scholarly journals High glucose triggers multiple cellular stress signaling in pancreatic β-cells and potentiate proinflammation and β-cell dysfunction

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Srividhya Raghavan ◽  
Viswanathan Mohan ◽  
Muthuswamy Balasubramanyam
Keyword(s):  
High Glucose ◽  
Cellular Stress ◽  
Stress Signaling ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Cell Dysfunction

scholarly journals FMK, an Inhibitor of p90RSK, Inhibits High Glucose-Induced TXNIP Expression via Regulation of ChREBP in Pancreatic β Cells

2019 ◽  
Vol 20 (18) ◽  
pp. 4424
Author(s):  
Jung-Hwa Han ◽  
Suji Kim ◽  
Suji Kim ◽  
Heejung Lee ◽  
So-Young Park ◽  
...  
Keyword(s):  
High Glucose ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Nuclear Translocation ◽  
Ros Generation ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Interacting Protein ◽  
Cell Dysfunction

Hyperglycemia is the major characteristic of diabetes mellitus, and a chronically high glucose (HG) level causes β-cell glucolipotoxicity, which is characterized by lipid accumulation, impaired β-cell function, and apoptosis. TXNIP (Thioredoxin-interacting protein) is a key mediator of diabetic β-cell apoptosis and dysfunction in diabetes, and thus, its regulation represents a therapeutic target. Recent studies have reported that p90RSK is implicated in the pathogenesis of diabetic cardiomyopathy and nephropathy. In this study, we used FMK (a p90RSK inhibitor) to determine whether inhibition of p90RSK protects β-cells from chronic HG-induced TXNIP expression and to investigate the molecular mechanisms underlying the effect of FMK on its expression. In INS-1 pancreatic β-cells, HG-induced β-cell dysfunction, apoptosis, and ROS generation were significantly diminished by FMK. In contrast BI-D1870 (another p90RSK inhibitor) did not attenuate HG-induced TXNIP promoter activity or TXNIP expression. In addition, HG-induced nuclear translocation of ChREBP and its transcriptional target molecules were found to be regulated by FMK. These results demonstrate that HG-induced pancreatic β-cell dysfunction resulting in HG conditions is associated with TXNIP expression, and that FMK is responsible for HG-stimulated TXNIP gene expression by inactivating the regulation of ChREBP in pancreatic β-cells. Taken together, these findings suggest FMK may protect against HG-induced β-cell dysfunction and TXNIP expression by ChREBP regulation in pancreatic β-cells, and that FMK is a potential therapeutic reagent for the drug development of diabetes and its complications.

Chlorogenic acid and β-glucan from highland barley grain ameliorate β cell dysfunction via inhibiting apoptosis and improving cell proliferation

2021 ◽  
Author(s):  
Zehua Liu ◽  
Bo Li
Keyword(s):  
Cell Proliferation ◽  
Chlorogenic Acid ◽  
Barley Grain ◽  
Whole Grain ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Active Compounds ◽  
Cell Dysfunction ◽  
Highland Barley

Recent studies support the view that highland barley as whole grain diet showed anti-hyperglycemic effects, while little information is available about the active compounds that could ameliorate pancreatic β cells...

scholarly journals Neuroligin-2-derived peptide-covered polyamidoamine-based (PAMAM) dendrimers enhance pancreatic β-cells' proliferation and functions

MedChemComm ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 280-293
Author(s):  
Anna Munder ◽  
Yoni Moskovitz ◽  
Aviv Meir ◽  
Shirin Kahremany ◽  
Laura Levy ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cellular Stress ◽  
Pamam Dendrimers ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Cell Functions ◽  
Functional Maturation ◽  
Glucose Stimulated Insulin Secretion

The nanoscale composite improved β-cell functions in terms of rate of proliferation, glucose-stimulated insulin secretion, resistance to cellular stress and functional maturation.

