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      Treadmill exercise alleviates diabetic cardiomyopathy by suppressing plasminogen activator inhibitor expression and enhancing eNOS in streptozotocin-induced male diabetic rats

      research-article
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      Endocrine Connections
      Bioscientifica Ltd
      exercises, different intensity, PAI-1, nitric oxide, diabetic cardiomyopathy

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          Abstract

          Objective

          To investigate the biological mechanism of the effect of different intensity exercises on diabetic cardiomyopathy.

          Methods

          87 raise specific pathogen SPF healthy 6-week-old male Sprague–Dawley rats, fed 6 weeks with high-fat diet for rats were used, and a diabetic model was established by intraperitoneal injection of streptozotocin – randomly selected 43 rats were divided into Diabetic control group (DCG, n = 10), Diabetic exercise group 1 (DEG1, n = 11), Diabetic exercise group 2 (DEG2, n = 11) and Diabetic exercise group 3 (DEG3, n = 11). The rats in DEG1 were forced to run on a motorized treadmill, the exercise load consisted of running at a speed of 10 m/min, the exercise load of the rats in DEG2 were running at a speed of 15 m/min, the exercise load of the rats in DEG3 were running at a speed of 20 m/min, for one hour once a day for 6 weeks. After 6 weeks of exercise intervention, glucose metabolism-related indexes in rats such as blood glucose (FBG), glycosylated serum protein (GSP) and insulin (FINS); cardiac fibrinolytic system parameters such as PAI-1 (plasminogen activator inhibitor 1), Von Willebrand factor (vWF), protein kinase C (PKC) and diacylglycerol (DAG); and serum level of NO, eNOS and T-NOS were measured.

          Result

          Compared with DCG, fasting blood glucose and GSP were decreased, while insulin sensitivity index and insulin level were increased in all rats of the three exercise groups. FBG decrease was statistically significant ( P < 0.01), only GSP decrease was statistically significant ( P < 0.05) in DEG1 and DEG2, PAI-1 in three exercise groups were significantly reduced ( P < 0.05), plasma vWF levels in the three exercise groups were significantly lower than those in the DCG group ( P < 0.01); PKC levels decreased dramatically in the three exercise groups and DAG levels decrease slightly ( P < 0.05), but with no significant difference. Compared with DCG, the serum level of NO was significantly higher ( P < 0.05), and eNOS level was significantly elevated ( P < 0.05). T-NOS elevation was statistically significant in DEG1 ( P < 0.05).

          Conclusions

          Low- and moderate-intensity exercise can better control blood glucose level in diabetic rats; myocardial PAI-1 in DEG1, DEG2 and DEG3 rats decreased significantly ( P < 0.05), serum NO increased ( P < 0.05) and eNOS increased ( P < 0.05) significantly. Therefore, it is inferred that exercise improves the biological mechanism of diabetic cardiomyopathy by affecting the levels of PAI-1 and eNOS, and there is a dependence on intensity.

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          Most cited references37

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          Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis.

          Observational studies have suggested an association between active smoking and the incidence of type 2 diabetes. To conduct a systematic review with meta-analysis of studies assessing the association between active smoking and incidence of type 2 diabetes. A search of MEDLINE (1966 to May 2007) and EMBASE (1980 to May 2007) databases was supplemented by manual searches of bibliographies of key retrieved articles, reviews of abstracts from scientific meetings, and contact with experts. Studies were included if they reported risk of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes in relationship to smoking status at baseline; had a cohort design; and excluded persons with diabetes at baseline. Two authors independently extracted the data, including the presence or absence of active smoking at baseline, the risk of diabetes, methods used to detect diabetes, and key criteria of study quality. Relative risks (RRs) were pooled using a random-effects model. Associations were tested in subgroups representing different patient characteristics and study quality criteria. The search yielded 25 prospective cohort studies (N = 1.2 million participants) that reported 45 844 incident cases of diabetes during a study follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported adjusted RRs greater than 1 (range for all studies, 0.82-3.74). The pooled adjusted RR was 1.44 (95% confidence interval [CI], 1.31-1.58). Results were consistent and statistically significant in all subgroups. The risk of diabetes was greater for heavy smokers (> or =20 cigarettes/day; RR, 1.61; 95% CI, 1.43-1.80) than for lighter smokers (RR,1.29; 95% CI, 1.13-1.48) and lower for former smokers (RR, 1.23; 95% CI, 1.14-1.33) compared with active smokers, consistent with a dose-response phenomenon. Active smoking is associated with an increased risk of type 2 diabetes. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.
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            Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study.

