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Apelin Gene Therapy Increases Autophagy via Activation of Sirtuin 3 in Diabetic Heart. Apelin基因治疗通过激活Sirtuin 3增加糖尿病心脏的自噬。

Diabetes research (Fairfax, Va.) Pub Date : 2015-10-01 Epub Date: 2015-08-21 DOI: 10.17140/DROJ-1-115

Xuwei Hou, Heng Zeng, Qin-Hui Tuo, Daun-Fang Liao, Jian-Xiong Chen

{"title":"Apelin Gene Therapy Increases Autophagy via Activation of Sirtuin 3 in Diabetic Heart.","authors":"Xuwei Hou, Heng Zeng, Qin-Hui Tuo, Daun-Fang Liao, Jian-Xiong Chen","doi":"10.17140/DROJ-1-115","DOIUrl":"https://doi.org/10.17140/DROJ-1-115","url":null,"abstract":"Heart failure is the leading cause of death in diabetic patients. Recently we showed that apelin gene therapy attenuates heart failure following myocardial infarction. This study further explored the potential mechanisms by which apelin may reduce cardiac injury in Postmyocardial infarction (MI)) model of diabetes. Wild type and Sirt3 knockout (Sirt3 KO) mice were induced into diabetes by intra-peritoneal (i.p.) Streptozotocin (STZ). STZ mice were then subjected to MI followed by immediate intramyocardial injection with Adenovirus-apelin (Ad-apelin). Ad-apelin treatment resulted in over expression of apelin in the ischemic hearts of STZ mice. Apelin over expression led to a significant increase in Sirt3 expression. Apelin over expression significantly reduced gp91phox expression. This was accompanied by a significant reduction of reactive oxygen species formation. Ad-apelin treatment also dramatically reduced NF-κb-p65 expression in WT-STZ mice. Over expression of apelin further enhanced autophagy markers (LC3-II and beclin-1) expression in post-MI heart. Most intriguingly, knockout of Sirt3 in STZ mice abolished these beneficial effects of apelin treatment. In vitro, knockout of Sirt3 in EPCs significantly enhanced high glucose-induced ROS formation. Conversely, treatment of Sirt3 KO-EPCs with NADPH oxidase inhibitor led to two fold increase in LC3-II levels. Our studies demonstrate that apelin increases autophagy via up regulation of Sirt3 and suppression of ROS-NF-κb pathway in diabetic heart.","PeriodicalId":91862,"journal":{"name":"Diabetes research (Fairfax, Va.)","volume":"1 4","pages":"84-91"},"PeriodicalIF":0.0,"publicationDate":"2015-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35277605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Inverse Association between Vitamin D Status and Diabetes in a Clinic Based Sample of Hispanic Adults in Puerto Rico. 波多黎各西班牙裔成人临床样本中维生素D水平与糖尿病的负相关

Diabetes research (Fairfax, Va.) Pub Date : 2015-04-01 Epub Date: 2015-01-21 DOI: 10.17140/DROJ-1-102

Grisel Ramos-Trautmann, Lilliana González, Giselle Díaz-Luquis, Cynthia M Pérez, Cristina Palacios

{"title":"Inverse Association between Vitamin D Status and Diabetes in a Clinic Based Sample of Hispanic Adults in Puerto Rico.","authors":"Grisel Ramos-Trautmann, Lilliana González, Giselle Díaz-Luquis, Cynthia M Pérez, Cristina Palacios","doi":"10.17140/DROJ-1-102","DOIUrl":"https://doi.org/10.17140/DROJ-1-102","url":null,"abstract":"Background: Vitamin D deficiency is a public health problem around the world. Diabetes has been associated with vitamin D deficiency. We aimed to examine the association between the vitamin D status and diabetes in a clinic based sample of Hispanic adults in Puerto Rico.Methods: Demographics and laboratory test results for serum 25(OH)D, Fasting Blood Glucose (FBG), and Haemoglobin A1C (HbAlc) were extracted from medical records. Vitamin D status was classified as deficient (<12 ng/ml); inadequate (12-20 ng/ml); insufficient (21-29 ng/ml) and optimal (≥30 ng/ml) using serum 25(OH)D levels.Results: A total of 716 records were included in the analyses. Most were females (63.3%), with mean age of 54.1±14.9 y, mean BMI 30.1±6.3 kg/m2 and mean serum 25(OH)D levels of 24.3±8.6 ng/ml. Most were classified as diabetics (41.1%). Those with diabetes had lower 25(OH)D levels compared to pre-diabetic and normal glucose status (p<0.05). Serum 25(OH) D levels were inversely correlated to FBG and HbA1c in the total sample and in men (p<0.05). After adjusting for age, gender, BMI and seasonality, there was a greater risk of diabetes, but not prediabetes, in those with serum 25(OH)D levels <30 ng/ml. This risk increased from 1.8 times in those with vitamin D insufficiency to 4.2 times in those with vitamin D deficiency (<12 ng/ml).Conclusion: Diabetes risk significantly increased as serum 25(OH)D levels decreased in this group of Hispanic adults, underscoring the importance of routinely screening high risk individuals for vitamin D deficiency and offer supplementation to normalize serum levels.","PeriodicalId":91862,"journal":{"name":"Diabetes research (Fairfax, Va.)","volume":"1 1","pages":"5-11"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365235/pdf/nihms849883.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34856937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

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