The molecular mechanisms of pancreatic β-cell glucotoxicity: Recent findings and future research directions

2012 ◽  
Vol 364 (1-2) ◽  
pp. 1-27 ◽  
Author(s):  
Mohammed Bensellam ◽  
D. Ross Laybutt ◽  
Jean-Christophe Jonas
2013 ◽  
Vol 394 (7) ◽  
pp. 909-918 ◽  
Author(s):  
Srividya Vasu ◽  
Neville H. McClenaghan ◽  
Jane T. McCluskey ◽  
Peter R. Flatt

Abstract The novel insulin-secreting human pancreatic β-cell line, 1.1B4, demonstrates stability in culture and many of the secretory functional attributes of human pancreatic β-cells. This study investigated the cellular responses of 1.1B4 cells to lipotoxicity. Chronic 18-h exposure of 1.1B4 cells to 0.5 mm palmitate resulted in decreased cell viability and insulin content. Secretory responses to classical insulinotropic agents and cellular Ca2+ handling were also impaired. Palmitate decreased glucokinase activity and mRNA expression of genes involved in secretory function but up-regulated mRNA expression of HSPA5, EIF2A, and EIF2AK3, implicating activation of the endoplasmic reticulum stress response. Palmitate also induced DNA damage and apoptosis of 1.1B4 cells. These responses were accompanied by increased gene expression of the antioxidant enzymes SOD1, SOD2, CAT and GPX1. This study details molecular mechanisms underlying lipotoxicity in 1.1B4 cells and indicates the potential value of the novel β-cell line for future research.


2009 ◽  
Vol 24 (9) ◽  
pp. 1064-1084 ◽  
Author(s):  
Michael A. Babcock ◽  
Felina V. Kostova ◽  
Donna M. Ferriero ◽  
Michael V. Johnston ◽  
Jan E. Brunstrom ◽  
...  

Author(s):  
Xi Guo ◽  
Tin Chiu Li ◽  
Xiaoyan Chen

Abstract Embryo implantation is an intricate process which requires competent embryo and receptive endometrium. The failure of endometrium to achieve receptivity is a recognized cause of infertility. However, due to multiplicity of events involved, the molecular mechanisms governing endometrial receptivity are still not fully understood. Traditional one-by-one approaches, including western blotting and histochemistry, are insufficient to examine the extensive changes of endometrial proteome. Although genomics and transcriptomics studies have identified several significant genes, the underlying mechanism remains to be uncovered owing to post-transcriptional and post-translational modifications. Proteomic technologies are high throughput in protein identification, and they are now intensively used to identify diagnostic and prognostic markers in the field of reproductive medicine. There is a series of studies analyzing endometrial proteomic profile, which has provided a mechanistic insight into implantation failure. These published studies mainly focused on the difference between pre-receptive and receptive stages of endometrium, as well as on the alternation of endometrial proteomics in women with reproductive failure. Here, we review recent data from proteomic analyses regarding endometrium around the time of embryo implantation and propose possible future research directions.


2021 ◽  
Vol 22 (23) ◽  
pp. 12901
Author(s):  
Xiaojing Zhang ◽  
Yin Jia ◽  
Yang Liu ◽  
Duanfen Chen ◽  
Yibo Luo ◽  
...  

Self-incompatibility affects not only the formation of seeds, but also the evolution of species diversity. A robust understanding of the molecular mechanisms of self-incompatibility is essential for breeding efforts, as well as conservation biology research. In recent years, phenotypic and multiple omics studies have revealed that self-incompatibility in Orchidaceae is mainly concentrated in the subfamily Epidendroideae, and the self-incompatibility phenotypes are diverse, even in the same genus, and hormones (auxin and ethylene), and new male and female determinants might be involved in SI response. This work provides a good foundation for future studies of the evolution and molecular mechanisms of self-incompatibility. We review recent research progress on self-incompatibility in orchids at the morphological, physiological, and molecular levels, provide a general overview of self-incompatibility in orchids, and propose future research directions.


2021 ◽  
Vol 15 (1) ◽  
pp. 69-82
Author(s):  
Mei Wang ◽  
Zheng Gong ◽  
Xinxin Zhao ◽  
Wanjun Yu ◽  
Feng Huang ◽  
...  

Gastric cancer (GC) is a common digestive malignancy with a high-ranking morbidity and mortality. Therefore, it is urgent to identify novel indicators and develop new strategies for clinical diagnosis and treatment of GC. As a type of noncoding RNA, circular RNAs (circRNAs) have received increased attention in GC during recent years. To more comprehensively understand current research progress on circRNAs in GC, in this review, we introduce basic knowledge of circRNAs, summarize abnormally expressed circRNAs and discuss their functions and regulatory molecular mechanisms in GC. Then, we review potential applications of circRNAs for GC diagnosis, prognosis and treatment. Finally, we conclude by highlighting major advancements of circRNAs in GC research, and we discuss existing challenges and possible future research directions of GC-associated circRNAs.


Author(s):  
Lidong Wang ◽  
Xiaodan Sun ◽  
Jingni He ◽  
Zhen Liu

Ubiquitination is a posttranslational modification of proteins that significantly affects protein stability and function. The specificity of substrate recognition is determined by ubiquitin E3 ligase during ubiquitination. Human Deltex (DTX) protein family, which functions as ubiquitin E3 ligases, comprises five members, namely, DTX1, DTX2, DTX3, DTX3L, and DTX4. The characteristics and functional diversity of the DTX family proteins have attracted significant attention over the last decade. DTX proteins have several physiological and pathological roles and are closely associated with cell signal transduction, growth, differentiation, and apoptosis, as well as the occurrence and development of various tumors. Although they have been extensively studied in various species, data on structural features, biological functions, and potential mechanisms of action of the DTX family proteins remain limited. In this review, recent research progress on each member of the DTX family is summarized, providing insights into future research directions and potential strategies in disease diagnosis and therapy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jia-Jian Cao ◽  
Chen-Xu Liu ◽  
Shu-Jun Shao ◽  
Jie Zhou

Autophagy is a highly conserved cellular process for the degradation and recycling of unnecessary cytoplasmic components in eukaryotes. Various studies have shown that autophagy plays a crucial role in plant growth, productivity, and survival. The extensive functions of plant autophagy have been revealed in numerous frontier studies, particularly those regarding growth adjustment, stress tolerance, the identification of related genes, and the involvement of metabolic pathways. However, elucidation of the molecular regulation of plant autophagy, particularly the upstream signaling elements, is still lagging. In this review, we summarize recent progress in research on the molecular mechanisms of autophagy regulation, including the roles of protein kinases, phytohormones, second messengers, and transcriptional and epigenetic control, as well as the relationship between autophagy and the 26S proteasome in model plants and crop species. We also discuss future research directions for the potential application of autophagy in agriculture.


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