scholarly journals A pipeline for multidimensional confocal analysis of mitochondrial morphology, function and dynamics in pancreatic β-cells

2019 ◽  
Author(s):  
Ahsen Chaudhry ◽  
Rocky Shi ◽  
Dan S. Luciani
Keyword(s):  
Metabolic Diseases ◽  
Super Resolution ◽  
Cell Types ◽  
Mitochondrial Morphology ◽  
State Function ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Health And Disease ◽  
Mitochondrial Networks ◽  
Functional Analyses

ABSTRACTLive-cell imaging of mitochondrial function and dynamics can provide vital insights into both physiology and pathophysiology, including of metabolic diseases like type 2 diabetes. However, without super-resolution microscopy and commercial analysis software it is challenging to accurately extract features from dense multi-layered mitochondrial networks, such as those in insulin-secreting pancreatic β-cells. Motivated by this, we developed a comprehensive pipeline, and associated ImageJ plugin, that enables 2D/3D quantification of mitochondrial network morphology and dynamics in mouse β-cells, and by extension other similarly challenging cell-types. The approach is based on standard confocal microscopy and shareware, making it widely accessible. The pipeline was validated using mitochondrial photo-labelling and unsupervised cluster analysis, and is capable of morphological and functional analyses on a per-organelle basis, including in 4D (xyzt). Overall, this tool offers a powerful framework for multiplexed analysis of mitochondrial state/function, and provides a valuable resource to accelerate mitochondrial research in health and disease.

scholarly journals A pipeline for multidimensional confocal analysis of mitochondrial morphology, function, and dynamics in pancreatic β-cells

2020 ◽  
Vol 318 (2) ◽  
pp. E87-E101 ◽  
Author(s):  
Ahsen Chaudhry ◽  
Rocky Shi ◽  
Dan S. Luciani
Keyword(s):  
Metabolic Diseases ◽  
Super Resolution ◽  
Cell Types ◽  
Mitochondrial Morphology ◽  
State Function ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Health And Disease ◽  
Mitochondrial Networks ◽  
Functional Analyses

Live-cell imaging of mitochondrial function and dynamics can provide vital insights into both physiology and pathophysiology, including of metabolic diseases like type 2 diabetes. However, without super-resolution microscopy and commercial analysis software, it is challenging to accurately extract features from dense multilayered mitochondrial networks, such as those in insulin-secreting pancreatic β-cells. Motivated by this, we developed a comprehensive pipeline and associated ImageJ plugin that enables 2D/3D quantification of mitochondrial network morphology and dynamics in mouse β-cells and by extension other similarly challenging cell types. The approach is based on standard confocal microscopy and shareware, making it widely accessible. The pipeline was validated using mitochondrial photolabeling and unsupervised cluster analysis and is capable of morphological and functional analyses on a per-organelle basis, including in 4D ( xyzt). Overall, this tool offers a powerful framework for multiplexed analysis of mitochondrial state/function and provides a valuable resource to accelerate mitochondrial research in health and disease.

scholarly journals Do skeletal muscle-secreted factors influence the function of pancreatic β-cells?

2018 ◽  
Vol 314 (4) ◽  
pp. E297-E307 ◽  
Author(s):  
Jonathan P. Barlow ◽  
Thomas P. Solomon
Keyword(s):  
Skeletal Muscle ◽  
Cross Talk ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Ongoing Research ◽  
Secreted Factors ◽  
Health And Disease ◽  
Endocrine Signaling

Skeletal muscle is an endocrine organ that secretes a variety of compounds including proteins (myokines), metabolites, microRNAs (miRNAs), and exosomes, many of which are regulated by exercise and play important roles in endocrine signaling. Interorgan communication via muscle-secreted factors therefore provides a novel area for investigation and implicates the importance of skeletal muscle in the pathophysiology of metabolic diseases such as type 2 diabetes (T2D). Given that underlying molecular mechanisms of T2D are subject of ongoing research, in light of new evidence it is probable that interorgan cross-talk between skeletal muscle and pancreatic β-cells plays an important part. To date, the number of studies published in this field provide the basis of this review. Specifically, we discuss current experimental evidence in support for a role of skeletal muscle to β-cell cross-talk, paying particular attention to muscle-secreted factors including myokines, metabolites, miRNAs, and factors contained within exosomes that influence the function and/or the survival of β-cells in health and disease. In reviewing this evidence, we provide an update on the list of known muscle-secreted factors that have potential to influence the function and/or survival of β-cells under normal and diabetic conditions. We also report limitations of current cross-talk methods and discuss future directions in this growing field.

