Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0019209 (
hepatomegaly
)
5,798
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In the liver, insulin controls both lipid and glucose metabolism through its cell surface receptor and intracellular mediators such as
phosphatidylinositol 3-kinase
and serine-threonine kinase AKT. The insulin signaling pathway is further modulated by protein tyrosine phosphatase or lipid phosphatase. Here, we investigated the function of phosphatase and tension homologue deleted on chromosome 10 (PTEN), a negative regulator of the
phosphatidylinositol 3-kinase
/AKT pathway, by targeted deletion of Pten in murine liver. Deletion of Pten in the liver resulted in increased fatty acid synthesis, accompanied by
hepatomegaly
and fatty liver phenotype. Interestingly, Pten liver-specific deletion causes enhanced liver insulin action with improved systemic glucose tolerance. Thus, deletion of Pten in the liver may provide a valuable model that permits the study of the metabolic actions of insulin signaling in the liver, and PTEN may be a promising target for therapeutic intervention for type 2 diabetes.
...
PMID:Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. 1476 18
The role of proteomic instability in cancer, particularly amyloidogenesis, remains obscure. Heat shock factor 1 (HSF1) transcriptionally governs the proteotoxic stress response to suppress proteomic instability and enhance survival. Paradoxically, HSF1 promotes oncogenesis. Here, we report that AKT activates HSF1 via Ser
230
phosphorylation. In vivo, HSF1 enables megalencephaly and
hepatomegaly
, which are driven by hyperactive
phosphatidylinositol 3-kinase
/AKT signaling.
Hsf1
deficiency exacerbates amyloidogenesis and elicits apoptosis, thereby countering tissue overgrowth. Unexpectedly, HSF1 physically neutralizes soluble amyloid oligomers (AOs). Beyond impeding amyloidogenesis, HSF1 shields HSP60 from direct assault by AOs, averting HSP60 destabilization, collapse of the mitochondrial proteome, and, ultimately, mitophagy and apoptosis. The very same mechanism occurs in Alzheimer's disease. These findings suggest that amyloidogenesis may be a checkpoint mechanism that constrains uncontrolled growth and safeguards tissue homeostasis, congruent with its emerging tumor-suppressive function. HSF1, by acting as an anti-amyloid factor, promotes overgrowth syndromes and cancer but may suppress neurodegenerative disorders.
...
PMID:HSF1 physically neutralizes amyloid oligomers to empower overgrowth and bestow neuroprotection. 3317 89
