Insulin Signaling in a Bit of a Jam
| Autor: | Ajay Chawla, Vassily I. Kutyavin |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Inflammation biology Insulin medicine.medical_treatment Cell Normal tissue General Biochemistry Genetics and Molecular Biology Article Cell biology 03 medical and health sciences Insulin receptor 030104 developmental biology medicine.anatomical_structure Metabolic Diseases Hyperglycemia medicine biology.protein Humans Mevalonate pathway medicine.symptom Signal transduction Signal Transduction |
| Zdroj: | Cell. 165(2) |
| ISSN: | 1097-4172 |
| Popis: | Control of plasma glucose level is essential to organismal survival. Sustained inflammation has been implicated in control of glucose homeostasis in cases of infection, obesity, and type 2 diabetes; however, the precise role of inflammation in these complex disease states remains poorly understood. Here, we find that sustained inflammation results in elevated plasma glucose due to increased hepatic glucose production. We find that sustained inflammation suppresses CYP7A1, leading to accumulation of intermediate metabolites at the branch point of the mevalonate pathway. This results in prenylation of RHOC, which is concomitantly induced by inflammatory cytokines. Subsequent activation of RHO-associated protein kinase results in elevated plasma glucose. These findings uncover an unexpected mechanism by which sustained inflammation alters glucose homeostasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|