Insulin-like growth factor 1 has beneficial effects, whereas growth hormone has limited effects on postoperative protein metabolism, gut integrity, and splenic weight in rats with chronic mild liver injury.
BACKGROUND
Both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) improve protein metabolism after surgical insult in subjects without liver disease. However, these effects in chronic liver injury, in which the GH-IGF-1 axis is impaired, have not been investigated. We examined the anabolic effects of GH and IGF-1 after gastrectomy in rats with chronic mild liver injury.


METHODS
Rats with chronic mild liver injury induced by thioacetamide were used. After gastrectomy, the rats were randomized into vehicle control, GH, and IGF-1 groups. In the latter two groups, 0.8 IU/kg/d of GH or 4 mg/kg/d of IGF-1 was infused for 72 hours. Anabolic effects were assessed by body weight change, 3-methylhistidine (3-MH) excretion, nitrogen excretion, and whole-body protein turnover. Organ weights, plasma levels of glucose, insulin, and IGF-1, tissue IGF-1 levels, hepatic messenger RNA (mRNA) content, and intestinal structure were also determined.


RESULTS
Both GH and IGF-1 decreased nitrogen excretion. IGF-1, but not GH, increased postoperative body weight, whole-body protein turnover, and splenic weight. IGF-1 reduced atrophy of the intestinal mucosa. GH treatment increased hepatic IGF-1-mRNA and the plasma IGF-1 level, whereas IGF-1 treatment increased the plasma IGF-1 level with no change in the hepatic IGF-1-mRNA content. There were no significant differences in plasma glucose or insulin levels among the three groups. Neither GH nor IGF-1 affected the gastrocnemius muscle IGF-1 level.


CONCLUSIONS
IGF-1 has beneficial effects, whereas GH has only limited effects on post-operative protein metabolism, gut integrity, and splenic weight in chronic mild liver injury.
Inaba
T
T
Department of Surgery I, Faculty of Medicine, University of Tokyo, Japan.
Saito
H
H
Fukushima
R
R
Hashiguchi
Y
Y
Lin
M T
MT
Inoue
T
T
Fukatsu
K
K
Muto
T
T
Oka
T
T
Takenaka
A
A
Takahashi
S
S
Noguchi
T
T
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015152:Blotting, Northern; D001835:Body Weight / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury; D002908:Chronic Disease; D004064:Digestive System / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D007422:Intestines / Q000473:pathology / Q000648:ultrastructure; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008871:Microvilli / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000737:chemistry; D009584:Nitrogen / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011184:Postoperative Period; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D013853:Thioacetamide
D001786:Blood Glucose; D007328:Insulin; D011506:Proteins; D012333:RNA, Messenger; D013853:Thioacetamide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D009584:Nitrogen