handdator

Visa fullständig version : Dietärt nitrit ökar insulinkänslighet via GLUT4-translokering.


tjing
2013-10-28, 13:57
Dietary Nitrite Improves Insulin Signaling Through GLUT4 Translocation.

Abstract:

Diabetes mellitus type 2 is a syndrome of disordered metabolism with inappropriate hyperglycemia due to a reduction in the biological effectiveness of insulin. Type 2 diabetes is associated with an impaired nitric oxide (NO) pathway that likely serves as the key link between metabolic disorders and cardiovascular disease.

Insulin-mediated translocation of GLUT4 involves the PI3/Akt kinase signal cascade that results in activation of eNOS. eNOS is dysfunctional during diabetes. We hypothesize that loss of eNOS-derived NO terminates the signaling cascade and therefore cannot activate GLUT4 translocation and that dietary nitrite may repair this pathway.

In this study, we administered 50mg/L sodium nitrite to db/db diabetic mice for 4 weeks. Following 4 weeks treatment, the db/db mice experienced less weight gain, improved fasting glucose levels and reduced insulin levels.

Cell culture experiments using CHO-HIRc-mycGLUT4eGFP cell lines stably expressing insulin receptor and mycGLUT4GFP protein as well as L6 skeletal muscle cells stably expressing rat GLUT4 with a myc epitope (L6-GLUT4myc), we find that NO, nitrite and GSNO stimulates GLUT 4 translocation independent of insulin that is inhibited by NEM. Collectively our data suggests that nitrite improves insulin signaling through restoration of NO dependent nitrosation of GLUT4 signaling translocation.

These data suggests that NO mediated nitrosation of GLUT4 by nitrite or other nitrosating agents is necessary and sufficient for GLUT4 translocation in target tissue. Description of this pathway may justify a high nitrate/nitrite diet along with the glycemic index to provide a safe and nutritional regimen for the management and treatment of diabetes.

http://www.ncbi.nlm.nih.gov/pubmed/24157451

Free Radic Biol Med. 2013 Oct 21