Thrombospondin-1: An Islet Endothelial Cell Signal of Importance for b-Cell Function

islets has been shown to cause islet hyperplasia. This study tested the hypothesis that endothelial-derived TSP-1 is important for b-cell function. RESEARCH DESIGN AND METHODS—Islet function was evaluated both in vivo and in vitro. Messenger RNA and protein expression were measured by real-time PCR and Western blot, respectively. The role of endothelial-derived TSP-1 for b-cell func-tion was determined using a transplantation design in which re-cipient blood vessels either were allowed to grow or not into the transplanted islets. RESULTS—TSP-1–deficient mice were glucose intolerant, de-spite having an increased b-cell mass. Moreover, their islets had decreased glucose-stimulated insulin release, (pro)insulin bio-synthesis, and glucose oxidation rate, as well as increased ex-pression of uncoupling protein-2 and lactate dehydrogenase-