Autophagy in health and disease. 4. The role of pancreatic β-cell autophagy in health and diabetes

2010 ◽  
Vol 299 (1) ◽  
pp. C1-C6 ◽  
Author(s):  
Yoshio Fujitani ◽  
Takashi Ueno ◽  
Hirotaka Watada
Keyword(s):  
Cell Mass ◽  
Normal Function ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Ubiquitinated Proteins ◽  
Evolutionarily Conserved ◽  
Health And Disease ◽  
Cellular Stresses

Autophagy is an evolutionarily conserved machinery for degradation and recycling of various cytoplasmic components such as long-lived proteins and organelles. In pancreatic β-cells, as in most other cells, autophagy is also important for the low basal turnover of ubiquitinated proteins and damaged organelles under normal conditions. Insulin resistance results in upregulation of autophagic activity in β-cells. Induced autophagy in β-cells plays a pivotal role in the adaptive expansion of β-cell mass. Nevertheless, it is not clear whether autophagy is protective or detrimental in response to cellular stresses in β-cells. In this review, we describe the crucial roles of autophagy in normal function of β-cells and discuss how dysfunction of the autophagic machinery could lead to the development of diabetes mellitus.

Rat liver endothelial cell glutamine transporter and glutaminase expression contrast with parenchymal cells

1999 ◽  
Vol 276 (3) ◽  
pp. G743-G750 ◽  
Author(s):  
Rüdiger Lohmann ◽  
Wiley W. Souba ◽  
Barrie P. Bode
Keyword(s):  
Endothelial Cells ◽  
Amino Acid ◽  
Cell Types ◽  
Male Rats ◽  
Specific Cell ◽  
Liver Endothelial Cell ◽  
Glutamine Transporter ◽  
Health And Disease ◽  
Parenchymal Cells ◽  
Functional Analyses

Despite the central role of the liver in glutamine homeostasis in health and disease, little is known about the mechanism by which this amino acid is transported into sinusoidal endothelial cells, the second most abundant hepatic cell type. To address this issue, the transport ofl-glutamine was functionally characterized in hepatic endothelial cells isolated from male rats. On the basis of functional analyses, including kinetics, cation substitution, and amino acid inhibition, it was determined that a Na+-dependent carrier distinct from system N in parenchymal cells, with properties of system ASC or B0, mediated the majority of glutamine transport in hepatic endothelial cells. These results were supported by Northern blot analyses that showed expression of the ATB0 transporter gene in endothelial but not parenchymal cells. Concurrently, it was determined that, whereas both cell types express glutamine synthetase, hepatic endothelial cells express the kidney-type glutaminase isozyme in contrast to the liver-type isozyme in parenchymal cells. This represents the first report of ATB0 and kidney-type glutaminase isozyme expression in the liver, observations that have implications for roles of specific cell types in hepatic glutamine homeostasis in health and disease.

scholarly journals Glucocorticoid receptor action in metabolic and neuronal function

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1208 ◽  
Author(s):  
Michael J. Garabedian ◽  
Charles A. Harris ◽  
Freddy Jeanneteau
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Health And Disease ◽  
And Behavior ◽  
External Signals ◽  
The Brain

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.

scholarly journals Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Laura Marroqui ◽  
Miguel Lopes ◽  
Reinaldo S dos Santos ◽  
Fabio A Grieco ◽  
Merja Roivainen ◽  
...  
Keyword(s):  
Gene Networks ◽  
Viral Infections ◽  
Islet Cells ◽  
Global Gene Expression ◽  
Cell Types ◽  
Autoimmune Response ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Antiviral Responses ◽  
Different Cell Types

Type 1 diabetes (T1D) is an autoimmune disease caused by loss of pancreatic β cells via apoptosis while neighboring α cells are preserved. Viral infections by coxsackieviruses (CVB) may contribute to trigger autoimmunity in T1D. Cellular permissiveness to viral infection is modulated by innate antiviral responses, which vary among different cell types. We presently describe that global gene expression is similar in cytokine-treated and virus-infected human islet cells, with up-regulation of gene networks involved in cell autonomous immune responses. Comparison between the responses of rat pancreatic α and β cells to infection by CVB5 and 4 indicate that α cells trigger a more efficient antiviral response than β cells, including higher basal and induced expression of STAT1-regulated genes, and are thus better able to clear viral infections than β cells. These differences may explain why pancreatic β cells, but not α cells, are targeted by an autoimmune response during T1D.

scholarly journals Osteocalcin as a potential risk biomarker for cardiovascular and metabolic diseases

2016 ◽  
Vol 54 (10) ◽  
Author(s):  
Paolo Magni ◽  
Chiara Macchi ◽  
Cesare R. Sirtori ◽  
Massimiliano Marco Corsi Romanelli
Keyword(s):  
Carotid Atherosclerosis ◽  
Metabolic Diseases ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Current Evidence ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Actual Relationship ◽  
Open Issues

