Persistent insulin signaling coupled with restricted PI3K activation causes insulin-induced vasoconstriction.

Persistent insulin signaling coupled with restricted PI3K activation causes insulin-induced vasoconstriction. Am J Physiol Heart Circ Physiol. 2019 Oct 11;: Authors: Olver TD, Grunewald ZI, Ghiarone T, Restaino RM, Sales ARK, Park LK, Thorne PK, Ganga RR, Emter CA, Lemon PW, Shoemaker JK, Manrique-Acevedo C, Martinez-Lemus LA, Padilla J Abstract Insulin modulates vasomotor tone through vasodilator and vasoconstrictor signaling pathways. The purpose of the present work was to determine whether insulin-stimulated vasoconstriction is a pathophysiological phenomenon that can result from a combination of persistent insulin signaling, suppressed PI3K activation and an ensuing relative increase in MAPK/endothelin-1 (ET-1) activity. First, we examined previously published work from our group where we assessed changes in lower limb blood flow in response to an oral glucose tolerance test (endogenous insulin stimulation) in lean and obese subjects. The new analyses showed that the peak rise in vascular resistance during the postprandial state was greater in obese compared to lean subjects. Next, we extended on these findings by demonstrating that insulin-induced vasoconstriction in isolated resistance arteries from obese subjects was attenuated with ET-1receptor antagonism, thus implicating ET-1 signaling in this constriction response. Last, we examined in isolated resistance arteries from pigs the dual roles of persistent insulin signaling an...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research