Glucose-mediated insulin secretion is improved in FHL2-deficient mice and elevated FHL2 expression in humans is associated with type 2 diabetes – published online 08/07/2022

Jayron J. Habibe, Maria P. Clemente-Olivo, Torsten P. M. Scheithauer, Elena Rampanelli, Hilde Herrema, Mariska Vos, Arnout Mieremet, Max Nieuwdorp, Daniel H. van Raalte, Etto C. Eringa, Carlie J. M. de Vries

FHL2, the gene encoding the four and a half LIM domains 2 (FHL2) protein, contains DNA methylation marks, which forensic studies have consistently found to be correlated with the age of an individual. Hypermethylation of these CpG loci causes an increase in FHL2 expression. In this issue, Habibe and Clemente-Olivo et al (https://doi.org/10.1007/s00125-022-05750-1) show that individuals with type 2 diabetes also express higher FHL2 levels in their pancreatic islets compared with healthy individuals. Furthermore, the authors demonstrate that, compared with their wild-type littermates, Fhl2-deficient mice clear glucose faster, whereas insulin sensitivity is similar for both strains of mice. Isolated pancreatic islets from mice that are deficient for Fhl2 show increased glucose-induced insulin secretion, which the authors suggest may be explained, at least partially, by enhanced expression of the glucose-transporter GLUT2. In line with this, FHL2 gain of function is detrimental to insulin secretion of cultured beta cells due to a reduced uptake of glucose and enhanced levels of reactive oxygen species. The authors conclude that inhibition of FHL2 in human transplant islets may improve transplant function in vivo.

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