Dysfunction of brain pericytes contributes to development of type2 diabetes mellitus

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In this study, we hypothesized that brain pericytes are a glucose sensing cell and respond to high glucose levels to impair the blood-brain barrier (BBB) and hypothalamic neuron. Our major findings are as follows; (1) BBB function was impaired in high-fat diet-induced obese mouse with hyperglycemia, (2) High glucose levels enhanced TNF-a-induced release of MMP-9 from cultured brain pericytes, (3) Brain pericytes regulate insulin sensitivity and anorexic signaling in the hypothalamic neuron by releasing soluble factors. These results suggest that changes in brain pericyte-derived soluble factors under hyperglycemia contribute to the impairment of BBB and the insulin resistance in hypothalamic neurons.