Investigating the causes for decreased levels of glutathione in individuals with type II diabetes.

Published: March, 2015 in the Journal PLOS One

Individuals with T2DM have lower levels of glutathione (GSH) than non-diabetic individuals due to compromise of GSH synthesis and of the enzymes needed to form GSH.  The decrease in GSH was due to a decrease in the  the GSH forming enzymes glutamine cysteine ligase catalytic unit (GCLC) and glutathione synthase (GS).  The decrease in glutathione is accompanied by a pro-inflammatory pattern in these individuals and includes elevations of interleukin-6 (IL-6), IL-10 and transforming growth factor (TGF)–β, which are considered pro-inflammatory.Associated with low GSH, the cytokines supporting efficient defense against bacterial infection were low and the ability of the immune cells used to fight infection was shown to be low.

Overall, the changes in the cytokine picture of individuals with T2DM were consistent with a decreased resistance against bacterial growth of intracellular infection with Mycobacterium tuberculosis. The study also showed repletion of glutathione using liposomal glutathione in in vitrocell culture was able to improve the immune cell defense against the growth of M. tb.

In this study, we report that individuals with T2DM have lower levels of glutathione (GSH) due to compromised levels of GSH synthesis and metabolism enzymes. Transforming growth factor beta (TGF-β), a cytokine that is known to decrease the expression of the catalytic subunit of glutamine-cysteine ligase (GCLC) was found in increased levels in the plasma samples from individuals with T2DM, explaining the possible underlying mechanism that is responsible for decreased levels of GSH in individuals with T2DM.

PMID: 25790445