Complement C3 promotes islet β-cell dedifferentiation by activating Wnt/β-catenin pathway.

ABSTRACT: Islet β-cell dedifferentiation is a key step in the progression of diabetes, and complement C3 enhances secretion of several inflammatory mediators and cytokines in type 2 diabetes mellitus (T2DM). Here, we identified the underlying mechanisms of complement C3 in islet β-cell dedifferentiation. The protein level of C3 is increased in blood of T2DM patients and mice, as well as in T2DM islet β cells. Insulin, gliclazide, and metformin decreased complement C3, Nga3, and Oct4 levels but increased Pdx1 and MafA expressions; these treatments inhibit islet β-cell dedifferentiation in in vitro and in vivo models. We also observed that C3 promoted islet β-cell dedifferentiation, whereas C3 knockdown inhibited β-cell dedifferentiation. Moreover, C3 activates Wnt/β-catenin pathway by u

SUBMITTER: Zhuang L 

PROVIDER: S-EPMC11615230 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature