Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic autonomic neuropathy (DAN) commonly complicates diabetes and is associated with increased mortality rates over 5 yr. This fact denotes the significance of DAN prevention, mainly with effective glycemic control. However, total prevention of autonomic neuropathy in diabetic patients is not achievable. Thus, the timely detection of DAN and the use of effective means to improve autonomic nervous system function or slow down its progression become of utmost significance. Heart rate variability (HRV) is a technique that measures the beat-to-beat variability in RR intervals, which reflects changes in autonomic activity and their impact on cardiovascular function. Circadian variation in time and frequency domains of heart variability has been shown to correlate with circadian rhythm of ambulatory ischemia and suggests that relative changes in vagal and sympathetic tone at different times during the day may have a direct relationship to the severity of clinical events. Forty-seven (21 boys and 26 girls) type I insulin-dependent diabetics and 46 control subjects (19 boys and 27 girls) were included in the study. Our investigation demonstrated that overall HRV is markedly depressed in diabetes mellitus (DM). All time domain parameters except standard deviation of all 5-min mean RR intervals and all frequency domain indices maintain significant circadian variation. These changes in overall HRV and HRV circadian rhythms reflect significant reductions in cardiac parasympathetic activity and, possibly, increased sympathetic tone.
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PMID:Heart rate variability and circadian variations in type 1 diabetes mellitus. 1648 74

Diabetes compromises the bone marrow (BM) microenvironment and reduces the number of circulating CD34(+) cells. Diabetic autonomic neuropathy (DAN) may impact the BM, because the sympathetic nervous system is prominently involved in BM stem cell trafficking. We hypothesize that neuropathy of the BM affects stem cell mobilization and vascular recovery after ischemia in patients with diabetes. We report that, in patients, cardiovascular DAN was associated with fewer circulating CD34(+) cells. Experimental diabetes (streptozotocin-induced and ob/ob mice) or chemical sympathectomy in mice resulted in BM autonomic neuropathy, impaired Lin(-)cKit(+)Sca1(+) (LKS) cell and endothelial progenitor cell (EPC; CD34(+)Flk1(+)) mobilization, and vascular recovery after ischemia. DAN increased the expression of the 66-kDa protein from the src homology and collagen homology domain (p66Shc) and reduced the expression of sirtuin 1 (Sirt1) in mice and humans. p66Shc knockout (KO) in diabetic mice prevented DAN in the BM, and rescued defective LKS cell and EPC mobilization. Hematopoietic Sirt1 KO mimicked the diabetic mobilization defect, whereas hematopoietic Sirt1 overexpression in diabetes rescued defective mobilization and vascular repair. Through p66Shc and Sirt1, diabetes and sympathectomy elevated the expression of various adhesion molecules, including CD62L. CD62L KO partially rescued the defective stem/progenitor cell mobilization. In conclusion, autonomic neuropathy in the BM impairs stem cell mobilization in diabetes with dysregulation of the life-span regulators p66Shc and Sirt1.
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PMID:Diabetes causes bone marrow autonomic neuropathy and impairs stem cell mobilization via dysregulated p66Shc and Sirt1. 2465 1