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The peroxisome proliferator-activated receptor-γ (PPARγ) improves whole-body insulin sensitivity by regulating the adipogenic and metabolic functions of mature adipocytes. We have previously demonstrated that an active splice variant of X-box binding protein 1 (XBP1s) enhances PPARγ expression during adipogenesis. In this study, we investigated the role of XBP1s, particularly with respect to PPARγ, in the mechanisms underlying insulin sensitivity in mature adipocytes. Insulin was able to stimulate XBP1s generation by activating inositol-requiring enzyme 1 (IRE1) α and was also able to increase its transcriptional activity by inducing nuclear translocation. XBP1s also upregulated the levels of phosphorylated IRS1 and AKT, demonstrating a positive feedback regulatory mechanism linking insulin and XBP1s. XBP1s enhanced the expression of fibroblast growth factor 21 and, in turn, increased PPARγ activity, translocation of GLUT4 to the cell surface, and glucose uptake rate in adipocytes. In addition, XBP1s abolished palmitate-induced insulin resistance in adipocytes by increasing adiponectin secretion, repressing the secretion of proinflammatory adipokines such as leptin, monocyte chemoattractant protein 1, and tumor necrosis factor α, and decreasing fatty acid release. These findings provide a novel mechanism by which XBP1s stimulate insulin sensitivity in adipocytes through fibroblast growth factor 21 induction and PPARγ activation.

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참고문헌 (43건) : 자료제공( 네이버학술정보 )

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번호 참고문헌 국회도서관 소장유무
1 Adipose tissue: between the extremes 네이버 미소장
2 Insulin action and resistance in obesity and type 2 diabetes. 네이버 미소장
3 Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes. 네이버 미소장
4 Cross-Talk between PPARγ and Insulin Signaling and Modulation of Insulin Sensitivity 네이버 미소장
5 Gustafson, B., Hedjazifar, S., Gogg, S., Hammarstedt, A. & Smith, U. Insulin resistance and impaired adipogenesis. Trends Endocrinol. Metab. 26, 193-200 (2015). 미소장
6 Review of the Structural and Dynamic Mechanisms of PPARγ Partial Agonism 네이버 미소장
7 XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor 네이버 미소장
8 X-box binding protein 1 enhances adipogenic differentiation of 3T3-L1 cells through the downregulation of Wnt10b expression 네이버 미소장
9 X‐box binding protein 1 is a novel key regulator of peroxisome proliferator‐activated receptor γ2 네이버 미소장
10 miR-148a is a downstream effector of X-box-binding protein 1 that silences Wnt10b during adipogenesis of 3T3-L1 cells. 소장
11 The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. 네이버 미소장
12 p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. 네이버 미소장
13 The Xbp1s/GalE axis links ER stress to postprandial hepatic metabolism. 네이버 미소장
14 The Role of Adipocyte XBP1 in Metabolic Regulation during Lactation 네이버 미소장
15 Adipocyte Spliced Form of X-Box-Binding Protein 1 Promotes Adiponectin Multimerization and Systemic Glucose Homeostasis 네이버 미소장
16 Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells 네이버 미소장
17 Dissecting Multiple Steps of GLUT4 Trafficking and Identifying the Sites of Insulin Action 네이버 미소장
18 Rapid Activation of Akt2 Is Sufficient to Stimulate GLUT4 Translocation in 3T3-L1 Adipocytes 네이버 미소장
19 Fat and beyond: the diverse biology of PPARgamma. 네이버 미소장
20 PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. 네이버 미소장
21 Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. 네이버 미소장
22 Fibroblast growth factor 21 is regulated by the IRE1α-XBP1 branch of the unfolded protein response and counteracts endoplasmic reticulum stress-induced hepatic steatosis. 네이버 미소장
23 FGF-21 as a novel metabolic regulator. 네이버 미소장
24 Fibroblast Growth Factor-21 Regulates PPARγ Activity and the Antidiabetic Actions of Thiazolidinediones 네이버 미소장
25 FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms 네이버 미소장
26 Defective podocyte insulin signalling through p85-XBP1 promotes ATF6-dependent maladaptive ER-stress response in diabetic nephropathy. 네이버 미소장
27 Prolonged decrease of adipocyte size after rosiglitazone treatment in high- and low-fat-fed rats. 네이버 미소장
28 Saturated fatty acid-induced insulin resistance in rat adipocytes. 네이버 미소장
29 Nguyen, M. T. et al. JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. Biol. Chem. 280, 35361-35371 (2005). 미소장
30 XBP-1, a key regulator of unfolded protein response, activates transcription of IGF1 and Akt phosphorylation in zebrafish embryonic cell line 네이버 미소장
31 IRS1 deficiency protects β-cells against ER stress-induced apoptosis by modulating sXBP-1 stability and protein translation. 네이버 미소장
32 PPARγ signaling and emerging opportunities for improved therapeutics 네이버 미소장
33 Adipose fibroblast growth factor 21 is up-regulated by peroxisome proliferator-activated receptor gamma and altered metabolic states. 네이버 미소장
34 Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5. 네이버 미소장
35 Rosiglitazone treatment increases subcutaneous adipose tissue glucose uptake in parallel with perfusion in patients with type 2 diabetes: a double-blind, randomized study with metformin. 네이버 미소장
36 Thiazolidinediones: effects on insulin resistance and the cardiovascular system. 네이버 미소장
37 FGF21 attenuates lipolysis in human adipocytes – A possible link to improved insulin sensitivity 네이버 미소장
38 Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease. 네이버 미소장
39 Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. 네이버 미소장
40 Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. 네이버 미소장
41 Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone attenuates postincisional pain by regulating macrophage polarization 네이버 미소장
42 Molecular mechanisms that influence the macrophage m1-m2 polarization balance. 네이버 미소장
43 Insulin resistance and its association with catch-up growth in Chinese children born small for gestational age. 네이버 미소장

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