title: Regulation of the acid-labile subunit in sustained endotoxemia.
abstract: The effect of sustained endotoxemia on expression of the acid-labile subunit (ALS) in relation to hepatic markers of altered GH and insulin sensitivity was examined. Juvenile rats were injected with endotoxin twice daily for 48 h, causing reduced food intake and attenuated growth. In pair-fed controls, food restriction caused marked suppression of ALS gene expression and circulating levels within 12 h, and endotoxemia augmented this effect. This acute effect of endotoxin corresponded temporally with transient induction of suppressor of cytokine signaling (SOCS)-3, cytokine-inducible SH2-containing protein (CIS), phosphoenolpyruvate carboxykinase (PEPCK), and insulin-like growth factor-binding protein (IGFBP)-1 and suppression of GH receptor (GHR). During the subsequent 36 h of sustained endotoxin treatment, expression of ALS recovered to, and then rose above, that of their pair-fed controls. This effect was paralleled by other ternary complex components. The inductive effect of sustained endotoxemia relative to pair-fed controls could not be explained by differences in expression of GHR, SOCS-3, or CIS but coincided with normalized PEPCK and IGFBP-1 levels, suggesting better hepatic insulin sensitivity in these animals. These data may indicate that, in sustained endotoxemia, ALS levels are regulated through modulation of hepatic insulin sensitivity.
authors.affiliation: Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kong
authors.forename: Sue M
authors.initials: SM
authors.lastname: Firth
authors.forename: Robert C
authors.initials: RC
authors.lastname: Baxter
authors.forename: Patric J D
authors.initials: PJ
authors.lastname: Delhanty
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology*; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; D005947:Glucose; D006023:Glycoproteins; D017874:Immediate-Early Proteins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018975:Insulin-Like Growth Factor Binding Protein 5; D008070:Lipopolysaccharides; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D011506:Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D012097:Repressor Proteins; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; C491410:Socs3 protein, rat; C075944:insulin-like growth factor binding protein, acid labile subunit