ABSTRACT
The GH-dependent, hepatocyte-derived acid-labile subunit (ALS) regulates IGF release from the serum by forming ternary complexes containing IGF binding protein (IGFBP)-3 or IGFBP-5. Malnutrition suppresses ALS and IGF-I expression in a development-dependent manner. Our aim was to investigate whether the effect of feeding following fasting was similarly age dependent. We fasted juvenile and adult rats for 48 h and then refed them, collecting serum and liver tissue at 8, 24, and 48 h. These were compared with rats before fasting (0 h controls) and animals fed throughout the study (free-fed controls). During fasting, serum ALS fell to 25 +/- 5.3% of 0 h controls in juveniles but only 56 +/- 6% in adults. Within 24 h of refeeding, ALS in juveniles had returned to 0 h control levels, and by 48 h to free-fed levels, whereas there was no significant refeeding response in adults during this period. Circulating IGF-I and IGFBP-5 showed similar age-dependent responses to refeeding, rising significantly faster in juveniles. IGFBP-3 did not show this response. Furthermore, hepatic ALS and IGF-I mRNA showed no age-differential response to fasting and refeeding, suggesting posttranscriptional regulation. Neither regulation of hepatic GH receptor nor ALS clearance rates could explain the age-dependent effect. We hypothesize that development-dependent regulation of ALS and IGF-I during refeeding may involve a posttranscriptional hepatic response that is not GH dependent.
Subject(s)
Aging , Carrier Proteins/blood , Carrier Proteins/genetics , Fasting , Food , Gene Expression Regulation, Developmental , Glycoproteins/blood , Glycoproteins/genetics , Animals , Binding, Competitive , Body Weight , Carrier Proteins/chemistry , Glycoproteins/chemistry , Insulin/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor Binding Protein 5/blood , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor I/genetics , Kinetics , Liver/chemistry , Male , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Receptors, Somatotropin/geneticsABSTRACT
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.
Subject(s)
Carrier Proteins/genetics , Carrier Proteins/metabolism , Endotoxemia/metabolism , Endotoxemia/physiopathology , Glycoproteins/genetics , Glycoproteins/metabolism , Repressor Proteins , Transcription Factors , Animals , Body Weight/drug effects , Eating/drug effects , Gene Expression/physiology , Glucose/metabolism , Immediate-Early Proteins/genetics , Immediate-Early Proteins/metabolism , Insulin/metabolism , Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Protein 1/genetics , Insulin-Like Growth Factor Binding Protein 5/blood , Lipopolysaccharides/pharmacology , Liver/metabolism , Male , Phosphoenolpyruvate Carboxykinase (GTP)/genetics , Phosphoenolpyruvate Carboxykinase (GTP)/metabolism , Protein Structure, Tertiary , Proteins/genetics , Proteins/metabolism , RNA, Messenger/analysis , Radioimmunoassay , Rats , Rats, Sprague-Dawley , Receptors, Somatotropin/genetics , Receptors, Somatotropin/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling ProteinsABSTRACT
BACKGROUND: It has been reported that glycine may protect donor small intestine against hypothermic ischemia before transplantation. This is consistent with the documented role of glycine as a natural cytoprotectant. OBJECTIVE: Using an in vivo rodent model, we sought to determine whether exposure to a 20% glycine solution reduces the extent of warm ischemia-reperfusion injury. METHODS: Wistar rats (n = 50) underwent laparotomy. A baseline group did not receive any further intervention. The remaining animals had cannulation of the aorta before the initiation of intestinal ischemia (30 minutes) followed by reperfusion (30 minutes). Using a factorial design, rats were randomized to receive local tissue perfusion with either normal saline or a 20% glycine solution during either the preischemia or the prereperfusion phase. Standardized segments of small intestine were removed at the end of the study period to determine the extent of ischemia-reperfusion injury. RESULTS: Perfusion with 20% glycine increased mucosal protein content (p < .05), increased mucosal DNA content (p < .05), reduced intestinal myeloperoxidase activity (p < .05), and maintained mucosal glutaminase activity. This was true regardless of whether glycine was administered during the preischemia phase or the prereperfusion phase. CONCLUSIONS: Local perfusion with 20% glycine can diminish warm ischemia-reperfusion injury to the rat small intestine in an in vivo model. The role of glycine supplementation should be evaluated in situations where hemodynamic instability may be responsible for breakdown in the gut barrier.