Changes in microvascular density differentiate metabolic health outcomes in monkeys with prior radiation exposure and subsequent skeletal muscle ECM remodeling
| Autor: | Ian M. Williams, Tennille D. Presley, Ashley T. Davis, J. M. Cline, K. M. Fanning, Kylie Kavanagh, B. Pfisterer, David H. Wasserman |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Physiology Disease Type 2 diabetes Radiation Dosage 03 medical and health sciences In vivo Fibrosis Physiology (medical) Internal medicine Diabetes mellitus medicine Animals Muscle Skeletal Radiation Injuries Prior Radiation business.industry Microvascular Density Skeletal muscle Dose-Response Relationship Radiation Radiation Exposure medicine.disease Macaca mulatta Extracellular Matrix 030104 developmental biology Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 2 Microvessels Female Insulin Resistance business Reactive Oxygen Species Research Article |
| Zdroj: | American journal of physiology. Regulatory, integrative and comparative physiology. 313(3) |
| ISSN: | 1522-1490 |
| Popis: | Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5–9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques ( Macaca mulatta, n = 7–8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-β1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|