Nutritional Regulation of Insulin-like Growth Factor-I Receptor mRNA Levels in Growing Chickens

1996 ◽  
Vol 60 (6) ◽  
pp. 979-982 ◽  
Author(s):  
Yuki Matsumura ◽  
Manabu Domeki ◽  
Kunio Sugahara ◽  
Tatsuo Kubo ◽  
Charles T. Roberts ◽  
...  
1991 ◽  
Vol 6 (1) ◽  
pp. 33-43 ◽  
Author(s):  
S. Goldstein ◽  
J. B. Harp ◽  
L. S. Phillips

ABSTRACT The liver is thought to be the locus of nutritional/hormonal regulation of circulating insulin-like growth factor-I (IGF-I). To probe the basis of nutritional regulation, we examined changes in serum IGF-I, hepatic content of extractable IGF-I immunoreactivity (a high Mr putative precursor) and hepatic IGF-I mRNA during fasting and refeeding in rats. Preliminary studies revealed that the hepatic level of IGF-I mRNA was consistently reduced only after food was withheld for 3 days, so the effects of refeeding were subsequently examined in such animals. After 3 days of fasting, animals lost 30% of their initial weight; weight regain was apparent within 3 h of refeeding ad libitum and, after 48 h, weight was comparable to initial fed levels. Fasting reduced levels of serum and extractable hepatic IGF-I to 19 and 26% of control (fed) values respectively (both P<0·005 vs control). There was no change in levels of serum IGF-I over the first 3 h of refeeding, but IGF-I rose above fasted levels at both 9 and 48 h (both P<0·005). Extractable hepatic IGF-I rose more slowly and was still below fasted levels after 9 h of refeeding, and modestly, but not significantly, greater than fasted levels after 48 h. The ratio of serum to hepatic IGF-I was decreased compared with control after 3 days of fasting, but increased after 3 and 9 h of refeeding (P<0·02 at 9 h). Northern blot analysis of total hepatic RNA revealed four species of IGF-I mRNA 0·8–1·1, 2·0, 4·0 and 7·5 kb in size. Each mRNA species fell to 15–28% of control levels after 3 days of fasting (all P<0·001). There was a prompt increase in each transcript after 3 h of refeeding, and all values were significantly (P<0·05) greater than fasted levels at 9 h but, at 48 h, most species were still below control levels. Levels of mRNA for the cytoskeletal proteins β-actin and cyclophilin also fell with fasting, but were restored more rapidly than IGF-I mRNA, to or above control levels after 3 h of refeeding. The observation that IGF-I expression was decreased at 3 h when β-actin and cyclophilin were normalized suggests specificity of regulation. Despite the temporal incongruity between IGF-I mRNA and serum and hepatic IGF-I, there were highly significant correlations (all P<0·002) between each pair of parameters. Since refeeding of fasted animals led to a rise in IGF-I mRNA which preceded rises in serum and hepatic IGF-I, our findings are consistent with the hypothesis that nutritional regulation of circulating IGF-I involves modulation at the level of hepatic IGF-I mRNA. The changes in the ratio of hepatic to serum IGF-I during fasting and refeeding indicate that there may also be regulation at the level of hepatic release.


1996 ◽  
Vol 319 (2) ◽  
pp. 455-461 ◽  
Author(s):  
Simon S WING ◽  
Nathalie BEDARD

Upon fasting, the ubiquitin-dependent proteolytic system is activated in skeletal muscle in parallel with the increases in rates of proteolysis. Levels of mRNA encoding the 14 kDa ubiquitin-conjugating enzyme (E214k), which can catalyse the first irreversible reaction in this pathway, rise and fall in parallel with the rates of proteolysis [Wing and Banville (1994) Am. J. Physiol. 267, E39-E48], indicating that the conjugation of ubiquitin to proteins is a regulated step. To characterize the mechanisms of this regulation, we have examined the effects of insulin, insulin-like growth factor I (IGF-I) and des(1–3) insulin-like growth factor I (DES-IGF-I), which does not bind IGF-binding proteins, on E214k mRNA levels in L6 myotubes. Insulin suppressed levels of E214k mRNA with an IC50 of 4×10-9 M, but had no effects on mRNAs encoding polyubiquitin and proteasome subunits C2 and C8, which, like E214k, also increase in skeletal muscle upon fasting. Reduction of E214k mRNA levels was more sensitive to IGF-I with an IC50 of approx. 5×10-10 M. During the incubation of these cells for 12 h there was significant secretion of IGF-I-binding proteins into the medium. DES-IGF-I, which has markedly reduced affinity for these binding proteins, was found to potently reduce E214k mRNA levels with an IC50 of 3×10-11 M. DES-IGF-I did not alter rates of transcription of the E214k gene, but enhanced the rate of degradation of the 1.2 kb mRNA transcript. The half-life of the 1.2 kb transcript was approximately one-third that of the 1.8 kb transcript and can explain the more marked regulation of this transcript observed previously. This indicates that the additional 3´ non-coding sequence in the 1.8 kb transcript confers stability. These observations suggest that IGF-I is an important regulator of E214k expression and demonstrate, for the first time, stimulation of degradation of a specific mRNA transcript by this hormone, while overall RNA accumulates.


Metabolism ◽  
1995 ◽  
Vol 44 ◽  
pp. 50-57 ◽  
Author(s):  
Jean-Marie Ketelslegers ◽  
Dominique Maiter ◽  
Marc Maes ◽  
Louis E. Underwood ◽  
Jean-Paul Thissen

2013 ◽  
Vol 111 (2) ◽  
pp. 201-206 ◽  
Author(s):  
Chao Wen ◽  
Ping Wu ◽  
Yueping Chen ◽  
Tian Wang ◽  
Yanmin Zhou

The present study aimed to investigate the responses of broilers with different hatching weights (HW) to dietary methionine (Met). A total of 192 1-d-old Arbor Acres broiler chicks with different HW (heavy: 48·3 (sem 0·1) g and light: 41·7 (sem 0·1) g) were allocated to a 2 (HW) × 2 (Met) factorial arrangement with six replicates of eight chicks. Control starter (1–21 d) and finisher (22–42 d) diets contained 0·50 and 0·43 % Met, respectively. Corresponding values for a high-Met treatment were 0·60 and 0·53 %. Light chicks had poorer (P< 0·05) growth performance and breast muscle weight and lower (P< 0·05) insulin-like growth factor-I (IGF-I) concentration and mRNA level in breast muscle than heavy chicks when both were fed the control diets. High-Met diets improved performance and promoted breast muscle growth and IGF-I concentration in light chicks (P< 0·05). Increased IGF-I and target of rapamycin (TOR) mRNA levels as well as decreased eIF4E-binding protein 1 (4EBP1), atrogin-1 and forkhead box O 4 (FOXO4) mRNA levels were induced by high-Met diets in light chicks (P< 0·05). In conclusion, the Met requirement of broilers might depend on their HW and Met levels used in the control diets in the present study were adequate for heavy chicks but inadequate for light chicks, resulting in poorer performance and breast muscle growth, which were improved by increasing dietary Met supply presumably through alterations in IGF-I synthesis and gene expression of the TOR/4EBP1 and FOXO4/atrogin-1 pathway.


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