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- W2948866412 abstract "Defective glucose uptake in adipocytes leads toimpaired metabolic homeostasis and insulin resistance, hallmarks oftype 2 diabetes. Extracellular ATP-derived nucleotides andnucleosides are important regulators of adipocyte function, but thepathway for controlled ATP release from adipocytes is unknown.Here, we investigated whether Pannexin 1 (Panx1) channels controlATP release from adipocytes and contribute to metabolichomeostasis. Our studies show that adipocytes express functionalPannexin 1 (Panx1) channels that can be activated to release ATP byknown mechanisms including alpha adrenergic stimulation andcaspase-mediated C-terminal cleavage during apoptosis. Further, weidentify insulin as a novel activator of Panx1 channels.Pharmacologic inhibition or selective genetic deletion of Panx1from adipocytes decreased insulin-induced glucose uptake in vitroand in vivo and exacerbated diet-induced insulin resistance inmice. In obese humans, Panx1 expression in adipose tissue isincreased and correlates with the degree of insulin resistance.Although in other systems extracellular ATP has been shown to bechemotactic for immune cells such as macrophages, we observed nodifference in the level of macrophage infiltration or inflammationin adipose tissue of diet-induced obese, insulin resistantAdipPanx1 KO mice, (mice in which Panx1 was selectively deleted inadipocytes). We also observed that deficiency of the ATP receptorP2Y2 on myeloid cells in mice did not affect glucose intolerance ina model of diet-induced obesity and insulin resistance. However,mice which lack P2Y2 receptors in myeloid cells show decreasedcrown-like structure formation in perigonadal adipose tissuealthough the amount of macrophages within the tissue are notdifferent from WT mice. In conclusion, Panx1 channel activitycontrols metabolic homeostasis in adipocytes, namely through theregulation of insulin-stimulated glucose uptake." @default.
- W2948866412 created "2019-06-14" @default.
- W2948866412 creator A5015372458 @default.
- W2948866412 date "2017-08-09" @default.
- W2948866412 modified "2023-09-26" @default.
- W2948866412 title "Pannexin 1 and Adipose Tissue" @default.
- W2948866412 doi "https://doi.org/10.18130/v3mp2j" @default.
- W2948866412 hasPublicationYear "2017" @default.
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