Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models

• DOI: 10.1038/s41467-017-01863-z
• Publication Date: 2017-11-15T19:48:19Z
• Authors: Yuichiro Mita; Kaho Nakayama; Shogo Inari; Yukina Nishito; Yuya Yoshioka; Naoko Sakai; Kanade Sotani; Takahiro Nagamura; Yuki Kuzuhara; Kumi Inagaki; Miki Iwasaki; Hirofumi Misu; Masaya Ikegawa; Toshinari Takamura; Noriko Noguchi; Yoshiro Saito
• Keywords: Selenoprotein P; Polyclonal antibodies

Selenoprotein P (SeP) functions as a selenium (Se)-supply protein. SeP is identified hepatokine, promoting insulin resistance in type 2 diabetes. Thus, the suppression of Se-supply activity might improve glucose metabolism. Here, we develop an anti-human monoclonal antibody AE2 with neutralizing against SeP. Administration to mice significantly improves intolerance and that are induced by human administration. Furthermore, excess administration decreases pancreas levels high glucose-induced secretion, which improved Epitope mapping reveals recognizes region adjacent first histidine-rich (FHR). A polyclonal mouse FHR secretion model This report describes novel molecular strategy for development diabetes therapeutics targeting