Other
14 Authors
- Stanya KJ,
- Bhargava P,
- Ji Y,
- Qi L,
- Mizgerd JP,
- Liu S,
- Barlow JL,
- Dai L,
- McKenzie AN,
- Inouye K,
- Gangl MR,
- Lee CH,
- Shi H,
- Jacobi D
| First Author | Stanya KJ | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 1 | Pages | 261-71 |
| PubMed ID | 23257358 | Mgi Jnum | J:194510 |
| Mgi Id | MGI:5473954 | Doi | 10.1172/JCI64941 |
| Citation | Stanya KJ, et al. (2013) Direct control of hepatic glucose production by interleukin-13 in mice. J Clin Invest 123(1):261-71 |
| abstractText | Hyperglycemia is a result of impaired insulin action on glucose production and disposal, and a major target of antidiabetic therapies. The study of insulin-independent regulatory mechanisms of glucose metabolism may identify new strategies to lower blood sugar levels. Here we demonstrate an unexpected metabolic function for IL-13 in the control of hepatic glucose production. IL-13 is a Th2 cytokine known to mediate macrophage alternative activation. Genetic ablation of Il-13 in mice (Il-13-/-) resulted in hyperglycemia, which progressed to hepatic insulin resistance and systemic metabolic dysfunction. In Il-13-/- mice, upregulation of enzymes involved in hepatic gluconeogenesis was a primary event leading to dysregulated glucose metabolism. IL-13 inhibited transcription of gluconeogenic genes by acting directly on hepatocytes through Stat3, a noncanonical downstream effector. Consequently, the ability of IL-13 to suppress glucose production was abolished in liver cells lacking Stat3 or IL-13 receptor alpha1 (Il-13ralpha1), which suggests that the IL-13Ralpha1/Stat3 axis directs IL-13 signaling toward metabolic responses. These findings extend the implication of a Th1/Th2 paradigm in metabolic homeostasis beyond inflammation to direct control of glucose metabolism and suggest that the IL-13/Stat3 pathway may serve as a therapeutic target for glycemic control in insulin resistance and type 2 diabetes. |
