Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice
| Autor: | Johan Olerud, Per-Ola Carlsson, Gustav Christoffersson, Hanna Emanuelsson, Carl Johan Drott |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Aging Medicin och hälsovetenskap Anatomy and Physiology Mouse Angiogenesis medicine.medical_treatment Islets of Langerhans Transplantation lcsh:Medicine Cardiovascular Medical and Health Sciences Thrombospondin 1 Mice Endocrinology immune system diseases Insulin lcsh:Science Mice Knockout Glucose tolerance test Multidisciplinary geography.geographical_feature_category medicine.diagnostic_test Age Factors virus diseases Animal Models Islet medicine.anatomical_structure Medicine Female Pancreas Research Article Adult medicine.medical_specialty endocrine system Endocrine System Paracrine Mechanisms Biology Islets of Langerhans Model Organisms Vascular Biology Internal medicine medicine Animals Humans Endocrine system Diabetic Endocrinology geography Endocrine Physiology lcsh:R Diabetes Mellitus Type 2 Glucose Tolerance Test Transplantation Glucose lcsh:Q Endocrine Cells |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 10, p e47451 (2012) |
| Popis: | Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1), that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10-12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10-12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10-12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only similar to 15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life. |
| Databáze: | OpenAIRE |
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