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Regulation of hepatic insulin receptor activity following injury
- Source :
- American Journal of Physiology-Gastrointestinal and Liver Physiology. 306:G886-G892
- Publication Year :
- 2014
- Publisher :
- American Physiological Society, 2014.
-
Abstract
- Impaired insulin receptor (IR) activity has been found in various models of insulin resistance, including models of injury or critical illness and Type 2 diabetes. However, mechanisms that modulate IR function remain unclear. With an animal model of critical-illness diabetes, we found insulin-induced IR tyrosine phosphorylation in the liver was impaired as early as 15 min following trauma and hemorrhage. Possible mechanisms for this defect were examined, including IR protein levels and IR posttranslational modifications. The total amounts of hepatic IRα and IRβ subunits and the membrane localization of the IR were not altered by trauma and hemorrhage, and, likewise, no change in IR tyrosine nitration was found in the liver. However, there was a decrease in the level of protein O-linked β-N-acetlyglucosamine (O-GlcNac) modification on Ser/Thr in the liver following trauma and hemorrhage. Inhibition of JNK increased IR O-GlcNac modification, implicating an involvement of JNK. These findings suggest that a balance between O-GlcNac modification and JNK-induced phosphorylation may exist, with decreased Ser/Thr O-GlcNac modification following trauma and hemorrhage, allowing JNK to phosphorylate the IR on neighboring Ser/Thr residues, which subsequently inhibits IR activity. The present studies suggest potential mechanisms of hemorrhage-induced defects in IR activity and a potential role for acutely decreased O-GlcNac and increased serine phosphorylation of the IR.
- Subjects :
- Male
medicine.medical_specialty
Insulin Receptor Substrate Proteins
Physiology
Hormones and Signaling
Type 2 diabetes
Biology
N-Acetylglucosaminyltransferases
Serine
chemistry.chemical_compound
Insulin resistance
Physiology (medical)
Diabetes mellitus
Internal medicine
medicine
Animals
Hepatology
JNK Mitogen-Activated Protein Kinases
Gastroenterology
Tyrosine phosphorylation
medicine.disease
Receptor, Insulin
Rats
Insulin receptor
Endocrinology
Liver
chemistry
biology.protein
Phosphorylation
Insulin Resistance
Gastrointestinal Hemorrhage
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 15221547 and 01931857
- Volume :
- 306
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Accession number :
- edsair.doi.dedup.....789d0dd75f03506eacee4bcc771e89d8