期刊
BIOCHEMICAL PHARMACOLOGY
卷 197, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2021.114888
关键词
Type 1 diabetes; Osteoporosis; Nitric oxide; Osteoblast; Osteoclast; PI3 kinase; cGMP signaling
资金
- Shahid Beheshti University of Medical Sciences, Tehran, Iran [28760-1]
Type 1 diabetes-induced osteoporosis is characterized by decreased bone quality and increased fracture risk. The mechanisms include insulin deficiency, high blood sugar, oxidative stress, and inflammation. Decreased nitric oxide availability plays a role in T1D-induced osteoporosis.
Type 1 diabetes (T1D)-induced osteoporosis is characterized by decreased bone mineral density, bone quality, rate of bone healing, bone formation, and increased bone resorption. Patients with T1D have a 2-7-fold higher risk of osteoporotic fracture. The mechanisms leading to increased risk of osteoporotic fracture in T1D include insulin deficiency, hyperglycemia, insulin resistance, lower insulin-like growth factor-1, hyperglycemia-induced oxidative stress, and inflammation. In addition, a higher probability of falling, kidney dysfunction, weakened vision, and neuropathy indirectly increase the risk of osteoporotic fracture in T1D patients. Decreased nitric oxide (NO) bioavailability contributes to the pathophysiology of T1D-induced osteoporotic fracture. This review discusses the role of NO in osteoblast-mediated bone formation and osteoclast-mediated bone resorption in T1D. In addition, the mechanisms involved in reduced NO bioavailability and activity in type 1 diabetic bones as well as NO-based therapy for T1D-induced osteoporosis are summarized. Available data indicates that lower NO bioavailability in diabetic bones is due to disruption of phosphatidylinositol 3-kinase/protein kinase B/endothelial NO synthases and NO/cyclic guanosine monophosphate/protein kinase G signaling pathways. Thus, NO bioavailability may be boosted directly or indirectly by NO donors. As NO donors with NO-like effects in the bone, inorganic nitrate and nitrite can potentially be used as novel therapeutic agents for T1D-induced osteoporosis. Inorganic nitrites and nitrates can decrease the risk for osteoporotic fracture probably directly by decreasing osteoclast activity, decreasing fat accumulation in the marrow cavity, increasing osteoblast activity, and increasing bone perfusion or indirectly, by improving hyperglycemia, insulin resistance, and reducing body weight.
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