scholarly journals The Role of Organelle Stresses in Diabetes Mellitus and Obesity: Implication for Treatment

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Yi-Cheng Chang ◽  
Siow-Wey Hee ◽  
Meng-Lun Hsieh ◽  
Yung-Ming Jeng ◽  
Lee-Ming Chuang

The type 2 diabetes pandemic in recent decades is a huge global health threat. This pandemic is primarily attributed to the surplus of nutrients and the increased prevalence of obesity worldwide. In contrast, calorie restriction and weight reduction can drastically prevent type 2 diabetes, indicating a central role of nutrient excess in the development of diabetes. Recently, the molecular links between excessive nutrients, organelle stress, and development of metabolic disease have been extensively studied. Specifically, excessive nutrients trigger endoplasmic reticulum stress and increase the production of mitochondrial reactive oxygen species, leading to activation of stress signaling pathway, inflammatory response, lipogenesis, and pancreatic beta-cell death. Autophagy is required for clearance of hepatic lipid clearance, alleviation of pancreatic beta-cell stress, and white adipocyte differentiation. ROS scavengers, chemical chaperones, and autophagy activators have demonstrated promising effects for the treatment of insulin resistance and diabetes in preclinical models. Further results from clinical trials are eagerly awaited.

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.


Author(s):  
Piero Marchetti ◽  
Marco Bugliani ◽  
Vincenzo De Tata ◽  
Mara Suleiman ◽  
Lorella Marselli

2014 ◽  
Vol 94 (2) ◽  
pp. 186-197 ◽  
Author(s):  
Jennifer R. Kulzer ◽  
Michael L. Stitzel ◽  
Mario A. Morken ◽  
Jeroen R. Huyghe ◽  
Christian Fuchsberger ◽  
...  

2011 ◽  
Vol 8 (1) ◽  
pp. 2 ◽  
Author(s):  
Marina Casimir ◽  
Paula B de Andrade ◽  
Asllan Gjinovci ◽  
Jean-Pierre Montani ◽  
Pierre Maechler ◽  
...  

Autophagy ◽  
2009 ◽  
Vol 5 (7) ◽  
pp. 1055-1056 ◽  
Author(s):  
Piero Marchetti ◽  
Matilde Masini

Cell Calcium ◽  
2011 ◽  
Vol 50 (6) ◽  
pp. 481-490 ◽  
Author(s):  
James W. Ramadan ◽  
Stephen R. Steiner ◽  
Christina M. O’Neill ◽  
Craig S. Nunemaker

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