Thread by @nick_krontiris

This one found that prolonged physiological and supraphysiological hyperinsulinemia can induce blunted acute insulin signaling, reduced insulin-stimulated glucose uptake, transcriptomic changes, and affect genes in insulin signaling pathways.

- "We demonstrated that prolonged physiological and supraphysiological hyperinsulinemia induced a reduction of AKT and ERK signaling and insulin-stimulated glucose uptake..."

- "Remarkably, while serum starvation partially reversed the effects of overnight hyperinsulinemia, much of the impaired acute insulin signaling and transcriptomic remodeling was sustained after 6 h of insulin withdrawal and serum starvation...

"...suggesting that stable molecular changes underlie these differences. The effects of prolonged hyperinsulinemia were insulin dose-dependent from the physiological to the supraphysiological range."

- "the impaired insulin response in our system can be partially accounted for by INSR downregulation at the transcription level and also used transcriptomic profiling to discover new factors that regulate insulin signaling in our system including SIN3A, JUND, MAX and MXI1."

Human and mouse muscle transcriptomic analyses identify insulin receptor mRNA downregulation in hyperinsulinemia-associated insulin resistance (open access, in vitro)

doi.org/10.1096/fj.202…

#InsulinResistance #MetabolicSyndrome