scholarly journals Insulinotropic Activity of Standardized Methanolic Extracts of Ficus deltoidea from Seven Varieties

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Nurshieren Yahaya ◽  
Nur Sumirah Mohd Dom ◽  
Zainah Adam ◽  
Muhajir Hamid
Keyword(s):  
Insulin Secretion ◽  
Cell Line ◽  
Pancreatic Beta Cells ◽  
Ficus Deltoidea ◽  
Viability Assay ◽  
Methanolic Extracts ◽  
Agonist And Antagonist ◽  
Viability Percentage ◽  
Independent Varieties ◽  
Insulinotropic Effect

Ficus deltoidea is a traditional medicinal plant that has been proven to show antidiabetic effects. This study focus is to assess the insulin secretion activity of Ficus deltoidea standardized methanolic extracts from seven independent varieties and mechanisms that underlie the insulin secretion action of the extracts. The cytotoxicity of Ficus deltoidea extracts was tested using viability assay. The insulin secretion assay was carried out by treating clonal BRIN BD11 cell line with standardized methanolic Ficus deltoidea extracts or glybenclamide. The clonal BRIN BD11 cell was also treated with insulin agonist and antagonist to elucidate the insulin secretion mechanism. Only the viability percentage for Ficus deltoidea var. kunstleri and intermedia was identified to be toxic at 500 and 1000 μg/ml (P<0.001). The insulin secretion for Ficus deltoidea var. deltoidea, angustifolia, and motleyana was dose-dependent; further evaluation suggested that Ficus deltoidea var. trengganuensis was involved in KATP-independent pathway. This study suggests that standardized methanolic extracts of Ficus deltoidea varieties have an insulinotropic effect on clonal BRIN BD11 cell line and can be utilized as a modern candidate of antidiabetic agents targeting the escalation for insulin secretion from pancreatic beta cells.

scholarly journals A comparative study of amino acid consumption by rat islet cells and the clonal beta-cell line BRIN-BD11 - the functional significance of L-alanine

2003 ◽  
Vol 179 (3) ◽  
pp. 447-454 ◽  
Author(s):  
G Dixon ◽  
J Nolan ◽  
N McClenaghan ◽  
PR Flatt ◽  
P Newsholme
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Line ◽  
Islet Cells ◽  
Beta Cell Line ◽  
Acid Consumption ◽  
Glutamine Consumption ◽  
Order Of Magnitude ◽  
Stimulus Secretion Coupling ◽  
Insulinotropic Effect

Evidence has been published that L -alanine may, under appropriate conditions, promote insulin secretion in normal rodent islets and various beta cell lines. Previous results utilising the clonal beta-cell line BRIN-BD11, demonstrated that alanine dramatically elevated insulin release by a mechanism requiring oxidative metabolism. We demonstrate in this paper that addition ofL -alanine had an insulinotropic effect in dispersed primary islet cells. Addition of D -glucose increasedL -alanine consumption in both BRIN-BD11 cells and primary islet cells.L -glutamine consumption in the BRIN-BD11 cell line and primary rat islets was also determined. The consumption rate was in line with that previously reported for cells of the immune system and other glutamine-utilising cells or tIssues. However,L -alanine consumption was at least an order of magnitude higher thanL -glutamine consumption. The metabolism ofL -alanine in the beta-cell may result in stimulation of insulin secretion via generation of metabolic stimulus secretion coupling factors such asL -glutamate.

scholarly journals High dose of histone deacetylase inhibitors affects insulin secretory mechanism of pancreatic beta cell line

2018 ◽  
Vol 52 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Eiji Yamato
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Line ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Pancreatic Beta Cell ◽  
High Dose ◽  
Min6 Cells ◽  
Beta Cell Line ◽  
High Doses

