miR-149-5p protects against high glucose-induced pancreatic beta cell apoptosis via targeting the BH3-only protein BIM

2019 ◽  
Vol 110 ◽  
pp. 104279 ◽  
Author(s):  
Dongyun Ruan ◽  
Yanfeng Liu ◽  
Xiaoqing Wang ◽  
Dahao Yang ◽  
Yan Sun
2009 ◽  
Vol 41 (4) ◽  
pp. 879-890 ◽  
Author(s):  
Xiuli Men ◽  
Haiyan Wang ◽  
Mi Li ◽  
Hanqing Cai ◽  
Shiqin Xu ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (1) ◽  
pp. e0116972 ◽  
Author(s):  
Minjeong Jung ◽  
Jaemeun Lee ◽  
Hye-Young Seo ◽  
Ji Sun Lim ◽  
Eun-Kyoung Kim

Author(s):  
Eva Decroli ◽  
Asman Manaf ◽  
Syafril Syahbuddin ◽  
Sarwono Waspadji ◽  
Dwisari Dillasamola

Objective: This study aimed to reveal differences in levels of survivin and Raf-1 kinase in prediabetes, controlled Type 2 diabetes mellitus (T2DM), uncontrolled T2DM, and their relationship with hemoglobin A1c (HbA1c) levels and serum triglyceride levels.Methods: This study was an observational study with a cross-sectional design. The study involved 60 people with T2DM who visited the endocrine and metabolic clinic and 30 prediabetes patients. The variables were survivin levels and Raf-1 kinase enzymes that examined using enzyme-linked immunosorbent assay techniques. HbA1c values are measured by high-performance liquid chromatography and triglyceride levels measured by enzymatic method.Results: Average levels of Raf-1 kinase were significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (11.6±1.4 pg mL, 9.9±1.1 pg/mL, and 9.1±1.5 pg/mL). Survivin was significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (5.4±0.4 pg mL, 5.0±0.2 pg/mL, and 4.7±0.1 pg/mL). There was no correlation between HbA1c with Raf-1 kinase levels (R=−0.215, p=0.250), but there was a correlation between HbA1c with serum survivin levels (R=−0.6, *p<0.05). There was a correlation between the levels of triglycerides with survivin but not with Raf-1 kinase (R=−0.267, *p=0.039).Conclusion: Survivin and Raf-1 kinase levels are lower in uncontrolled T2DM. This explained the role of survivin and Raf-1 kinase against enhancement of pancreatic beta-cell apoptosis in patients with T2DM.


2010 ◽  
Vol 285 (44) ◽  
pp. 33623-33631 ◽  
Author(s):  
Nadeeja Wijesekara ◽  
Mansa Krishnamurthy ◽  
Alpana Bhattacharjee ◽  
Aamir Suhail ◽  
Gary Sweeney ◽  
...  

PLoS Genetics ◽  
2013 ◽  
Vol 9 (5) ◽  
pp. e1003532 ◽  
Author(s):  
Tatiane C. Nogueira ◽  
Flavia M. Paula ◽  
Olatz Villate ◽  
Maikel L. Colli ◽  
Rodrigo F. Moura ◽  
...  

2020 ◽  
Author(s):  
Halesha D. Basavarajappa ◽  
Jose M. Irimia ◽  
Patrick T. Fueger

AbstractAvoiding loss of functional beta cell mass is critical for preventing or treating diabetes. Currently, the molecular mechanisms underlying beta cell death are partially understood, and there is a need to identify new targets for developing novel therapeutics to treat diabetes. Previously, our group established that Mig6, an inhibitor of EGF signaling, mediates beta cell death under diabetogenic conditions. The objective of this study was to clarify the mechanisms linking diabetogenic stimuli to beta cell death by investigating Mig6-interacting proteins. Using co-immunoprecipitation and mass spectrometry, we evaluated the binding partners of Mig6 under both normal glucose (NG) and glucolipotoxic (GLT) conditions in beta cells. We identified that Mig6 interacts dynamically with NumbL; whereas Mig6 associates with NumbL under NG, this interaction is disrupted under GLT conditions. Further, we demonstrate that siRNA-mediated suppression of NumbL expression in beta cells prevented apoptosis under GLT conditions by blocking activation of NF-κB signaling. Using co-immunoprecipitation experiments we observed that NumbL’s interactions with TRAF6, a key component of NFκB signaling, are increased under GLT conditions. The interactions among Mig6, NumbL, and TRAF6 are dynamic and context-dependent. We propose a model wherein these interactions activate pro-apoptotic NF-κB signaling while blocking pro-survival EGF signaling under diabetogenic conditions, leading to beta cell apoptosis. These findings indicate that NumbL should be further investigated as a candidate anti-diabetic therapeutic target.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2036-P
Author(s):  
VINNY NEGI ◽  
JEONGKYUNG K. LEE ◽  
RUYA LIU ◽  
RAJAGANAPATI JAGANNATHAN ◽  
FENG LI ◽  
...  

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