Tetraethylammonium modifies gap junctions between pancreatic beta-cells

1981 ◽  
Vol 240 (3) ◽  
pp. C116-C120 ◽  
Author(s):  
M. S. Sheppard ◽  
P. Meda
Keyword(s):  
Beta Cell ◽  
Gap Junctions ◽  
Beta Cells ◽  
Insulin Release ◽  
Pancreatic Beta Cells ◽  
Freeze Fracture ◽  
Potassium Conductance ◽  
Median Number ◽  
Rat Islets Of Langerhans ◽  
Gap Junctional

Gap junctions between pancreatic beta-cells were quantitatively assessed in freeze-fracture replicas of isolated rat islets of Langerhans incubated for 90 min with or without the potassium conductance blocker tetraethylammonium (TEA). The results show that TEA increases the median number of particles per beta-cell gap junction but not the frequency of gap junctions at both nonstimulating and threshold-stimulating concentrations of glucose. TEA increased the relative gap junctional area at both concentrations of glucose. TEA had no effect on insulin release at a basal concentration of glucose but potentiated that release at the threshold glucose level. Thus TEA modifies beta-cell gap junctions independently of its effect on insulin release. However, the junctional changes observed were greater when insulin release was also elevated.

Nonrandom distribution of gap junctions between pancreatic beta-cells

1980 ◽  
Vol 238 (3) ◽  
pp. C114-C119 ◽  
Author(s):  
P. Meda ◽  
J. F. Denef ◽  
A. Perrelet ◽  
L. Orci
Keyword(s):  
Insulin Secretion ◽  
Gap Junctions ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Freeze Fracture ◽  
Membrane Area ◽  
Nonrandom Distribution ◽  
Isolated Rat Islets ◽  
Rat Islets Of Langerhans ◽  
Stimulation Of

The numerical and spatial distribution of gap junctions between insulin-containing cells (beta-cells) under resting and stimulated conditions of insulin secretion were quantitatively analyzed in freeze-fracture replicas of isolated rat islets of Langerhans. The results show that the beta-cells located at the periphery of the islet have twice as many gap junctions per unit membrane area as the beta-cells situated in the islet center. In both locations, gap junctions assumed a nonrandom clustering on the beta-cell membranes. During stimulation of insulin secretion, the gap junctions were found increased between the central and between the peripheral beta-cells. The degree of their clustering was also modified. The latter change depended both on the location of the gap junctions in the islet and on the type of stimulation used (high glucose or glibenclamide).

scholarly journals Nrf2 Activation Protects Mouse Beta Cells from Glucolipotoxicity by Restoring Mitochondrial Function and Physiological Redox Balance

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Johanna Schultheis ◽  
Dirk Beckmann ◽  
Dennis Mulac ◽  
Lena Müller ◽  
Melanie Esselen ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Insulin Release ◽  
Mitochondrial Function ◽  
Pancreatic Beta Cells ◽  
Redox Balance ◽  
Nuclear Accumulation ◽  
Mitochondrial Activity ◽  
Related Factor ◽  
Nrf2 Activation

Influencing the redox balance of pancreatic beta cells could be a promising strategy for the treatment of diabetes. Nuclear factor erythroid 2p45-related factor 2 (Nrf2) is present in beta cells and regulates numerous genes involved in antioxidant defense. As reactive oxygen species (ROS) are important for beta cell signaling but induce oxidative stress when present in excess, this study elucidates the influence of Nrf2-activating compounds on different kinds of ROS and correlates changes in redox balance to effects on mitochondrial function, insulin release, and cell viability. Acute glucose stimulation (15 mmol/L) of murine islet cells of C57Bl/6N mice affects ROS and redox status of the cells differently. Those ROS monitored by dihydroethidium, which detects superoxide radical anions, decrease. By contrast, oxidant status, monitored by dichlorodihydrofluorescein, as well as intracellular H2O2, increases. Glucolipotoxicity completely prevents these fast, glucose-mediated alterations and inhibits glucose-induced NAD(P)H production, mitochondrial hyperpolarization, and ATP synthesis. Oltipraz (10 μmol/L) or dimethyl fumarate (DMF, 50 μmol/L) leads to nuclear accumulation of Nrf2, restores mitochondrial activity and glucose-dependent ROS turnover, and antagonizes glucolipotoxicity-induced inhibition of insulin release and apoptosis. Importantly, these beneficial effects only occur when beta cells are challenged and damaged by high lipid and carbohydrate supply. At physiological conditions, insulin release is markedly reduced in response to both Nrf2 activators. This is not associated with severe impairment of glucose-induced mitochondrial hyperpolarization or a rise in apoptosis but coincides with altered ROS handling. In conclusion, Nrf2 activators protect beta cells against glucolipotoxicity by preserving mitochondrial function and redox balance. As our data show that this maintains glucose-stimulated insulin secretion, targeting Nrf2 might be suited to ameliorate progression of type 2 diabetes mellitus. By contrast, nonstressed beta cells do not benefit from Nrf2 activation, thus underlining the importance of physiological shifts in ROS homeostasis for the regulation of beta cell function.