Sustained exposure of toxically damaged mouse pancreatic islets to high glucose does not increase β-cell dysfunction

1989 ◽  
Vol 123 (1) ◽  
pp. 47-51 ◽  
Author(s):  
D. L. Eizirik ◽  
S. Sandler
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
High Glucose ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Stimulation ◽  
Cell Dysfunction ◽  
Mouse Pancreatic Islets ◽  
Insulin Secretory Response

ABSTRACT The aim of this study was to clarify whether prolonged in-vitro exposure of either normal or damaged β cells to a high glucose environment can be toxic to these cells. For this purpose NMRI mice were injected intravenously with a diabetogenic dose of streptozotocin (SZ; 160 mg/kg) or vehicle alone (controls). Their islets were isolated 15 min after the injection and subsequently maintained in culture for 21 days in the presence of 11·1 or 28 mmol glucose/l. After this period, during acute glucose stimulation, the control islets showed a marked increase in their insulin release in response to a high glucose stimulus. In the SZ-exposed islets there was a decrease in DNA and insulin contents, and a deficient insulin secretory response to glucose. However, in the SZ-damaged islets as well as in the control islets, culture with 28 mmol glucose/l compared with 11·1 mmol glucose/l did not impair islet retrieval after culture, islet DNA content or glucose-induced insulin release. Thus, the degree of damage was similar in the SZ-treated islets cultured at the two concentrations of glucose. These results suggest that glucose is not toxic to normal or damaged mouse pancreatic islets over a prolonged period in tissue culture. Journal of Endocrinology (1989) 123, 47–51

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.

Cyanidin-3-rutinoside protects INS-1 pancreatic β cells against high glucose-induced glucotoxicity by apoptosis

2018 ◽  
Vol 73 (7-8) ◽  
pp. 281-289 ◽  
Author(s):  
Kung-Ha Choi ◽  
Mi Hwa Park ◽  
Hyun Ah Lee ◽  
Ji-Sook Han
Keyword(s):  
Cell Death ◽  
High Glucose ◽  
Cell Damage ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Induced Apoptosis

Abstract Exposure to high levels of glucose may cause glucotoxicity, leading to pancreatic β cell dysfunction, including cell apoptosis and impaired glucose-stimulated insulin secretion. The aim of this study was to explore the effect of cyanidin-3-rutinoside (C3R), a derivative of anthocyanin, on glucotoxicity-induced apoptosis in INS-1 pancreatic β cells. Glucose (30 mM) treatment induced INS-1 pancreatic β cell death, but glucotoxicity and apoptosis significantly decreased in cells treated with 50 μM C3R compared to that observed in 30 mM glucose-treated cells. Furthermore, hyperglycemia increased intracellular reactive oxygen species (ROS), lipid peroxidation, and nitric oxide (NO) levels, while C3R treatment reduced these in a dose-dependent manner. C3R also increased the activity of antioxidant enzymes, markedly reduced the expression of pro-apoptotic proteins (such as Bax, cytochrome c, caspase 9 and caspase 3), and increased the expression of the anti-apoptotic protein, Bcl-2, in hyperglycemia-exposed cells. Finally, cell death was examined using annexin V/propidium iodide staining, which revealed that C3R significantly reduced high glucose-induced apoptosis. In conclusion, C3R may have therapeutic effects against hyperglycemia-induced β cell damage in diabetes.

Angiotensin II exerts glucose-dependent effects on Kv currents in mouse pancreatic β-cells via angiotensin II type 2 receptors

2010 ◽  
Vol 298 (2) ◽  
pp. C313-C323 ◽  
Author(s):  
Kwan Yi Chu ◽  
Qianni Cheng ◽  
Chen Chen ◽  
Lai Shan Au ◽  
Sai Wang Seto ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
High Glucose ◽  
Prolonged Exposure ◽  
Current Amplitude ◽  
Ang Ii ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
External Application

