XBP-1s Is Linked to Suppressed Gluconeogenesis in the Ebb Phase of Burn Injury
| Autor: | Alexandra H. Marshall, Marc G. Jeschke, Natasha C. Brooks, Nour Qa'aty, Darren Boehning, Yaeko Hiyama |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Blood Glucose
Male X-Box Binding Protein 1 Burn injury medicine.medical_specialty Nerve Tissue Proteins Regulatory Factor X Transcription Factors Biology Rats Sprague-Dawley Downregulation and upregulation Internal medicine Genetics medicine Glucose homeostasis Animals Insulin Molecular Biology Genetics (clinical) Thermal injury ATF6 Endoplasmic reticulum Gluconeogenesis Forkhead Transcription Factors Articles Endoplasmic Reticulum Stress Rats DNA-Binding Proteins Endocrinology Liver biology.protein Unfolded protein response Glucose-6-Phosphatase Molecular Medicine Burns Glucose 6-phosphatase Transcription Factors |
| Popis: | The first 24 h following burn injury is known as the ebb phase and is characterized by a depressed metabolic rate. While the postburn ebb phase has been well described, the molecular mechanisms underlying this response are poorly understood. The endoplasmic reticulum (ER) regulates metabolic rate by maintaining glucose homeostasis through the hepatic ER stress response. We have shown that burn injury leads to ER stress in the liver during the first 24 h following thermal injury. However, whether ER stress is linked to the metabolic responses during the ebb phase of burn injury is poorly understood. Here, we show in an animal model that burn induces activation of activating transcription factor 6 (ATF6) and inositol requiring enzyme-1 (IRE-1) and this leads to increased expression of spliced X-box binding protein-1 (XBP-1s) messenger ribonucleic acid (mRNA) during the ebb phase. This is associated with increased expression of XBP-1 target genes and downregulation of the key gluconeogenic enzyme glucose-6-phosphatase (G6Pase). We conclude that upregulation of the ER stress response after burn injury is linked to attenuated gluconeogenesis and sustained glucose tolerance in the postburn ebb phase. |
| Databáze: | OpenAIRE |
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