Interleukin-13 (IL-13) is now shown to control hepatic glucose production, raising the possibility that targeting this cytokine may have therapeutic benefit against type 2 diabetes (J. Clin. Invest. 123, 261–271).

Using mice lacking IL-13, Kristopher Stanya et al. found that the mice developed hyperglycemia and hepatic insulin resistance. Mechanistically, the authors showed that gluconeogenesis enzymes were upregulated in the livers of the knockout mice. They found evidence that, acting through Stat3, IL-13 directly inhibited the transcription of gluconeogenic genes in hepatocytes. Moreover, IL-13 lost the ability to suppress glucose production in hepatocytes lacking Stat3 or an IL-13 receptor subunit.

As the immune system can directly regulate metabolic functions, it will be of interest to study the role of IL-13 in mice lacking this cytokine in specific cell populations to tease apart its direct effect on the liver from any additional effects on glycemic control via macrophages or other immune cells.