Heterozygous Inactivation of the Na/Ca Exchanger Increases Glucose-Induced Insulin Release, b-Cell Proliferation, and Mass

OBJECTIVE—We have previously shown that overexpression of the Na-Ca exchanger (NCX1), a protein responsible for Ca2+ extrusion from cells, increases b-cell programmed cell death (ap-optosis) and reduces b-cell proliferation. To further characterize the role of NCX1 in b-cells under in vivo conditions, we devel-oped and characterized mice deficient for NCX1. RESEARCH DESIGN AND METHODS—Biologic and morpho-logic methods (Ca2+ imaging, Ca2+ uptake, glucose metabolism, insulin release, and point counting morphometry) were used to assess b-cell function in vitro. Blood glucose and insulin levels were measured to assess glucose metabolism and insulin sensi-tivity in vivo. Islets were transplanted under the kidney capsule to assess their performance to revert diabetes in alloxan-diabetic mice. RESULTS—Heterozygous inactivation of Ncx1 in mice induce