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.

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.

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.

scholarly journals Oxidative Metabolism Genes Are Not Responsive to Oxidative Stress in Rodent Beta Cell Lines

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Faer Morrison ◽  
Karen Johnstone ◽  
Anna Murray ◽  
Jonathan Locke ◽  
Lorna W. Harries
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Beta Cell ◽  
Beta Cells ◽  
Oxidative Metabolism ◽  
Pancreatic Beta Cells ◽  
Ros Production ◽  
Altered Expression ◽  
Beta Cell Line

Altered expression of oxidative metabolism genes has been described in the skeletal muscle of individuals with type 2 diabetes. Pancreatic beta cells contain low levels of antioxidant enzymes and are particularly susceptible to oxidative stress. In this study, we explored the effect of hyperglycemia-induced oxidative stress on a panel of oxidative metabolism genes in a rodent beta cell line. We exposed INS-1 rodent beta cells to low (5.6 mmol/L), ambient (11 mmol/L), and high (28 mmol/L) glucose conditions for 48 hours. Increases in oxidative stress were measured using the fluorescent probe dihydrorhodamine 123. We then measured the expression levels of a panel of 90 oxidative metabolism genes by real-time PCR. Elevated reactive oxygen species (ROS) production was evident in INS-1 cells after 48 hours (P<0.05). TLDA analysis revealed a significant (P<0.05) upregulation of 16 of the 90 genes under hyperglycemic conditions, although these expression differences did not reflect differences in ROS. We conclude that although altered glycemia may influence the expression of some oxidative metabolism genes, this effect is probably not mediated by increased ROS production. The alterations to the expression of oxidative metabolism genes previously observed in human diabetic skeletal muscle do not appear to be mirrored in rodent pancreatic beta cells.

scholarly journals Stronger control of ATP/ADP by proton leak in pancreatic β-cells than skeletal muscle mitochondria

2005 ◽  
Vol 393 (1) ◽  
pp. 151-159 ◽  
Author(s):  
Charles Affourtit ◽  
Martin D. Brand
Keyword(s):  
Skeletal Muscle ◽  
Membrane Potential ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Respiratory Activity ◽  
Cell Types ◽  
Proton Leak ◽  
Control Analysis ◽  
Β Cells

Pancreatic beta cells respond to rising blood glucose concentrations by increasing their oxidative metabolism, which leads to an increased ATP/ADP ratio, closure of KATP channels, depolarization of the plasma membrane potential, influx of calcium and the eventual secretion of insulin. Such a signalling mechanism implies that the ATP/ADP ratio is flexible in beta cells (β-cells), which is in contrast with other cell types (e.g. muscle and liver) that maintain a stable ATP/ADP poise while respiring at widely varying rates. To determine whether this difference in flexibility is accounted for by mitochondrial peculiarities, we performed a top-down metabolic control analysis to quantitatively assess how ATP/ADP is controlled in mitochondria isolated from rat skeletal muscle and cultured beta cells. We show that the ATP/ADP ratio is more strongly controlled (approx. 7.5-fold) by proton leak in beta cells than in muscle. The comparatively high importance of proton leak in beta cell mitochondria (relative to phosphorylation) is evidenced furthermore by its relatively high level of control over membrane potential and overall respiratory activity. Modular-kinetic analysis of oxidative phosphorylation reveals that these control differences can be fully explained by a higher relative leak activity in beta cell mitochondria, which results in a comparatively high contribution of proton leak to the overall respiratory activity in this system.

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 Molecular Mechanism of Corticosteroid-Induced Hyperglycemia

10.51511/pr.1 ◽  
2021 ◽  
Author(s):  
Destika Ambar Sari ◽  
Galih Samodra ◽  
Ikhwan Yuda Kusuma
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Immunosuppressive Drugs ◽  
Hormone Sensitive Lipase ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Hormone Sensitive ◽  
Beta Cell Response

Corticosteroids are widely used as strong anti-inflammatory and immunosuppressive drugs to treat various diseases. However, the use of corticosteroids can cause several side effects, such as hyperglycemia. This review aims to examine the effect of corticosteroids on increasing glucose in molecular levels based on literature studies. A literature searching was carried out on the PubMed, Science Direct, and Google Scholar databases published in 2010-2020. Corticosteroids can cause an increase in blood glucose levels by several mechanisms. In the liver, glucocorticoids increase endogenous plasma glucose and stimulate gluconeogenesis. Glucocorticoids increase the production of non-esterified fatty acids which affect the signal transduction of insulin receptor substrate-1 in skeletal muscle. In adipose, glucocorticoids increase lipolysis and visceral adiposity through increased transcription and expression of protein adipose triglyceride lipase and hormone-sensitive lipase. In pancreatic beta cells, glucocorticoids directly inhibit the beta cell response to glucose through the role of protein kinase B and protein kinase C. At the molecular level, corticosteroids can cause hyperglycemia through mechanisms in the liver, skeletal muscle tissue, adipose tissue, and pancreatic beta cells.

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.

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