Selenoprotein P-Neutralizing Antibody Ameliorates Glucose Intolerance and Insulin Secretion

Selenoprotein P (SeP) is a liver-derived selenium (Se)-supply protein to maintain Se levels in peripheral tissues. The safety window of Se is narrow, even below the levels required for intoxication, supra-nutritional intake of Se has been reported to cause an increase in the risk of type 2 diabetes. Previous studies suggested that Se-supply activity of excess SeP was related to deterioration of insulin secretion and glucose metabolism. Thus, the inhibition of Se-supply via suppression of SeP binding to cells might improve insulin secretion and glucose metabolism impaired by excess SeP. We established neutralizing antibodies against human SeP. Among them, anti-human SeP monoclonal antibody (mAb) AE2 was identified to have a strong neutralizing activity, and its administration to mice significantly improved glucose intolerance and reduction of insulin secretion, which were induced by intraperitoneal administration of human SeP. In addition, mAb AE2 significantly suppressed SeP-induced impairment of insulin secretion and cell viability of insulinoma MIN6 cells. In this presentation, we will discuss a molecular basis for the development of therapeutic agents for type 2 diabetes by targeting SeP.