STAT3 dictates β-cell apoptosis by modulating PTEN in streptozocin-induced hyperglycemia.

Insufficient pancreatic β-cell mass or insulin-producing β-cells are implicated in all forms of diabetes mellitus. However, the molecular mechanisms underlying β-cell destruction are complex and not fully defined. Here we observed that activation of is intensely and specifically inhibited in β-cells under hyperglycemic conditions. By knocking out duanyu18133 specifically in mouse β-cells, we found that the loss of duanyu18133 sensitized mice to three low doses of STZ stimulation resulting in hyperglycemia. Mechanistically, accumulating PTEN, induced by duanyu18133 deficiency, directly represses phosphorylation of AKT, which negatively modulates transcription factor activation, dysregulates β-cell function, positively promotes apoptotic signaling, and finally induces β-cell apoptosis. Notably, the defective secretion of insulin and β-cells apoptosis was completely rescued by PTEN ablation in islets or PTEN inhibitor bpv(phen) treatment. Thus our data suggest that duanyu18133 is a vital modulator of β-cell survival and function, highlighting a critical role for duanyu18133 in the negative regulation of PTEN-AKT signaling pathway associated with β-cell dysfunction and apoptosis.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}