            Elevated serum levels of acute-phase proteins, indicating chronic subclinical inflammation, have been associated with cardiovascular disease as well as the insulin resistance syndrome. Chronic inflammation may also be a risk factor for developing type 2 diabetes. We studied the concentrations of C-reactive protein (CRP), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) in 1,047 nondiabetic subjects in relation to incident diabetes within 5 years in the Insulin Resistance Atherosclerosis Study. Subjects with diabetes at follow-up (n = 144) had higher baseline levels of fibrinogen (mean +/- SD; 287.8 +/- 58.8 vs. 275.1 +/- 56.0 mg/dl; P = 0.013) as well as of CRP (median [interquartile range]; 2.40 [1.29, 5.87] vs. 1.67 mg/l [0.75, 3.41]; P = 0.0001) and PAI-1 (24 [15, 37.5] vs. 16 ng/ml [9, 27]; P = 0.0001) than nonconverters. The odds ratio (OR) of converting to diabetes was significantly increased with increasing baseline concentrations of the inflammatory markers. In contrast to PAI-1, the association of CRP and fibrinogen with incident diabetes was significantly attenuated after adjustment for body fat (BMI or waist circumference) or insulin sensitivity (S(I)), as assessed by a frequently sampled intravenous glucose tolerance test. In a logistic regression model that included age, sex, ethnicity, clinical center, smoking, BMI, S(I), physical activity, and family history of diabetes, PAI-1 still remained significantly related to incident type 2 diabetes (OR [95% CI] for 1 SD increase: 1.61 [1.20-2.16]; P = 0.002). Chronic inflammation emerges as a new risk factor for the development of type 2 diabetes; PAI-1 predicts type 2 diabetes independent of insulin resistance and other known risk factors for diabetes.
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              Adiponectin and protection against type 2 diabetes mellitus.

              Adiponectin is an adipocyte-derived peptide, which has anti-inflammatory and insulin-sensitising properties. We designed a nested case-control study to assess whether baseline adiponectin concentrations in plasma are independently associated with risk of type 2 diabetes. We found that adiponectin concentrations in plasma were lower among individuals who later developed type 2 diabetes than among controls (mean 5.34 microg/mL [SD 3.49] vs 6.87 microg/mL [4.58], p<0.0001). High concentrations of adiponectin were associated with a substantially reduced relative risk of type 2 diabetes after adjustment for age, sex, waist-to-hip ratio, body-mass index, smoking, exercise, alcohol consumption, education, and glycosylated haemoglobin A(1c) (odds ratio 4th vs 1st quartile 0.3 [95% CI 0.2-0.7], p=0.0051). We conclude that adiponectin is independently associated with a reduced risk of type 2 diabetes in apparently healthy individuals.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                April 2018
                19 March 2018
                : 7
                : 4
                : 553-559
                Affiliations
                [1]College of Physical Education Chaohu University, Anhui Province, China
                Author notes
                Correspondence should be addressed to F Xianjin: shenxiazhao@ 123456126.com
                Article
                EC180060
                10.1530/EC-18-0060
                5887130
                29555653
                ab84e9e3-5f9c-4b03-8447-5521dcfcca8d
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 12 February 2018
                : 19 March 2018
                Categories
                Research

                exercises,different intensity,pai-1,nitric oxide,diabetic cardiomyopathy

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