scholarly journals Human Islet Expression Levels of Prostaglandin E2 Synthetic Enzymes, But Not Prostaglandin EP3 Receptor, Are Positively Correlated with Markers of β-Cell Function and Mass in Nondiabetic Obesity

2021 ◽  
Author(s):  
Nathan A. Truchan ◽  
Rachel J. Fenske ◽  
Harpreet K. Sandhu ◽  
Alicia M. Weeks ◽  
Chinmai Patibandla ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Cell Function ◽  
Human Islet ◽  
Β Cell ◽  
Synthetic Enzymes ◽  
Expression Levels ◽  
Β Cell Function ◽  
Ep3 Receptor

scholarly journals Lipid droplets protect human β cells from lipotoxic-induced stress and cell identity changes

2021 ◽  
Author(s):  
Xin Tong ◽  
Roland Stein
Keyword(s):  
Er Stress ◽  
Cell Function ◽  
Cell Activity ◽  
Cell Types ◽  
Human Cell Line ◽  
Human Islet ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion ◽  
Identity Changes

Free fatty acids (FFAs) are often stored in lipid droplet (LD) depots for eventual metabolic and/or synthetic use in many cell types, such a muscle, liver, and fat. In pancreatic islets, overt LD accumulation was detected in humans but not mice. LD buildup in islets was principally observed after roughly 11 years of age, increasing throughout adulthood under physiologic conditions, and also enriched in type 2 diabetes. To obtain insight into the role of LDs in human islet β cell function, the levels of a key LD scaffold protein, perilipin2 (PLIN2), were manipulated by lentiviral-mediated knock-down (KD) or over-expression (OE) in EndoCβH2-Cre cells, a human cell line with adult islet β-like properties. Glucose stimulated insulin secretion was blunted in PLIN2KD cells and improved in PLIN2OE cells. An unbiased transcriptomic analysis revealed that limiting LD formation induced effectors of endoplasmic reticulum (ER) stress that compromised the expression of critical β cell function and identity genes. These changes were essentially reversed by PLIN2OE or using the ER stress inhibitor, tauroursodeoxycholic acid. These results strongly suggest that LDs are essential for adult human islet β cell activity by preserving FFA homeostasis.<br>

scholarly journals Lipid droplets protect human β cells from lipotoxic-induced stress and cell identity changes

2021 ◽  
Author(s):  
Xin Tong ◽  
Roland W Stein
Keyword(s):  
Er Stress ◽  
Cell Function ◽  
Cell Activity ◽  
Cell Types ◽  
Human Cell Line ◽  
Human Islet ◽  
Structural Protein ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function

Free fatty acids (FFAs) are often stored in lipid droplet (LD) depots for eventual metabolic and/or synthetic use in many cell types, such a muscle, liver, and fat. In pancreatic islets, overt LD accumulation was detected in humans but not mice. LD buildup in islets was principally observed after roughly 11 years of age, increasing throughout adulthood under physiologic conditions, and also enriched in type 2 diabetes. To obtain insight into the role of LDs in human islet β cell function, the levels of a key LD structural protein, perilipin2 (PLIN2), were manipulated by lentiviral-mediated knock-down (KD) or over-expression (OE) in EndoCβH2-Cre cells, a human cell line with adult islet β-like properties. Glucose stimulated insulin secretion was blunted in PLIN2KD cells and improved in PLIN2OE cells. An unbiased transcriptomic analysis revealed that limiting LD formation induced effectors of endoplasmic reticulum (ER) stress that compromised the expression of critical β cell function and identity genes. These changes were aggravated by exogenous treatment with FFAs toxic to islet β cells, and essentially reversed by PLIN2OE or using the ER stress inhibitor, tauroursodeoxycholic acid. These results strongly suggest that LDs are essential for adult human islet β cell activity by preserving FFA homeostasis.

scholarly journals Extracellular CADM1 interactions influence insulin secretion by rat and human islet β-cells and promote clustering of syntaxin-1

