Fig. 7: Working model of the effect of insulin signaling on podocyte homeostasis by the targeting of podocyte Orai1. | Nature Communications

Fig. 7: Working model of the effect of insulin signaling on podocyte homeostasis by the targeting of podocyte Orai1.

From: Insulin-activated store-operated Ca2+ entry via Orai1 induces podocyte actin remodeling and causes proteinuria

Fig. 7: Working model of the effect of insulin signaling on podocyte homeostasis by the targeting of podocyte Orai1.

Insulin stimulates Orai1 leading to an aberrant [Ca2+]i signaling, which in turn activates calcineurin and causes synaptopodin degradation, actin cytoskeleton remodeling, increased contractility, and motility, and dysfunction of slit-diaphragm integrity. Acute (or short-term) stimulation of Orai1 by insulin receptor or receptor tyrosine kinases causes reversible physiological changes in the podocyte actin cytoskeleton. This may contribute to slit-diaphragm plasticity and/or survival against stress or injury. In contrast, chronic stimulation or hyperactivation of Orai1 activation leads to irreversible pathological changes such as podocyte foot process effacement and severe proteinuria.

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