PPARγ transcriptionally regulates the expression of insulin-degrading enzyme in primary neurons

Du, Jing; Zhang, Lang; Liu, Shubo; Zhang, Chi; Huang, Xiuqing; Li, Jian; Zhao, Nanming; Zhao, Wei

doi:10.1016/j.bbrc.2009.04.047

Cited by 58 publications

(64 citation statements)

References 22 publications

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“…The link described here among mitochondrial biogenesis, IDE promoter activation, and L-IDE expression supports a concerted action of NRF-1 together with PPAR␥ (co-activated by PGC-1␣) (21) to enhance hIDE transcription. The role of PCG-1␣ in gluconeogenesis and insulin resistance (54); the relevance of the insulin-PI3K-akt pathway in PPAR␥ (21), NRF-1 activity (55), and IDE expression (56); and the metabolic phenotype of insulin resistance described in AD and diabetes mellitus patients confirm the relevance of our results in understanding the role of hIDE in the pathogenesis of both human diseases (Fig.…”

Section: Discussionsupporting

confidence: 70%

“…The molecular mechanisms that govern the promoter activity of hPreP and hIDE-Met 1 are still unknown. However, recent reports showed that the hIDE promoter may be a direct target of PPAR␥ (21), HES-1/Hey-1 (key downstream targets of Notch signaling) (15), and NRF-1 (22). NRF-1 interacts with peroxisome proliferator-activated receptor ␥ coactivator 1 (PGC-1) family proteins (23) to induce mitochondrial biogenesis.…”

mentioning

confidence: 99%

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Transcriptional Regulation of Insulin-degrading Enzyme Modulates Mitochondrial Amyloid β (Aβ) Peptide Catabolism and Functionality

Leal

Magnani

Villordo

et al. 2013

Journal of Biological Chemistry

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Background: Mitochondrial accumulation of amyloid ␤ (A␤) promotes organelle dysfunction and Alzheimer disease (AD) neuropathology. Results: IDE-Met 1 localizes in mitochondria, is present in brain, and is regulated by the master regulator of mitochondrial biogenesis. Conclusion: Mitochondrial biogenesis controls mitochondrial A␤ levels.Significance: This study identifies a molecular mechanism that links mitochondrial biogenesis with A␤ degradation, suggesting that deregulation of this pathway could induce A␤-mediated mitochondrial dysfunction.

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Section: Discussionsupporting

confidence: 70%

mentioning

confidence: 99%

Transcriptional Regulation of Insulin-degrading Enzyme Modulates Mitochondrial Amyloid β (Aβ) Peptide Catabolism and Functionality

Leal

Magnani

Villordo

et al. 2013

Journal of Biological Chemistry

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“…Several pathways can regulate IDE levels in different experimental systems. The PI3K pathway (46), insulin receptor signaling (47), the transcription factor peroxisome proliferator-activated receptor -␥ (48,49), palmitic acid, docosahexaenoic acid (50), as well as up-regulation of exosome secretion dependent on protein isoprenylation (30) have been implicated. Future work will investigate the activation of these pathways by BRI2.…”

Section: Discussionmentioning

confidence: 99%

BRI2 Protein Regulates β-Amyloid Degradation by Increasing Levels of Secreted Insulin-degrading Enzyme (IDE)

Kilger

Buehler

Woelfing

et al. 2011

Journal of Biological Chemistry

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Background:The British precursor protein (BRI2) influences amyloid precursor protein metabolism. Results: BRI2 lowers ␤-amyloid peptide levels by increasing levels of secreted insulin-degrading enzyme (IDE) in both cells and mice. Conclusion: BRI2 as a receptor protein regulates IDE levels and in turn promotes ␤-amyloid degradation. Significance: Targeting the regulation of IDE may lead to new approaches to therapeutically address sporadic Alzheimer disease.

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“…In addition to insulin, IDE catalyzes the degradation of β-amyloid; IDE dysfunction is a critical factor in the pathogenesis of Alzheimer disease. In various studies on Alzheimer disease, researchers have discovered that the IDE gene promoter contains a peroxisome proliferatoractivated receptor-γ (PPAR-γ) binding site, and PPAR-γ induces IDE gene transcription in neuronal cells [32] . Furthermore, IDE gene transcription is induced by nuclear respiratory factor 1 (NRF1) [33] and is reduced in neuronal cells by the Notch signaling proteins HES-1 and Hey-1 [34] .…”

Section: Discussionmentioning

confidence: 99%

Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice

et al. 2015

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Aim: Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. In this study, we investigated the effects of EGCG on insulin resistance and insulin clearance in non-alcoholic fatty liver disease (NAFLD) mice. Methods: Mice were fed on a high-fat diet for 24 weeks. During the last 4 weeks, the mice were injected with EGCG (10, 20 and 40 mg·kg -1 ·d -1 , ip). Glucose tolerance, insulin tolerance and insulin clearance were assessed. After the mice were euthanized, blood samples and tissue specimens were collected. Glucose-stimulated insulin secretion was examined in isolated pancreatic islets. The progression of NAFLD was evaluated histologically and by measuring lipid contents. Insulin-degrading enzyme (IDE) protein expression and enzyme activity were detected using Western blot and immunocapture activity assays, respectively. Results: The high-fat diet significantly increased the body weight and induced grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning) accompanied by severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in the model mice. Administration of EGCG dose-dependently ameliorated the hepatic morphology and function, reduced the body weight, and alleviated hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in NAFLD mice. Furthermore, EGCG dosedependently enhanced insulin clearance and upregulated IDE protein expression and enzyme activity in the liver of NAFLD mice. Conclusion: EGCG dose-dependently improves insulin resistance in NAFLD mice not only by reducing body weight but also through enhancing the insulin clearance by hepatic IDE. The results suggest that IDE be a potential drug target for the treatment of NAFLD.

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PPARγ transcriptionally regulates the expression of insulin-degrading enzyme in primary neurons

Cited by 58 publications

References 22 publications

Transcriptional Regulation of Insulin-degrading Enzyme Modulates Mitochondrial Amyloid β (Aβ) Peptide Catabolism and Functionality

Transcriptional Regulation of Insulin-degrading Enzyme Modulates Mitochondrial Amyloid β (Aβ) Peptide Catabolism and Functionality

BRI2 Protein Regulates β-Amyloid Degradation by Increasing Levels of Secreted Insulin-degrading Enzyme (IDE)

Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice

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