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10.1105/tpc.010538 102 PnueliL.LiangH.RozenbergM.MittlerR

In T2D mouse models, sex-specific differences in GPER expression were observed, with female mice exhibiting significantly higher levels of GPER expression than male mice, while GPER expression decreased significantly following the induction of diabetes, implying that GPER expression influences the occurrence and development of diabetes

The total human evidence base, as of this writing, consists of the following: 1) a Phase I safety trial of 42 healthy volunteers that was registered in 2015, canceled in 2016, and never published, 2) a retrospective case series of 12 patients with knee pain, no control group, and no validated outcome measure, and 3) a 2025 pilot safety study involving two healthy adults who received intravenous infusions at a single private clinic in Florida

While higher doses may be used short-term, long-term mega-dosing offers no added benefit and may cause mild digestive discomfort in some people