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Comment
. 2012 Mar;153(3):1010-3.
doi: 10.1210/en.2011-2183.

One step from prediabetes to diabetes: hypothalamic inflammation?

Dongsheng Cai  1
Affiliations
Comment

One step from prediabetes to diabetes: hypothalamic inflammation?

Dongsheng Cai. Endocrinology. 2012 Mar.
No abstract available

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Figures

Fig. 1.
Fig. 1.
Hypothalamic inflammation links central insulin resistance to diabetes. Hypothalamic regulation of feeding, body weight, and glucose homeostasis is mediated by multiple signaling pathways including insulin singling. The hypothalamic insulin signaling cascade is directed by activation of insulin receptor, IRS proteins, and downstream phosphatidylinositol-3-OH kinase (PI3K), which control AKT and FOXO to regulate gene expression of neuropeptides such as proopiomelanocortin (POMC) and neuropeptide Y (NPY). In IRS2-deficient mice, some of them can develop diabetes, but others present only prediabetic syndrome, likely due to the differential compensatory effects by IRS1. The compromised compensation of hypothalamic IRS1 signaling in diabetic IRS2-deficient mice is related to the certain pattern and perhaps increased magnitude of hypothalamic inflammation. Such hypothalamic changes in IRS2-deficient mice align with recent literature showing the central mechanisms of obesity and T2D involve IκB kinase β (IKKβ)/NF-κB- and JNK-mediated hypothalamic inflammation, a central pathogenic event caused by overnutrition-induced endoplasmic reticulum (ER) stress, oxidative stress, autophagy defects, and cytokine activation. AA, Amino acids; AP1, activator protein-1; FFA, free fatty acid; FOXO, forkhead box O; PIP2, phosphatidylinositol 4,5-bisphosphate; PTEN, phosphate and tensin homolog.
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