Insulin prevents liver damage and preserves liver function in lipopolysaccharide-induced endotoxemic rats.
OBJECTIVE
Liver integrity and function are crucial for survival of patients suffering from trauma, operations or infections. Insulin decreased mortality and prevented the incidence of multi organ failure and infection in critically ill patients. The aim of the present study was to determine whether insulin exerts positive effects on hepatic homeostasis and function during endotoxemia.


METHODS
Endotoxemic rats received either saline or insulin. Hepatic morphology and function was determined by measuring the effect of insulin on liver proteins, enzymes, hepatocyte apoptosis and proliferation including caspases-3 and -9 and Bcl-2. Intrahepatic ATP, glucose and lactate concentration were determined by bioluminescence. To determine possible molecular changes the effect of insulin on hepatic cytokine mRNA and gene profile analysis were assessed.


RESULTS
Insulin significantly improved hepatic protein synthesis by increasing albumin and decreasing c-reactive protein, P<0.05. Insulin attenuated hepatic damage by decreasing AST and ALT, P<0.05. Improved liver morphology was due to decreased hepatocyte apoptosis along with decreased caspase-3 concentration and increased hepatocyte proliferation along with Bcl-2 concentration, P<0.05. Insulin decreased hepatic IL-1beta, IL-6 and MIF mRNA and improved hepatic glucose metabolism and glycolysis, P<0.05. GeneChip analysis revealed an anti-inflammatory effect of insulin.


CONCLUSIONS
Insulin improves hepatic integrity, hepatic glucose metabolism and hepatic function by increasing cell survival and attenuating the hepatic inflammatory response in endotoxemic rats.
Jeschke
Marc G
MG
Shriners Hospital for Children and Department of Surgery, The University Texas Medical Branch, Galveston Burns Unit, 815 Market Street, Galveston, TX 77550, USA. Mcjeschke@hotmail.com
Rensing
Hauke
H
Klein
Dagmar
D
Schubert
Thomas
T
Mautes
Anke E M
AE
Bolder
Ulrich
U
Croner
Roland S
RS
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002455:Cell Division; D019938:Cyclin D1 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004573:Electrolytes / Q000097:blood; D019446:Endotoxemia / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000188:drug therapy / Q000276:immunology
D000209:Acute-Phase Proteins; D001786:Blood Glucose; D016207:Cytokines; D004573:Electrolytes; D007004:Hypoglycemic Agents; D007328:Insulin; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019938:Cyclin D1; D019344:Lactic Acid; D000255:Adenosine Triphosphate; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases