Glucose infusion suppresses surgery-induced muscle protein breakdown by inhibiting ubiquitin-proteasome pathway in rats.
BACKGROUND
It appears to have been well established that after surgery, protein catabolism is accelerated and glucose infusion suppresses the catabolic reactions. However, in the early postoperative period, the effects of surgical stress and glucose infusion on muscle protein catabolism and the related mechanisms remain unclear.


METHODS
Rats undergoing laparotomy were infused with acetated Ringer's solution (10 ml x kg(-1) x h(-1)) without glucose (control) or containing 1% or 5% glucose. The infusion was continued for a further 4 h after the surgical treatment. The catabolic index, excretion of urinary nitrogen and 3-methylhistidine, and release of tyrosine and 3-methylhistidine from isolated muscle were determined. Furthermore, muscular mRNA expression of proteolytic-related genes (atrogin-1/MAFbx, muscle ring finger-1, mu- and m-calpain, and cathepsin L and H) and phosphorylation of components of insulin signaling (forkhead box O3 and protein kinase B) were evaluated.


RESULTS
Surgery increased the catabolic index, and this increase was suppressed by glucose infusion (both 1% and 5%). In the control group, mRNA expression of atrogin-1/MAFbx and muscle ring finger-1 was increased, and they were suppressed in the two glucose groups. Furthermore, insulin signaling (phosphorylation of protein kinase B and forkhead box O3) in muscles was stimulated by glucose infusion.


CONCLUSIONS
The present study indicates that glucose infusion, even at a relatively low rate, suppresses muscle protein breakdown in the early postoperative period. The mechanism of this effect is related to the suppression of the ubiquitin-proteasome pathway, accompanied by activation of insulin signaling.
Mikura
Mayumi
M
New Product and Business Development, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan. mikuramu@otsukakj.co.jp
Yamaoka
Ippei
I
Doi
Masako
M
Kawano
Yuichi
Y
Nakayama
Mitsuo
M
Nakao
Reiko
R
Hirasaka
Katsuya
K
Okumura
Yuushi
Y
Nikawa
Takeshi
T
D000818:Animals; D005947:Glucose / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D008660:Metabolism / Q000187:drug effects / Q000502:physiology; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011183:Postoperative Complications / Q000378:metabolism / Q000517:prevention & control*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D025801:Ubiquitin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D009124:Muscle Proteins; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D005947:Glucose