scholarly journals Astragalus polysaccharide improve the proliferation and insulin secretion of mouse pancreatic β cells induced by high glucose and palmitic acid partially through promoting miR-136-5p and miR-149-5p expression

Bioengineered ◽  
2021 ◽  
Author(s):  
Shifang Deng ◽  
Lei Yang ◽  
Ke Ma ◽  
Wei Bian
Keyword(s):  
Insulin Secretion ◽  
Palmitic Acid ◽  
High Glucose ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Astragalus Polysaccharide

scholarly journals Protective Effect of Siegesbeckia orientalis on Pancreatic β-Cells under High Glucose-Induced Glucotoxicity

2021 ◽  
Vol 11 (22) ◽  
pp. 10963
Author(s):  
Chi-Chang Chang ◽  
Jer-Yiing Houng ◽  
Shih-Wei Wang ◽  
Chin-Feng Hsuan ◽  
Yung-Chuan Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Insulin Secretion ◽  
Protective Effect ◽  
Normal Level ◽  
High Glucose ◽  
Glucose Concentration ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Siegesbeckia Orientalis

The glucotoxicity caused by long-term exposure of β-cells to high glucose (HG) conditions may lead to the generation of more reactive oxygen species (ROS), reduce the activity of antioxidant enzymes, cause cell damage and apoptosis, and induce insulin secretion dysfunction. Siegesbeckia orientalis linne is a traditional folk herbal medicine used to treat snake bites, rheumatoid arthritis, allergies, and immune deficiencies. In this study, we evaluated the protective effect of S. orientalis ethanol extract (SOE) on cell death and oxidative stress in RIN-m5f pancreatic β-cells stimulated by two HG concentrations (50–100 mM). In the cell viability assay, SOE could significantly increase the survival rate of pancreatic β-cells under HG-induced conditions. For the oxidative stress induced by HG condition, the treatment of SOE effectively reduced the ROS formation, increased the content of intracellular glutathione, and up-regulated the expression of antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase. As a result, the SOE treatment could decrease the glucotoxicity-mediated oxidative damage on RIN-m5F β-cells. Moreover, SOE had the function of regulating insulin secretion in pancreatic β-cells under different HG-mediated conditions. It could decrease the increasing intracellular insulin secretion under the low glucose concentration to normal level; while increase the decreasing intracellular insulin secretion under the relatively high glucose concentration to normal level. Taken together, this study suggests that SOE has a protective effect on pancreatic β-cells under the HG-stimulated glucotoxic environment.

Crucial roles of neuronatin in insulin secretion and high glucose-induced apoptosis in pancreatic β-cells

2008 ◽  
Vol 20 (5) ◽  
pp. 907-915 ◽  
Author(s):  
Myung Kuk Joe ◽  
Hyo Jung Lee ◽  
Young Ho Suh ◽  
Kyu Lee Han ◽  
Joo Hyun Lim ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
High Glucose ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Induced Apoptosis

scholarly journals Mitigation of Glucolipotoxicity-Induced Apoptosis, Mitochondrial Dysfunction, and Metabolic Stress by N-Acetyl Cysteine in Pancreatic β-Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 239 ◽  
Author(s):  
Arwa Alnahdi ◽  
Annie John ◽  
Haider Raza
Keyword(s):  
Energy Metabolism ◽  
Palmitic Acid ◽  
Mitochondrial Dysfunction ◽  
High Glucose ◽  
High Energy ◽  
Metabolic Adaptation ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Mitochondrial Energy Metabolism ◽  
Acetyl Cysteine

