| First Author | Olerud J | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 7 | Pages | 1946-54 |
| PubMed ID | 21617177 | Mgi Jnum | J:186751 |
| Mgi Id | MGI:5433005 | Doi | 10.2337/db10-0277 |
| Citation | Olerud J, et al. (2011) Thrombospondin-1: an islet endothelial cell signal of importance for beta-cell function. Diabetes 60(7):1946-54 |
| abstractText | OBJECTIVE: Loss of thrombospondin (TSP)-1 in pancreatic islets has been shown to cause islet hyperplasia. This study tested the hypothesis that endothelial-derived TSP-1 is important for beta-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 beta-cell function was determined using a transplantation design in which recipient blood vessels either were allowed to grow or not into the transplanted islets. RESULTS: TSP-1-deficient mice were glucose intolerant, despite having an increased beta-cell mass. Moreover, their islets had decreased glucose-stimulated insulin release, (pro)insulin biosynthesis, and glucose oxidation rate, as well as increased expression of uncoupling protein-2 and lactate dehydrogenase-A when compared with control islets. Almost all TSP-1 in normal islets were found to be derived from the endothelium. Transplantation of free and encapsulated neonatal wild-type and TSP-1-deficient islets was performed in order to selectively reconstitute with TSP-1-positive or -negative blood vessels in the islets and supported that the beta-cell defects occurring in TSP-1-deficient islets reflected postnatal loss of the glycoprotein in the islet endothelial cells. Treatment of neonatal TSP-1-deficient mice with the transforming growth factor (TGF)beta-1-activating sequence of TSP-1 showed that reconstitution of TGFbeta-1 activation prevented the development of decreased glucose tolerance in these mice. Thus, endothelial-derived TSP-1 activates islet TGFbeta-1 of importance for beta-cells. CONCLUSIONS: Our study indicates a novel role for endothelial cells as functional paracrine support for pancreatic beta-cells. |