Hyperglycemia-associated glucotoxicity induces β-cell apoptosis but the underlying mechanisms are unknown. Interestingly, prolonged exposure to high glucose upregulates the expression and function of the renin-angiotensin system (RAS). We hypothesize that the voltage-gated outward potassium (Kv) current, which governs β-cell membrane potential and insulin secretion, has a role in glucotoxicity. In this study, we investigated the effects of prolonged exposure to high glucose on mouse pancreatic β-cells and concurrent effects on the RAS by examining changes in expression of angiotensin II (ANG II) receptors and changes in the expression and activity of Kv channels. β-Cells were incubated in high glucose medium for 1–7 days and then were examined with electrophysiological and molecular biology techniques. Prolonged exposure to high glucose produced a marked increase in β-cell primary Kv channel subunit, Kv2.1, expression and Kv current amplitude. Enhanced expression of ANG II type 1 receptor (AT1R) was also observed under high glucose conditions, whereas blockade of AT1R by losartan did not alter Kv channel expression. External application of ANG II reduced Kv current amplitude under normal, but not high, glucose conditions. The effect of ANG II on Kv channel gating was abolished by ANG II type 2 receptor (AT2R) antagonism. These data suggest that hyperglycemia alters β-cell function through modification of the Kv channel which may be associated with the RAS.

scholarly journals SIRT6 protects against palmitate-induced pancreatic β-cell dysfunction and apoptosis

2016 ◽  
Vol 231 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Xiwen Xiong ◽  
Xupeng Sun ◽  
Qingzhi Wang ◽  
Xinlai Qian ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Mrna Levels ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Glucose Stimulation ◽  
Cell Dysfunction ◽  
High Concentrations ◽  
Glucose Stimulated Insulin Secretion

Chronic exposure of pancreatic β-cells to abnormally elevated levels of free fatty acids can lead to β-cell dysfunction and even apoptosis, contributing to type 2 diabetes pathogenesis. In pancreatic β-cells, sirtuin 6 (SIRT6) has been shown to regulate insulin secretion in response to glucose stimulation. However, the roles played by SIRT6 in β-cells in response to lipotoxicity remain poorly understood. Our data indicated that SIRT6 protein and mRNA levels were reduced in islets from diabetic and aged mice. High concentrations of palmitate (PA) also led to a decrease in SIRT6 expression in MIN6 β-cells and resulted in cell dysfunction and apoptosis. Knockdown of Sirt6 caused an increase in cell apoptosis and impairment in insulin secretion in response to glucose in MIN6 cells even in the absence of PA exposure. Furthermore, overexpression of SIRT6 alleviated the palmitate-induced lipotoxicity with improved cell viability and increased glucose-stimulated insulin secretion. In summary, our data suggest that SIRT6 can protect against palmitate-induced β-cell dysfunction and apoptosis.

scholarly journals Long-term inhibition of protein tyrosine kinase impairs electrophysiologic activity and a rapid component of exocytosis in pancreatic β-cells

2005 ◽  
Vol 35 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Yu-Feng Zhao ◽  
Damien J Keating ◽  
Maria Hernandez ◽  
Dan Dan Feng ◽  
Yulong Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Protein Tyrosine ◽  
Cell Dysfunction ◽  
Genistein Treatment

Dysfunction of pancreatic β-cells is a fundamental feature in the pathogenesis of type 2 diabetes. As insulin receptor signaling occurs via protein tyrosine kinase (PTK), we investigated the role of PTK activity in the etiology of β-cell dysfunction by inhibiting PTK activity in primary cultured mouse pancreatic β-cells and INS-1 cells with genistein treatment over 24 h. Electrophysiologic recordings showed genistein treatment significantly attenuated ATP-sensitive K+ (KATP) and voltage-dependent Ca2+ currents, and depolarized the resting membrane potential in primary β-cells. When stimulated by high glucose, genistein-treated β-cells exhibited a time delay of both depolarization and Ca2+ influx, and were unable to fire action potentials, as well as displaying a reduced level of Ca2+ influx and a loss of Ca2+ oscillations. Semiquantitative PCR analysis revealed decreased expression of KATP and L-type Ca2+ channel mRNA in genistein-treated islets. PTK inhibition also significantly reduced the rapid component of secretory vesicle exocytosis, as indicated by membrane capacitance measurements, and this is likely to be due to the reduced Ca2+ current amplitude in these cells. These results illustrate that compromised PTK activity contributes to pancreatic β-cell dysfunction and may be involved in the etiology of type 2 diabetes.

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