Aged islets are refractory to Nkx6.1 mediated β‐cell proliferation

Abstract

Type 1 and Type 2 diabetes ultimately end in β‐cell loss. Islet transplantation could have widespread use in order to restore a diabetic patients functional β‐cell mass. A major impediment is the availability of transplant ready islets, therefore manipulation of molecular pathways that permit β‐cell expansion are critical to wider use of this treatment. As most islets available for transplant will be from aged donors, the ability to manipulate functional β‐cell mass must be applicable to islets from aged sources. We have demonstrated that expression of Nkx6.1 in islets isolated from young rats can enhance β‐cell proliferation, function and survival. Interestingly, islets isolated from aged rats are refractory to Nkx6.1 mediated enhancement. Here we present data characterizing the differences between aged and young islets in terms of morphology, islet mass, insulin secretion, transcriptome and function of Nkx6.1 overexpression. Our data demonstrate that aged β‐cells are significantly different from young β‐cells, and suggest potential applications to expanding β‐cell mass ex vivo for islet transplantation.