scholarly journals Regulation of Gene Expression by Glucose in Pancreatic β-Cells (MIN6) via Insulin Secretion and Activation of Phosphatidylinositol 3′-Kinase

2000 ◽  
Vol 275 (46) ◽  
pp. 36269-36277 ◽  
Author(s):  
Gabriela da Silva Xavier ◽  
Aniko Varadi ◽  
Edward K. Ainscow ◽  
Guy A. Rutter
Keyword(s):  
Gene Expression ◽  
Insulin Secretion ◽  
Regulation Of Gene Expression ◽  
Phosphatidylinositol 3 Kinase ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Phosphatidylinositol 3

scholarly journals Mechanisms of Glucose-Induced Expression of Pancreatic-Derived Factor in Pancreatic β-Cells

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 672-680 ◽  
Author(s):  
Oumei Wang ◽  
Kun Cai ◽  
Shanshan Pang ◽  
Ting Wang ◽  
Dongfei Qi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Promoter Activation ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Phosphatidylinositol 3

Pancreatic-derived factor (PANDER) is a cytokine-like peptide highly expressed in pancreatic β-cells. PANDER was reported to promote apoptosis of pancreatic β-cells and secrete in response to glucose. Here we explored the effects of glucose on PANDER expression, and the underlying mechanisms in murine pancreatic β-cell line MIN6 and primary islets. Our results showed that glucose up-regulated PANDER mRNA and protein levels in a time- and dose-dependent manner in MIN6 cells and pancreatic islets. In cells expressing cAMP response element-binding protein (CREB) dominant-negative construct, glucose failed to induce PANDER gene expression and promoter activation. Treatment of the cells with calcium chelator [EGTA, 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA/AM)], the voltage-dependent Ca2+ channel inhibitor (nifedipine), the protein kinase A (PKA) inhibitor (H89), the protein kinase C (PKC) inhibitor (Go6976), or the MAPK kinase 1/2 inhibitor (PD98059), all significantly inhibited glucose-induced PANDER gene expression and promoter activation. Further studies showed that glucose induced CREB phosphorylation through Ca2+-PKA-ERK1/2 and Ca2+-PKC pathways. Thus, the Ca2+-PKA-ERK1/2-CREB and Ca2+-PKC-CREB signaling pathways are involved in glucose-induced PANDER gene expression. Wortmannin (phosphatidylinositol 3-kinase inhibitor), ammonium pyrrolidinedithiocarbamate (nuclear factor-κB inhibitor and nonspecific antioxidant), and N-acetylcysteine (antioxidant) were also found to inhibit glucose-induced PANDER promoter activation and gene expression. Because there is no nuclear factor-κB binding site in the promoter region of PANDER gene, these results suggest that phosphatidylinositol 3-kinase and reactive oxygen species be involved in glucose-induced PANDER gene expression. In conclusion, glucose induces PANDER gene expression in pancreatic β-cells through multiple signaling pathways. Because PANDER is expressed by pancreatic β-cells and in response to glucose in a similar way to those of insulin, PANDER may be involved in glucose homeostasis.

scholarly journals Class IA Phosphatidylinositol 3-Kinase in Pancreatic β Cells Controls Insulin Secretion by Multiple Mechanisms

2010 ◽  
Vol 12 (6) ◽  
pp. 619-632 ◽  
Author(s):  
Kazuma Kaneko ◽  
Kohjiro Ueki ◽  
Noriko Takahashi ◽  
Shinji Hashimoto ◽  
Masayuki Okamoto ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Phosphatidylinositol 3 Kinase ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Phosphatidylinositol 3

scholarly journals PKCλ regulates glucose-induced insulin secretion through modulation of gene expression in pancreatic β cells

2005 ◽  
Vol 115 (1) ◽  
pp. 138-145 ◽  
Author(s):  
Naoko Hashimoto ◽  
Yoshiaki Kido ◽  
Tohru Uchida ◽  
Tomokazu Matsuda ◽  
Kazuhisa Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Modulation Of Gene Expression

scholarly journals (-)-Leucophyllone, a Tirucallane Triterpenoid from Cornus walteri, Enhances Insulin Secretion in INS-1 Cells

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 431
Author(s):  
Dahae Lee ◽  
Ki Hyun Kim ◽  
Taesu Jang ◽  
Ki Sung Kang
Keyword(s):  
Insulin Secretion ◽  
Stem Bark ◽  
Insulin Receptor Substrate ◽  
Antidiabetic Agent ◽  
Liquid Chromatography Mass Spectrometry ◽  
Phosphatidylinositol 3 Kinase ◽  
Β Cells ◽  
Meoh Extract ◽  
Pancreatic Β Cells ◽  
Glucose Stimulated Insulin Secretion

Phytochemical examination of the MeOH extract from the stems and stem bark of Cornus walteri (Cornaceae) led to the isolation and verification of a tirucallane triterpenoid, (-)-leucophyllone, as a major component. Its structure was elucidated using NMR spectroscopy and liquid chromatography–mass spectrometry. The effect of (-)-leucophyllone on insulin secretion in INS-1 cells was investigated. (-)-Leucophyllone increased glucose-stimulated insulin secretion (GSIS) at concentrations showing no cytotoxic effect in rat INS-1 pancreatic β-cells. Moreover, we attempted to determine the mechanism of action of (-)-leucophyllone in the activation of insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1). Treatment of INS-1 cells with (-)-leucophyllone markedly increased the expression of these proteins. Our findings indicate the potential of (-)-leucophyllone as an antidiabetic agent.

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.

scholarly journals Insulin Secretion Induced by Glucose-dependent Insulinotropic Polypeptide Requires Phosphatidylinositol 3-Kinase γ in Rodent and Human β-Cells

2014 ◽  
Vol 289 (46) ◽  
pp. 32109-32120 ◽  
Author(s):  
Jelena Kolic ◽  
Aliya F. Spigelman ◽  
Alannah M. Smith ◽  
Jocelyn E. Manning Fox ◽  
Patrick E. MacDonald
Keyword(s):  
Insulin Secretion ◽  
Phosphatidylinositol 3 Kinase ◽  
Β Cells ◽  
Phosphatidylinositol 3

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.

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