scholarly journals Role of endoplasmic reticulum stress and thrombosis in type 2 diabetes‐induced vascular dysfunction

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Karima Ait Aissa ◽  
Modar Kassan ◽  
Mohamed Trebak ◽  
Souad Belmadani ◽  
Khalid Matrougui
Keyword(s):  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Vascular Dysfunction

scholarly journals Increased monocyte-derived reactive oxygen species in type 2 diabetes: role of endoplasmic reticulum stress

2017 ◽  
Vol 102 (2) ◽  
pp. 139-153 ◽  
Author(s):  
Robert M. Restaino ◽  
Shekhar H. Deo ◽  
Alan R. Parrish ◽  
Paul J. Fadel ◽  
Jaume Padilla
Keyword(s):  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Bottom-up proteomics analysis of the secretome of murine islets of Langerhans in elevated glucose levels

The Analyst ◽  
2017 ◽  
Vol 142 (2) ◽  
pp. 284-291 ◽  
Author(s):  
Andrew Schmudlach ◽  
Jeremy Felton ◽  
Robert T. Kennedy ◽  
Norman J. Dovichi
Keyword(s):  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Oxidative Damage ◽  
Islets Of Langerhans ◽  
High Glucose ◽  
Proteomics Analysis ◽  
Glucose Levels ◽  
Elevated Glucose

Glucotoxicity is a causative agent of type-2 diabetes, where high glucose levels damage the islets of Langerhans resulting in oxidative damage and endoplasmic reticulum stress.

scholarly journals Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 395-409 ◽  
Author(s):  
Masaya Oshima ◽  
Séverine Pechberty ◽  
Lara Bellini ◽  
Sven O. Göpel ◽  
Mélanie Campana ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Identity ◽  
Human Beta Cells ◽  
Human Beta Cell ◽  
Stearoyl Coa Desaturase

Abstract Aims/hypothesis During the onset of type 2 diabetes, excessive dietary intake of saturated NEFA and fructose lead to impaired insulin production and secretion by insulin-producing pancreatic beta cells. The majority of data on the deleterious effects of lipids on functional beta cell mass were obtained either in vivo in rodent models or in vitro using rodent islets and beta cell lines. Translating data from rodent to human beta cells remains challenging. Here, we used the human beta cell line EndoC-βH1 and analysed its sensitivity to a lipotoxic and glucolipotoxic (high palmitate with or without high glucose) insult, as a way to model human beta cells in a type 2 diabetes environment. Methods EndoC-βH1 cells were exposed to palmitate after knockdown of genes related to saturated NEFA metabolism. We analysed whether and how palmitate induces apoptosis, stress and inflammation and modulates beta cell identity. Results EndoC-βH1 cells were insensitive to the deleterious effects of saturated NEFA (palmitate and stearate) unless stearoyl CoA desaturase (SCD) was silenced. SCD was abundantly expressed in EndoC-βH1 cells, as well as in human islets and human induced pluripotent stem cell-derived beta cells. SCD silencing induced markers of inflammation and endoplasmic reticulum stress and also IAPP mRNA. Treatment with the SCD products oleate or palmitoleate reversed inflammation and endoplasmic reticulum stress. Upon SCD knockdown, palmitate induced expression of dedifferentiation markers such as SOX9, MYC and HES1. Interestingly, SCD knockdown by itself disrupted beta cell identity with a decrease in mature beta cell markers INS, MAFA and SLC30A8 and decreased insulin content and glucose-stimulated insulin secretion. Conclusions/interpretation The present study delineates an important role for SCD in the protection against lipotoxicity and in the maintenance of human beta cell identity. Data availability Microarray data and all experimental details that support the findings of this study have been deposited in in the GEO database with the GSE130208 accession code.

scholarly journals Vascular Disease in Diabetic Women: Why Do They Miss the Female Protection?

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ana Paula Villela Dantas ◽  
Zuleica Bruno Fortes ◽  
Maria Helena Catelli de Carvalho
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Vascular Disease ◽  
Vascular Dysfunction ◽  
Protective Effects ◽  
Vascular Protection

Gender plays a pivotal role in the onset as well as in the progression of the cardiovascular disease with a higher morbidity and mortality being detected in men with respect to women. Type 2 Diabetes Mellitus (T2DM) may reduce gender-related differences in the prevalence of cardiovascular disease by fading the vascular protective effects afforded by estrogen in females. This article will discuss the role of sex and sex hormones on the incidence and mechanisms involved in vascular dysfunction associated to T2DM, which might explain why women with T2DM lack the vascular protection.

scholarly journals Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?

2019 ◽  
Vol 20 (15) ◽  
pp. 3775 ◽  
Author(s):  
Cesar A. Meza ◽  
Justin D. La Favor ◽  
Do-Houn Kim ◽  
Robert C. Hickner
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Enzymatic Production

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

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