Diabetes research (Fairfax, Va.)最新文献

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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

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 gp91^phox 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.

心力衰竭是糖尿病患者死亡的主要原因。最近，我们发现apelin基因治疗可以减轻心肌梗死后的心力衰竭。本研究进一步探讨了apelin减轻糖尿病心肌梗死后(MI)模型心肌损伤的可能机制。野生型和Sirt3敲除(Sirt3 KO)小鼠经腹腔注射诱导成糖尿病。链脲霉素(STZ)。STZ小鼠在心肌内立即注射腺病毒-apelin (Ad-apelin)后进行心肌梗死。Ad-apelin处理导致STZ小鼠缺血心脏中apelin过表达。Apelin过表达导致Sirt3表达显著升高。过表达Apelin显著降低gp91phox的表达。这伴随着活性氧形成的显著减少。Ad-apelin也能显著降低WT-STZ小鼠NF-κb-p65的表达。过表达apelin进一步增强心肌梗死后心脏自噬标志物(LC3-II和beclin-1)的表达。最有趣的是，STZ小鼠的Sirt3敲除消除了apelin治疗的这些有益作用。在体外实验中，敲除EPCs中的Sirt3可显著增强高糖诱导的ROS形成。相反，用NADPH氧化酶抑制剂处理Sirt3 KO-EPCs导致LC3-II水平增加两倍。我们的研究表明，apelin通过上调Sirt3和抑制ROS-NF-κb通路来增加糖尿病心脏的自噬。

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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

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.

背景:维生素D缺乏症是一个全球性的公共卫生问题。糖尿病与维生素D缺乏有关。我们的目的是在波多黎各的西班牙裔成年人的临床样本中检查维生素D状态和糖尿病之间的关系。方法:从病历中提取血清25(OH)D、空腹血糖(FBG)和血红蛋白A1C (HbAlc)的人口统计学和实验室检测结果。维生素D状态被归类为缺乏(结果:共有716份记录被纳入分析。女性居多(63.3%)，平均年龄54.1±14.9岁，平均BMI为30.1±6.3 kg/m2，平均血清25(OH)D水平为24.3±8.6 ng/ml。其中大部分为糖尿病患者(41.1%)。与糖尿病前期和正常血糖水平相比，糖尿病患者的25(OH)D水平较低。结论:在这组西班牙裔成年人中，随着血清25(OH)D水平的降低，糖尿病风险显著增加，强调了常规筛查维生素D缺乏症高风险个体并提供补充以使血清水平正常化的重要性。

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引用次数: 6

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