2016 ◽  
Vol 310 (11) ◽  
pp. E874-E885 ◽  
Author(s):  
Charles Zhang ◽  
Thomas A. Caldwell ◽  
M. Reza Mirbolooki ◽  
Diana Duong ◽  
Eun Jee Park ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Interactions ◽  
Network Formation ◽  
Cell Function ◽  
Human Islet ◽  
Cell Contact ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function ◽  
Insulinoma Cells

Contact between β-cells is necessary for their normal function. Identification of the proteins mediating the effects of β-cell-to-β-cell contact is a necessary step toward gaining a full understanding of the determinants of β-cell function and insulin secretion. The secretory machinery of the β-cells is nearly identical to that of central nervous system (CNS) synapses, and we hypothesize that the transcellular protein interactions that drive maturation of the two secretory machineries upon contact of one cell (or neural process) with another are also highly similar. Two such transcellular interactions, important for both synaptic and β-cell function, have been identified: EphA/ephrin-A and neuroligin/neurexin. Here, we tested the role of another synaptic cleft protein, CADM1, in insulinoma cells and in rat and human islet β-cells. We found that CADM1 is a predominant CADM isoform in β-cells. In INS-1 cells and primary β-cells, CADM1 constrains insulin secretion, and its expression decreases after prolonged glucose stimulation. Using a coculture model, we found that CADM1 also influences insulin secretion in a transcellular manner. We asked whether extracellular CADM1 interactions exert their influence via the same mechanisms by which they influence neurotransmitter exocytosis. Our results suggest that, as in the CNS, CADM1 interactions drive exocytic site assembly and promote actin network formation. These results support the broader hypothesis that the effects of cell-cell contact on β-cell maturation and function are mediated by the same extracellular protein interactions that drive the formation of the presynaptic exocytic machinery. These interactions may be therapeutic targets for reversing β-cell dysfunction in diabetes.

scholarly journals Lipid droplets protect human β cells from lipotoxic-induced stress and cell identity changes

2021 ◽  
Author(s):  
Xin Tong ◽  
Roland Stein
Keyword(s):  
Er Stress ◽  
Cell Function ◽  
Cell Activity ◽  
Cell Types ◽  
Human Cell Line ◽  
Human Islet ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion ◽  
Identity Changes

Free fatty acids (FFAs) are often stored in lipid droplet (LD) depots for eventual metabolic and/or synthetic use in many cell types, such a muscle, liver, and fat. In pancreatic islets, overt LD accumulation was detected in humans but not mice. LD buildup in islets was principally observed after roughly 11 years of age, increasing throughout adulthood under physiologic conditions, and also enriched in type 2 diabetes. To obtain insight into the role of LDs in human islet β cell function, the levels of a key LD scaffold protein, perilipin2 (PLIN2), were manipulated by lentiviral-mediated knock-down (KD) or over-expression (OE) in EndoCβH2-Cre cells, a human cell line with adult islet β-like properties. Glucose stimulated insulin secretion was blunted in PLIN2KD cells and improved in PLIN2OE cells. An unbiased transcriptomic analysis revealed that limiting LD formation induced effectors of endoplasmic reticulum (ER) stress that compromised the expression of critical β cell function and identity genes. These changes were essentially reversed by PLIN2OE or using the ER stress inhibitor, tauroursodeoxycholic acid. These results strongly suggest that LDs are essential for adult human islet β cell activity by preserving FFA homeostasis.<br>

Adipokines as key players in β cell function and failure

2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo
Keyword(s):  
Metabolic Diseases ◽  
Cell Function ◽  
Whole Body ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Axis ◽  
Β Cell Function ◽  
Prevalence Of Obesity ◽  
Specific Factors ◽  
Whole Body Metabolism

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.

Effects of Ovariectomy on Insulin Resistance and β-Cell Function and Mass

2004 ◽  
Vol 9 (4) ◽  
pp. 367-373
Author(s):  
Soo-Bong Choi ◽  
Chun-Hee Park ◽  
Dong-Wha Jun ◽  
Jin-Sun Jang ◽  
Sun-Min Park
Keyword(s):  
Insulin Resistance ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function
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