Phlda3 regulates beta cell survival during stress.
Mohammed Bensellam, Jeng Yie Chan, Kailun Lee, Mugdha V Joglekar, Anandwardhan A Hardikar, Thomas Loudovaris, Helen E Thomas, Jean-Christophe Jonas, D Ross Laybutt
Sci Rep | Published : 2019
The loss of functional beta cell mass characterises all forms of diabetes. Beta cells are highly susceptible to stress, including cytokine, endoplasmic reticulum (ER) and oxidative stress. This study examined the role of pleckstrin homology-like, domain family A, member 3 (Phlda3) in beta cell survival under stress conditions and the regulatory basis. We found that the mRNA levels of Phlda3 were markedly upregulated in vivo in the islets of diabetic humans and mice. In vitro, exposure of MIN6 cells or islets to cytokines, palmitate, thapsigargin or ribose upregulated Phlda3 mRNA and protein levels, concurrent with the induction of ER stress (Ddit3 and Trb3) and antioxidant (Hmox1) genes. Fur..View full abstract