics and insulin-stimulated GLUT4 trafficking in skeletal muscle. We found that loss of reduced GLUT4 abundance selectively in predominantly glycolytic skeletal muscles in vivo. Despite preserved insulin-induced Akt phosphorylation, insulin-stimulated GLUT4 translocation was markedly impaired in both Negr1-deficient and NEGR1-overexpressing muscle cells. Mechanistically, deficiency was associated with enhanced PAK-cofilin signaling and excessive intracellular F-actin accumulation that likely impedes GLUT4 vesicle trafficking. In contrast, NEGR1 overexpression did not increase total F-actin content but induced abnormal peripheral actin organization, resulting in constitutive GLUT4 surface localization and elevated basal glucose uptake. Consistent with these findings, both loss and overexpression of NEGR1 disrupted insulin-induced Rac1-dependent actin remodeling without affecting Akt signaling. Collectively, these results identify NEGR1 as a critical modulator of actin homeostasis required for proper insulin-stimulated GLUT4 trafficking and glucose uptake in skeletal muscle, providing mechanistic insight into the metabolic abnormalities associated with NEGR1 dysregulation. Neuronal growth regulator 1 (NEGR1) regulates actin cytoskeletal homeostasis required for insulin-stimulated GLUT4 trafficking in skeletal muscle. NEGR1 dysregulation alters PAK-cofilin signaling, induces aberrant F-actin organization, and impairs GLUT4 vesicle movement independent of Akt signaling. Because NEGR1 is a major genetic risk factor for major depressive disorder, these findings reveal a shared actin-based mechanism linking metabolic dysfunction and neuropsychiatric disease. - Source: PubMed
Publication date: 2026/03/28
Yun Seo-YoungLee Soojin