title: Hemorrhage induces the rapid development of hepatic insulin resistance.
abstract: Hyperglycemia is an early metabolic response to trauma and hemorrhage. The role of hepatic insulin resistance to the development of this hyperglycemia is not well understood. The aim of this study was to determine whether the liver becomes insulin resistant and to identify the particular hepatic insulin signaling pathways that may be compromised following trauma and hemorrhage. Male adult rats were bled to a mean arterial pressure of 40 mmHg and maintained at that pressure for 90 min followed by resuscitation with Ringer lactate. Data showed that trauma and hemorrhage rapidly induced profound hyperinsulinemia in combination with significant hyperglycemia, suggesting the development of insulin resistance. After trauma and hemorrhage, hepatic insulin signaling via the insulin-induced phosphatidylinositol 3 (PI3)-kinase-Akt pathway was abolished, whereas ERK1/2 signaling was relatively normal. The regulation (inhibition) of a hepatic-, insulin-, and the PI3-kinase-dependent gene, IGF binding protein-1, was also lost. The present study provides convincing evidence of a rapid onset hepatic insulin resistance following a combination of trauma and hemorrhage.
authors.affiliation: Department of Pathology, Division of Molecular and Cellular Pathology, The University of Alabama at Birmingham, 35294, USA.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Ma
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Kuebler
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Messina
mesh_terms: D000007:Abdominal Injuries / Q000503:physiopathology; D000818:Animals; D001786:Blood Glucose; D015870:Gene Expression / Q000502:physiology; D006470:Hemorrhage / Q000503:physiopathology*; D006943:Hyperglycemia / Q000503:physiopathology; D006946:Hyperinsulinism / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D008099:Liver / Q000503:physiopathology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases