IL-13 and hepatic gluconeogenesis

When I started learning about immunology I held a conviction that the immunity serves only to combat infections and pathogens. Perhaps the major change I have acquired in my understanding of immune processes is that the function of the immune system could be more permeating and extend to broader activities than just the defense. What we call the immune system works in situations well beyond the strict response to pathogenic organisms. It does not necessarily fight foreign entities as it may accommodate them (in case of microbiota) and also it has the intriguing links with the metabolism. I have found a publication that adds an interesting voice in support of such more general role of the immune system. It turns out that the cytokine IL-13 which is an important player in Th2 branch of immunity may influence how our body maintains one of the most important metabolic indicators.

The link: http://www.jci.org/articles/view/64941

Authors show data that mice deleted for gene encoding IL-13 display the impaired control of glucose level in the blood. Such defect appears to be a systemic one since it comprises both the increased production of glucose by liver cells as well as the reduced glucose uptake by muscles. Additionally, investigators delve into the molecular mechanism that underlies the IL-13-dependent control over the glucose production in the liver. It turns out that the transcription factor STAT3 could be the mediator between IL-13 signaling and genes involved in hepatic gluconeogenesis. Other than that authors attempt to identify the cellular population which may be responsible for the release of IL-13 in the liver and suggest that these could be NKT cells.

I am not really sure if it is sound to speculate in such way but there is at least the theoretical possibility that the exposure to parasites that provoke Th2-skewed response (like helminths) could protect from developing type II diabetes. The only problem is that relatively benign organisms inhabit the gastrointestinal tract and their influence may not extend to the liver whereas those that infect systemically (like Schistosoma mansoni) are too dangerous to be treated as a therapeutic agent. However, schistosome eggs are already applied as support in the treatment of excessive gut inflammation. May they be helpful in the regulation of glucose level?

Stanya KJ, Jacobi D, Liu S, Bhargava P, Dai L, Gangl MR, Inouye K, Barlow JL, Ji Y, Mizgerd JP, Qi L, Shi H, McKenzie AN, & Lee CH (2013). Direct control of hepatic glucose production by interleukin-13 in mice. The Journal of clinical investigation, 123 (1), 261-71 PMID: 23257358

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