Insulin treatment improves hepatic morphology and function through modulation of hepatic signals after severe trauma.
OBJECTIVE
The purpose of the present study was to determine the effect of insulin therapy on hepatic function, structure, and hepatic mRNA and protein cytokine expression during the hypermetabolic cascade post burn.


BACKGROUND
Liver function and morphology are crucial for survival of patients suffering from trauma, operations, or infections. Insulin decreased mortality and prevented the incidence of multiorgan failure in critically ill patients.


METHODS
Rats received a thermal injury and were randomly divided into the insulin or control group. Our outcome measures encompassed the effect of insulin on hepatic proteins, hepatic pro- and anti-inflammatory cytokines mRNA and proteins, hepatocyte proliferation, including Bcl-2 and hepatocyte apoptosis, with caspases-3 and caspases-9.


RESULTS
Insulin significantly improved hepatic protein synthesis by increasing albumin and decreasing c-reactive protein and fat (P < 0.05). Insulin decreased the hepatic inflammatory response signal cascade by decreasing hepatic pro-inflammatory cytokines mRNA and proteins IL-1beta and tumor necrosis factor at pretranslational levels. Insulin increased hepatic cytokine mRNA and protein expression of IL-2 and IL-10 at a pretranslational level when compared with controls (P < 0.05). Insulin increased hepatocyte proliferation along with Bcl-2 concentration, while decreasing hepatocyte apoptosis along with decreased caspases-3 and -9 concentration, thus improving liver morphology (P < 0.05).


CONCLUSIONS
Our data provide insight that insulin attenuates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade, thus restoring hepatic homeostasis, which has been shown to be critical for organ function and survival of critically ill patients.
Klein
Dagmar
D
Klinik und Poliklinik für Chirurgie, Klinikum der Universität Regensburg, Germany.
Schubert
Thomas
T
Horch
Raymund E
RE
Jauch
Karl-Walter
KW
Jeschke
Marc G
MG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001483:Base Sequence; D001707:Biopsy, Needle; D002056:Burns / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D015601:Injury Severity Score; D007328:Insulin / Q000494:pharmacology*; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity
D016207:Cytokines; D007328:Insulin; D012333:RNA, Messenger