Abstract Objective. Histone deacytylase inhibitors (HDACis) inhibit the deacetylation of the lysine residue of proteins, including histones, and regulate the transcription of a variety of genes. Recently, HDACis have been used clinically as anti-cancer drugs and possible anti-diabetic drugs. Even though HDACis have been proven to protect the cytokine-induced damage of pancreatic beta cells, evidence also shows that high doses of HDACis are cytotoxic. In the present study, we, therefore, investigated the eff ect of HDACis on insulin secretion in a pancreatic beta cell line. Methods. Pancreatic beta cells MIN6 were treated with selected HDACis (trichostatin A, TSA; valproic acid, VPA; and sodium butyrate, NaB) in medium supplemented with 25 mM glucose and 13% heat-inactivated fetal bovine serum (FBS) for indicated time intervals. Protein expression of Pdx1 and Mafa in MIN6 cells was demonstrated by immunohistochemistry and immunocytochemistry, expression of Pdx1 and Mafa genes was measured by quantitative RT-PCR method. Insulin release from MIN6 cells and insulin cell content were estimated by ELISA kit. Superoxide production in MIN6 cells was measured using a Total ROS/Superoxide Detection System. Results. TSA, VPA, and NaB inhibited the expression of Pdx1 and Mafa genes and their products. TSA treatment led to beta cell malfunction, characterized by enhanced insulin secretion at 3 and 9 mM glucose, but impaired insulin secretion at 15 and 25 mM glucose. Th us, TSA induced dysregulation of the insulin secretion mechanism. TSA also enhanced reactive oxygen species production in pancreatic beta cells. Conclusions. Our results showed that HDACis caused failure to suppress insulin secretion at low glucose concentrations and enhance insulin secretion at high glucose concentrations. In other words, when these HDACis are used clinically, high doses of HDACis may cause hypoglycemia in the fasting state and hyperglycemia in the fed state. When using HDACis, physicians should, therefore, be aware of the capacity of these drugs to modulate the insulin secretory capacity of pancreatic beta cells.

scholarly journals Effects of High Glucose Levels and Glycated Serum on GIP Responsiveness in the Pancreatic Beta Cell Line HIT-T15

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
Fabrizio Montecucco ◽  
Giorgio Luciano Viviani
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Line ◽  
High Glucose ◽  
Intracellular Signaling ◽  
Pancreatic Beta Cells ◽  
Pancreatic Beta Cell ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Beta Cell Line

Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone produced in the gastrointestinal tract that stimulates glucose dependent insulin secretion. Impaired incretin response has been documented in diabetic patients and was mainly related to the inability of the pancreatic beta cells to secrete insulin in response to GIP. Advanced Glycation End Products (AGEs) have been shown to play an important role in pancreatic beta cell dysfunction. The aim of this study is to investigate whether the exposure to AGEs can induce GIP resistance in the pancreatic beta cell line HIT-T15. Cells were cultured for 5 days in low (CTR) or high glucose (HG) concentration in the presence of AGEs (GS) to evaluate the expression of GIP receptor (GIPR), the intracellular signaling activated by GIP, and secretion of insulin in response to GIP. The results showed that incubation with GS alone altered intracellular GIP signaling and decreased insulin secretion as compared to CTR. GS in combination with HG reduced the expression of GIPR and PI3K and abrogated GIP-induced AKT phosphorylation and GIP-stimulated insulin secretion. In conclusion, we showed that treatment with GS is associated with the loss of the insulinotropic effect of GIP in hyperglycemic conditions.

scholarly journals Stable overexpression of the glucose-6-phosphatase catalytic subunit attenuates glucose sensitivity of insulin secretion from a mouse pancreatic beta-cell line

2000 ◽  
Vol 164 (3) ◽  
pp. 307-314 ◽  
Author(s):  
K Iizuka ◽  
H Nakajima ◽  
A Ono ◽  
K Okita ◽  
J Miyazaki ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Line ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucose Sensor ◽  
Pancreatic Beta Cell ◽  
Catalytic Subunit ◽  
Beta Cell Line ◽  
Glucose Stimulated Insulin Secretion

Glucose-6-phosphatase (G-6-Pase) hydrolyzes glucose-6-phosphate to glucose, reciprocal with the so-called glucose sensor, glucokinase, in pancreatic beta cells. To study the role of G-6-Pase in glucose-stimulated insulin secretion from beta cells, we have introduced rat G-6-Pase catalytic subunit cDNA and have established permanent clones with 3-, 7- and 24-fold G-6-Pase activity of the mouse beta-cell line, MIN6. In these clones, glucose usage and ATP production in the presence of 5.5 or 25 mM glucose were reduced, and glucose-stimulated insulin secretion was decreased in proportion to the increased G-6-Pase activity. In addition, insulin secretory capacity in response to d-fructose and pyruvate was unchanged; however, 25 mM glucose-stimulated insulin secretion and intracellular calcium response were completely inhibited. In the clone with 24-fold G-6-Pase activity, changes in intracellular NAD(P)H autofluorescence in response to 25 mM glucose were reduced, but the changes with 20 mM fructose and 20 mM pyruvate were not altered. Stable overexpression of G-6-Pase in beta cells resulted in attenuation of the overall glucose-stimulated metabolic responses corresponding to the degree of overexpression. This particular experimental manipulation shows that the possibility exists of modulating glucose-stimulated insulin release by thoroughly altering glucose cycling at the glucokinase/G-6-Pase step.

