What question did this study set out to answer?

To explore the role of the N-degron pathway in glucose and insulin homeostasis through SQSTM1-mediated lysosomal degradation of RXRA.

May 17, 2026Autophagy1 citations

The N-degron pathway regulates glucose and insulin homeostasis through the lysosomal degradation of RXRA/RXRα via SQSTM1/p62

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EJEui Jung JungSeoul National University HKHye Yeon KimSeoul National University TBTae Hyun BaeSeoul National University

Key Points

To explore the role of the N-degron pathway in glucose and insulin homeostasis through SQSTM1-mediated lysosomal degradation of RXRA.
Utilized ATB1002 to activate SQSTM1 as an N-recognin in mice models of prediabetes and T2D.
Examined the effects of SQSTM1 agonists on RXRA degradation and insulin secretion.
Assessed glucose-stimulated insulin responses in treated models.
SQSTM1 activation led to significant lysosomal degradation of RXRA in prediabetic and T2D models.
Enhanced insulin secretion and responsiveness were observed following SQSTM1 agonist treatment.
Findings suggest potential therapeutic avenues for managing T2D through SQSTM1 modulation.

Abstract

and mice using ATB1002, a chemical N-degron designed to bind and activate SQSTM1 as an N-recognin of the N-degron pathway. In prediabetic and T2D models, SQSTM1 agonists induced the lysosomal degradation of RXRA, and enhanced glucose-stimulated insulin secretion and insulin responsiveness. These results identify SQSTM1 as a master regulator in glucose metabolism and insulin secretion, providing a therapeutic means to treat T2D.

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Cite This Study

Jung et al. (Thu,) studied this question.

synapsesocial.com/papers/6a095a877880e6d24efe073c https://doi.org/https://doi.org/10.1080/15548627.2026.2674715

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