AbstractClear evidence supports a role for circulating and locally-produced osteocalcin (OC) in the pathophysiology of cardiovascular (CV) lesions and CV risk, also in combination with metabolic changes, including type 2 diabetes mellitus (T2DM). Reduced plasma OC levels are associated with greater incidence of pathological CV changes, like arterial and valvular calcification, coronary and carotid atherosclerosis and increased carotid intima-media thickness. The actual relationship between OC levels and incidence of major CV events is, however, still unclear. Moreover, reduced circulating OC levels have been mostly associated with insulin resistance, metabolic syndrome or T2DM, indicating relevant OC actions on pancreatic β-cells and insulin secretion and activity. Based on these observations, this review article will attempt to summarize the current evidence on the potential usefulness of circulating OC as a biomarker for CV and metabolic risk, also evaluating the currently open issues in this area of research.

scholarly journals Targeted delivery of antisense oligonucleotides to pancreatic β-cells

2018 ◽  
Vol 4 (10) ◽  
pp. eaat3386 ◽  
Author(s):  
C. Ämmälä ◽  
W. J. Drury ◽  
L. Knerr ◽  
I. Ahlstedt ◽  
P. Stillemark-Billton ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Target Genes ◽  
Cell Types ◽  
Cell Type Specificity ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucagon Like Peptide 1 ◽  
Novel Therapeutic

Antisense oligonucleotide (ASO) silencing of the expression of disease-associated genes is an attractive novel therapeutic approach, but treatments are limited by the ability to deliver ASOs to cells and tissues. Following systemic administration, ASOs preferentially accumulate in liver and kidney. Among the cell types refractory to ASO uptake is the pancreatic insulin-secreting β-cell. Here, we show that conjugation of ASOs to a ligand of the glucagon-like peptide-1 receptor (GLP1R) can productively deliver ASO cargo to pancreatic β-cells both in vitro and in vivo. Ligand-conjugated ASOs silenced target genes in pancreatic islets at doses that did not affect target gene expression in liver or other tissues, indicating enhanced tissue and cell type specificity. This finding has potential to broaden the use of ASO technology, opening up novel therapeutic opportunities, and presents an innovative approach for targeted delivery of ASOs to additional cell types.

scholarly journals Calcium Signaling in ß-cell Physiology and Pathology: A Revisit

2019 ◽  
Vol 20 (24) ◽  
pp. 6110 ◽  
Author(s):  
Christiane Klec ◽  
Gabriela Ziomek ◽  
Martin Pichler ◽  
Roland Malli ◽  
Wolfgang F. Graier
Keyword(s):  
Calcium Signaling ◽  
Adult Population ◽  
Cell Physiology ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Health And Disease

Pancreatic beta (β) cell dysfunction results in compromised insulin release and, thus, failed regulation of blood glucose levels. This forms the backbone of the development of diabetes mellitus (DM), a disease that affects a significant portion of the global adult population. Physiological calcium (Ca2+) signaling has been found to be vital for the proper insulin-releasing function of β-cells. Calcium dysregulation events can have a dramatic effect on the proper functioning of the pancreatic β-cells. The current review discusses the role of calcium signaling in health and disease in pancreatic β-cells and provides an in-depth look into the potential role of alterations in β-cell Ca2+ homeostasis and signaling in the development of diabetes and highlights recent work that introduced the current theories on the connection between calcium and the onset of diabetes.

Regulatory effects of N-3 PUFAs on pancreatic β-cells and insulin-sensitive tissues

2021 ◽  
Vol 22 ◽  
Author(s):  
Wen Liu ◽  
Qing Zheng ◽  
Min Zhu ◽  
Xiaohong Liu ◽  
Jingping Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Secretion ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Nonalcoholic Fatty Liver ◽  
Wide Range ◽  
Regulatory Effects

: The N-3 polyunsaturated fatty acids (PUFAs) have a wide range of health benefits, including anti-inflammatory effects, improvements in lipids metabolism and promoting insulin secretion, as well as reduction of cancer risk. Numerous studies support that N-3 PUFAs have the potentials to improve many metabolic diseases, such as diabetes, nonalcoholic fatty liver disease and obesity, which are attributable to N-3 PUFAs mediated enhancement of insulin secretion by pancreatic β-cells and improvements in insulin sensitivity and metabolic disorders in peripheral insulin-sensitive tissues such as liver, muscles, and adipose tissue. In this review, we summarized the up-to-date clinical and basic studies on the regulatory effects and molecular mechanisms of N-3 PUFAs mediated benefits on pancreatic β-cells, adipose tissue, liver, and muscles in the context of glucose and/or lipid metabolic disorders. We also discussed the potential factors involved in the inconsistent results from different clinical researches of N-3 PUFAs.

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