Resveratrol attenuates hIAPP amyloid formation and restores the insulin secretion ability in hIAPP-INS1 cell line via enhancing autophagy

2019 ◽  
Vol 97 (2) ◽  
pp. 82-89 ◽  
Author(s):  
Wu Lv ◽  
Jialin Zhang ◽  
Ao Jiao ◽  
Bowen Wang ◽  
Baomin Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Line ◽  
Islet Transplantation ◽  
Pancreatic Beta Cells ◽  
Chemical Structure ◽  
Amyloid Deposition ◽  
Amyloid Formation ◽  
Islet Amyloid

It has been proved that human islet amyloid polypeptide (hIAPP), the main constituent of islet amyloid deposition, is one of the important factors that can induce type 2 diabetes or graft failure after islet transplantation. As there is no research on whether resveratrol degrading the amyloid deposition by its special chemical structure or enhancing autophagy had been published, we decided to detect the function of resveratrol in degrading the amyloid deposition in pancreatic beta cells. We established stable hIAPP-INS1 cell line via transfecting INS1 cells by lentivirus that overexpresses hIAPP. Our research demonstrates that amyloid deposition existed in hIAPP-INS1 cell by the thioflavin S fluorescent staining, meanwhile the function of insulin secretion of hIAPP-INS1 cells was decreased significantly (p < 0.01). After treatment with resveratrol (20 μM) for 24 h, amyloid deposition in hIAPP-INS1 cells was decreased significantly, and the insulin secretion was restored significantly (p < 0.01). Once inhibited the autophagy of hIAPP-INS1 cells by 3-methyladenine for 24 h, resveratrol does not effectively remove hIAPP deposits again, and cannot improve the function of insulin secretion. These results provide a novel thought that resveratrol can degrade the amyloid deposition in type 2 diabetes and the graft after islet transplantation.

scholarly journals The Microtubule-Associated Protein Tau and Its Relevance for Pancreatic Beta Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Magdalena Maj ◽  
Gregor Hoermann ◽  
Sazan Rasul ◽  
Wolfgang Base ◽  
Ludwig Wagner ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Line ◽  
Beta Cells ◽  
Islets Of Langerhans ◽  
Pancreatic Beta Cells ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
Overexpressing Cell ◽  
Secretion Rates

Structural and biochemical alterations of the microtubule-associated protein tau (MAPT) are associated with degenerative disorders referred to as tauopathies. We have previously shown that MAPT is present in human islets of Langerhans, human insulinomas, and pancreatic beta-cell line models, with biophysical similarities to the pathological MAPT in the brain. Here, we further studied MAPT in pancreatic endocrine tissue to better understand the mechanisms that lead to functional dysregulation of pancreatic beta cells. We found upregulation of MAPT protein expression in human insulinomas when compared to human pancreatic islets of Langerhans and an imbalance between MAPT isoforms in insulinomas tissue. We cloned one 3-repeat domain MAPT and transduced this into a beta-cell derived rodent cell line Rin-5F. Proliferation experiments showed higher growth rates and metabolic activities of cells overexpressing MAPT protein. We observed that a MAPT overexpressing cell line demonstrates altered insulin transcription, translation, and insulin secretion rates. We found the relative insulin secretion rates were significantly decreased in a MAPT overexpressing cell line and these findings could be confirmed using partial MAPT knock-down cell lines. Our findings support that MAPT may play an important role in insulin granule trafficking and indicate the importance of balanced MAPT phosphorylation and dephosphorylation for adequate insulin release.

Murine insulinoma cell line with normal glucose-regulated insulin secretion

Diabetes ◽  
1993 ◽  
Vol 42 (6) ◽  
pp. 901-907 ◽  
Author(s):  
S. Efrat ◽  
M. Leiser ◽  
M. Surana ◽  
M. Tal ◽  
D. Fusco-Demane ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Line ◽  
Insulinoma Cell ◽  
Insulinoma Cell Line ◽  
Normal Glucose
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