1. Cartilage Oligomeric Matrix Protein–Angiopoientin-1 Enhances Angiogenesis of Isolated Islet and Maintains Normoglycemia Following Transplantation
- Author
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Choon Hyuck David Kwon, Jae-Won Joh, E. Y. Shim, Gou Young Koh, C. Moon, S. J. Kim, K. S. Park, B. K. Choi, Y. S. Kim, and S. H. Kim
- Subjects
Blood Glucose ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Angiogenesis ,Recombinant Fusion Proteins ,Islets of Langerhans Transplantation ,Neovascularization, Physiologic ,Diabetes Mellitus, Experimental ,Neovascularization ,Mice ,Reference Values ,Internal medicine ,Angiopoietin-1 ,medicine ,Animals ,Humans ,Cartilage oligomeric matrix protein ,Transplantation ,Glucose tolerance test ,geography ,geography.geographical_feature_category ,medicine.diagnostic_test ,biology ,business.industry ,Pancreatic islets ,Genetic Variation ,Glucose Tolerance Test ,Islet ,Streptozotocin ,Diabetes Mellitus, Type 1 ,Endocrinology ,medicine.anatomical_structure ,biology.protein ,Surgery ,medicine.symptom ,business ,medicine.drug - Abstract
Islet transplantation (ITx) has potential as a therapy for patients with type 1 diabetes. For successful engraftment and insulin independence, the transplanted islets must establish an adequate, stable blood supply. Angiopoientin-1 (Ang1) is a specific growth factor that induces vascularization via the Tie2 or Tie1 receptor. In this study, we used an in vitro angiogenesis assay to evaluate islet function following transplantation and the effect of the Ang1 variant cartilage oligomeric matrix protein (COMP) Ang1 on isolated islets. The enhanced function of islets transduced with COMP-Ang1 was also confirmed in a streptozotocin (STZ)-induced diabetic mice model. In a three-dimensional collagen-based culture system, the transduction of COMP-Ang1 into islets significantly increased angiogenesis compared with the bacterial-β-galactosidase (LacZ)-transduced controls and an intact, nontransduced islet negative control group. COMP-Ang1 transduced islets also attenuated hyperglycemia in syngeneic diabetic C57BL/6 mice and enhanced glucose tolerance by areas under the curves of intraperitoneal glucose tolerance tests. These findings demonstrated the capacity of COMP-Ang1 to promote revascularization in cultured islets, which may contribute to successful transplantation in vivo.
- Published
- 2010
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