Glucolipotoxicity caused by hyperglycemia and hyperlipidemia are the common features of diabetes-induced complications. Metabolic adaptation, particularly in energy metabolism; mitochondrial dysfunction; and increased inflammatory and oxidative stress responses are considered to be the main characteristics of diabetes and metabolic syndrome. However, due to various fluctuating endogenous and exogenous stimuli, the precise role of these factors under in vivo conditions is not clearly understood. In the present study, we used pancreatic β-cells, Rin-5F, to elucidate the molecular and metabolic changes in glucolipotoxicity. Cells treated with high glucose (25 mM) and high palmitic acid (up to 0.3 mM) for 24 h exhibited increased caspase/poly-ADP ribose polymerase (PARP)-dependent apoptosis followed by DNA fragmentation, alterations in mitochondrial membrane permeability, and bioenergetics, accompanied by alterations in glycolytic and mitochondrial energy metabolism. Our results also demonstrated alterations in the expression of mammalian target of rapamycin (mTOR)/5′ adenosine monophosphate-activated protein kinase (AMPK)-dependent apoptotic and autophagy markers. Furthermore, pre-treatment of cells with 10 mM N-acetyl cysteine attenuated the deleterious effects of high glucose and high palmitic acid with improved cellular functions and survival. These results suggest that the presence of high energy metabolites enhance mitochondrial dysfunction and apoptosis by suppressing autophagy and adapting energy metabolism, mediated, at least in part, via enhanced oxidative DNA damage and mTOR/AMPK-dependent cell signaling.

scholarly journals PRMT4 is involved in insulin secretion via the methylation of histone H3 in pancreatic β cells

2015 ◽  
Vol 54 (3) ◽  
pp. 315-324 ◽  
Author(s):  
Joong Kwan Kim ◽  
Yongchul Lim ◽  
Jung Ok Lee ◽  
Young-Sun Lee ◽  
Nam Hee Won ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Secretion ◽  
High Glucose ◽  
Histone H3 ◽  
Insulin Gene ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Protein Arginine Methyltransferases ◽  
Insulin Synthesis ◽  
Insulin Gene Expression

The relationship between protein arginine methyltransferases (PRMTs) and insulin synthesis in β cells is not yet well understood. In the present study, we showed that PRMT4 expression was increased in INS-1 and HIT-T15 pancreatic β cells under high-glucose conditions. In addition, asymmetric dimethylation of Arg17 in histone H3 was significantly increased in both cell lines in the presence of glucose. The inhibition or knockdown of PRMT4 suppressed glucose-induced insulin gene expression in INS-1 cells by 81.6 and 79% respectively. Additionally, the overexpression of mutant PRMT4 also significantly repressed insulin gene expression. Consistently, insulin secretion induced in response to high levels of glucose was decreased by both PRMT4 inhibition and knockdown. Moreover, the inhibition of PRMT4 blocked high-glucose-induced insulin gene expression and insulin secretion in primary pancreatic islets. These results indicate that PRMT4 might be a key regulator of high-glucose-induced insulin secretion from pancreatic β cells via H3R17 methylation.

scholarly journals Glucose-Dependent Changes in SNARE Protein Levels in Pancreatic β-Cells

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1290-1299 ◽  
Author(s):  
Benjamín Torrejón-Escribano ◽  
Jessica Escoriza ◽  
Eduard Montanya ◽  
Juan Blasi
Keyword(s):  
Insulin Secretion ◽  
Protein Expression ◽  
High Glucose ◽  
Glucose Concentration ◽  
Snare Proteins ◽  
High Glucose Concentration ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
In Vivo Models ◽  
Insulin Granule

Abstract Prolonged exposure to high glucose concentration alters the expression of a set of proteins in pancreatic β-cells and impairs their capacity to secrete insulin. The cellular and molecular mechanisms that lie behind this effect are poorly understood. In this study, three either in vitro or in vivo models (cultured rat pancreatic islets incubated in high glucose media, partially pancreatectomized rats, and islets transplanted to streptozotozin-induced diabetic mice) were used to evaluate the dependence of the biological model and the treatment, together with the cell location (insulin granule or plasma membrane) of the affected proteins and the possible effect of sustained insulin secretion, on the glucose-induced changes in protein expression. In all three models, islets exposed to high glucose concentrations showed a reduced expression of secretory granule-associated vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins synaptobrevin/vesicle-associated membrane protein 2 and cellubrevin but minor or no significant changes in the expression of the membrane-associated target-SNARE proteins syntaxin1 and synaptosomal-associated protein-25 and a marked increase in the expression of synaptosomal-associated protein-23 protein. The inhibition of insulin secretion by the L-type voltage-dependent calcium channel nifedipine or the potassium channel activator diazoxide prevented the glucose-induced reduction in islet insulin content but not in vesicle-SNARE proteins, indicating that the granule depletion due to sustained exocytosis was not involved in the changes of protein expression induced by high glucose concentration. Altogether, the results suggest that high glucose has a direct toxic effect on the secretory pathway by decreasing the expression of insulin granule SNARE-associated proteins.