I scream, you scream, we all scream for irisin

2017 ◽  
Vol 9 (402) ◽  
pp. eaao2263 ◽  
Author(s):  
Ashley Shoemaker
Keyword(s):  
Skeletal Muscle ◽  
Beta Cell ◽  
Cell Survival ◽  
Beta Cells ◽  
Insulin Release ◽  
Pancreatic Beta Cells

Skeletal muscle may communicate with pancreatic beta cells through irisin, a muscle-derived hormone that promotes beta cell survival and insulin release.

scholarly journals Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 104
Author(s):  
Elisa Fernández-Millán ◽  
Carlos Guillén
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Cell Biology ◽  
Pancreatic Beta Cells ◽  
Metabolic Diseases ◽  
Cell Function ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Short Chain Fatty Acids

Type 2 diabetes (T2D) results from impaired beta-cell function and insufficient beta-cell mass compensation in the setting of insulin resistance. Current therapeutic strategies focus their efforts on promoting the maintenance of functional beta-cell mass to ensure appropriate glycemic control. Thus, understanding how beta-cells communicate with metabolic and non-metabolic tissues provides a novel area for investigation and implicates the importance of inter-organ communication in the pathology of metabolic diseases such as T2D. In this review, we provide an overview of secreted factors from diverse organs and tissues that have been shown to impact beta-cell biology. Specifically, we discuss experimental and clinical evidence in support for a role of gut to beta-cell crosstalk, paying particular attention to bacteria-derived factors including short-chain fatty acids, lipopolysaccharide, and factors contained within extracellular vesicles that influence the function and/or the survival of beta cells under normal or diabetogenic conditions.

scholarly journals Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0241349
Author(s):  
Sajid Ali Rajput ◽  
Munazza Raza Mirza ◽  
M. Iqbal Choudhary
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cells ◽  
Proinflammatory Cytokines ◽  
Cell Apoptosis ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Beta Cell Apoptosis ◽  
Atp Levels ◽  
Induced Apoptosis

Beta cell apoptosis induced by proinflammatory cytokines is one of the hallmarks of diabetes. Small molecules which can inhibit the cytokine-induced apoptosis could lead to new drug candidates that can be used in combination with existing therapeutic interventions against diabetes. The current study evaluated several effects of bergenin, an isocoumarin derivative, in beta cells in the presence of cytokines. These included (i) increase in beta cell viability (by measuring cellular ATP levels) (ii) suppression of beta cell apoptosis (by measuring caspase activity), (iii) improvement in beta cell function (by measuring glucose-stimulated insulin secretion), and (iv) improvement of beta cells mitochondrial physiological functions. The experiments were carried out using rat beta INS-1E cell line in the presence or absence of bergenin and a cocktail of proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon- gamma) for 48 hr. Bergenin significantly inhibited beta cell apoptosis, as inferred from the reduction in the caspase-3 activity (IC50 = 7.29 ± 2.45 μM), and concurrently increased cellular ATP Levels (EC50 = 1.97 ± 0.47 μM). Bergenin also significantly enhanced insulin secretion (EC50 = 6.73 ± 2.15 μM) in INS-1E cells, presumably because of the decreased nitric oxide production (IC50 = 6.82 ± 2.83 μM). Bergenin restored mitochondrial membrane potential (EC50 = 2.27 ± 0.83 μM), decreased ROS production (IC50 = 14.63 ± 3.18 μM), and improved mitochondrial dehydrogenase activity (EC50 = 1.39 ± 0.62 μM). This study shows for the first time that bergenin protected beta cells from cytokine-induced apoptosis and restored insulin secretory function by virtue of its anti-inflammatory, antioxidant and anti-apoptotic properties. To sum up, the above mentioned data highlight bergenin as a promising anti-apoptotic agent in the context of diabetes.