scholarly journals JunD Regulates Pancreatic β-Cells Function by Altering Lipid Accumulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kexin Wang ◽  
Yixin Cui ◽  
Peng Lin ◽  
Zhina Yao ◽  
Yu Sun
Keyword(s):  
Gene Expression ◽  
Insulin Secretion ◽  
Lipid Metabolism ◽  
Palmitic Acid ◽  
Lipid Accumulation ◽  
Activator Protein 1 ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Intracellular Lipid Accumulation ◽  
Glucose Stimulated Insulin Secretion

The impairment of pancreatic β-cells function is partly caused by lipotoxicity, which aggravates the development of type 2 diabetes mellitus. Activator Protein 1 member JunD modulates apoptosis and oxidative stress. Recently, it has been found that JunD regulates lipid metabolism in hepatocytes and cardiomyocytes. Here, we studied the role of JunD in pancreatic β-cells. The lipotoxic effects of palmitic acid on INS-1 cells were measured, and JunD small-interfering RNA was used to assess the effect of JunD in regulating lipid metabolism and insulin secretion. The results showed that palmitic acid stimulation induced the overexpression of JunD, impaired glucose-stimulated insulin secretion, and increased intracellular lipid accumulation of β-cells. Moreover, the gene expression involved in lipid metabolism (Scd1, Fabp4, Fas, Cd36, Lpl, and Plin5) was upregulated, while gene expression involved in the pancreatic β-cells function (such as Pdx1, Nkx6.1, Glut2, and Irs-2) was decreased. Gene silencing of JunD reversed the lipotoxic effects induced by PA on β-cells. These results suggested that JunD regulated the function of pancreatic β-cells by altering lipid accumulation.

Congenital hyperinsulinism due to compound heterozygous mutations in ABCC8 responsive to diazoxide therapy

2020 ◽  
Vol 33 (5) ◽  
pp. 671-674
Author(s):  
Tashunka Taylor-Miller ◽  
Jayne Houghton ◽  
Paul Munyard ◽  
Yadlapalli Kumar ◽  
Clinda Puvirajasinghe ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Compound Heterozygous ◽  
Congenital Hyperinsulinism ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Newborn Period ◽  
Case Presentation ◽  
Male Baby ◽  
Common Causes ◽  
Compound Heterozygous Mutations

AbstractBackgroundCongenital hyperinsulinism (CHI), a condition characterized by dysregulation of insulin secretion from the pancreatic β cells, remains one of the most common causes of hyperinsulinemic, hypoketotic hypoglycemia in the newborn period. Mutations in ABCC8 and KCNJ11 constitute the majority of genetic forms of CHI.Case presentationA term macrosomic male baby, birth weight 4.81 kg, born to non-consanguineous parents, presented on day 1 of life with severe and persistent hypoglycemia. The biochemical investigations confirmed a diagnosis of CHI. Diazoxide was started and progressively increased to 15 mg/kg/day to maintain normoglycemia. Sequence analysis identified compound heterozygous mutations in ABCC8 c.4076C>T and c.4119+1G>A inherited from the unaffected father and mother, respectively. The mutations are reported pathogenic. The patient is currently 7 months old with a sustained response to diazoxide.ConclusionsBiallelic ABCC8 mutations are known to result in severe, diffuse, diazoxide-unresponsive hypoglycemia. We report a rare patient with CHI due to compound heterozygous mutations in ABCC8 responsive to diazoxide.

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