scholarly journals Glucose controls co-translation of structurally related mRNAs via the mTOR and eIF2 pathways in human pancreatic beta cells

2021 ◽  
Author(s):  
Manuel Bulfoni ◽  
Costas Bouyioukos ◽  
Albatoul Zakaria ◽  
Fabienne Nigon ◽  
Roberta Rapone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Gene Expression Regulation ◽  
Human Cells ◽  
Rodent Models ◽  
Polysome Profiling ◽  
Acute Increase

ABSTRACTPancreatic beta cell response to glucose is critical for the maintenance of normoglycemia. A strong transcriptional response was classically described in rodent models but, interestingly, not in human cells. In this study, we exposed human pancreatic beta cells to an increased concentration of glucose and analysed at a global level the mRNAs steady state levels and their translationalability. Polysome profiling analysis showed an early acute increase in protein synthesis and a specific translation regulation of more than 400 mRNAs, independently of their transcriptional regulation. We clustered the co-regulated mRNAs according to their behaviour in translation in response to glucose and discovered common structural and sequence mRNA features. Among them mTOR- and eIF2-sensitive elements have a predominant role to increase mostly the translation of mRNAs encoding for proteins of the translational machinery. Furthermore, we show that mTOR and eIF2α pathways are independently regulated in response to glucose, participating to a translational reshaping to adapt beta cell metabolism. The early acute increase in the translation machinery components prepare the beta cell for further protein demand due to glucose-mediated metabolism changes.AUTHOR SUMMARYAdaptation and response to glucose of pancreatic beta cells is critical for the maintenance of normoglycemia. Its deregulation is associated to Diabetic Mellitus (DM), a significant public health concern worldwide with an increased incidence of morbidity and mortality. Despite extensive research in rodent models, gene expression regulation in response to glucose remains largely unexplored in human cells. In our work, we have tackled this question by exposing human EndoC-BH1 cells to high glucose concentration. Using polysome profiling, the gold standard technique to analyse cellular translation activity, we observed a global protein synthesis increase, independent from transcription activity. Among the specific differentially translated mRNAs, we found transcripts coding for ribosomal proteins, allowing the cell machinery to be engaged in a metabolic response to glucose. Therefore, the regulation in response to glucose occurs mainly at the translational level in human cells, and not at the transcriptional level as described in the classically used rodent models.Furthermore, by comparing the features of the differentially translated mRNAs, and classifying them according to their translational response, we show that the early response to glucose occurs through the coupling of mRNA structure and sequence features impacting translation and regulation of specific signalling pathways. Collectively, our results support a new paradigm of gene expression regulation on the translation level in human beta cells.

2089268 Ultrasound Stimulation of Insulin Release From Pancreatic Beta Cells

2015 ◽  
Vol 41 (4) ◽  
pp. S65 ◽  
Author(s):  
Ivan Mauricio Suarez Castellanos ◽  
Aleksandar Jeremic ◽  
Vesna Zderic
Keyword(s):  
Beta Cells ◽  
Insulin Release ◽  
Pancreatic Beta Cells ◽  
Ultrasound Stimulation ◽  
Stimulation Of

scholarly journals Update on the Protective Molecular Pathways Improving Pancreatic Beta-Cell Dysfunction

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
François Mach ◽  
Franco Dallegri ◽  
Giorgio Luciano Viviani ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Dysfunction ◽  
Molecular Pathways ◽  
Cell Dysfunction

The primary function of pancreatic beta-cells is to produce and release insulin in response to increment in extracellular glucose concentrations, thus maintaining glucose homeostasis. Deficient beta-cell function can have profound metabolic consequences, leading to the development of hyperglycemia and, ultimately, diabetes mellitus. Therefore, strategies targeting the maintenance of the normal function and protecting pancreatic beta-cells from injury or death might be crucial in the treatment of diabetes. This narrative review will update evidence from the recently identified molecular regulators preserving beta-cell mass and function recovery in order to suggest potential therapeutic targets against diabetes. This review will also highlight the relevance for novel molecular pathways potentially improving beta-cell dysfunction.

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