Effect of Glucose Metabolism-Associated Protein-1 on Exendin-4-Treated Pancreatic Islet Cell Function

2020 ◽  
Vol 10 (7) ◽  
pp. 1015-1021
Author(s):  
Jing Feng ◽  
Cuiwen Kong ◽  
Min Wang ◽  
Yingchuan Xu ◽  
Yingwei Chang
Keyword(s):  
Cell Proliferation ◽  
Glucose Metabolism ◽  
Islet Cell ◽  
Caspase 3 ◽  
Cell Function ◽  
Islet Cells ◽  
Control Group ◽  
Sod Activity ◽  
Fas L ◽  
Islet Cell Function

Exendin-4 regulates blood sugar. Glucose metabolism-associated protein-1 (GMRP-1) regulates islet cell function. Therefore, this paper intends to analyze the effect of GMRP-1 on Exendin-4treated islet cells. The islet cell MIN6 cells were separated into control group, Exendin-4 group, GMRP-1 overexpressing+ Exendin-4 group, and GMRP-1 siRNA+ Exendin-4 group followed by analysis of the expression of GMRP-1 by quantitative real-time PCR and Western blot, cell proliferation by MTT, cell apoptosis by flow cytometry, Bcl-2, Bax, Fas and Fas-L expression by real-time PCR, as well as caspase-3 activity, reactive oxygen species (ROS) and superoxide dismutase (SOD) activity. Exendin-4 and GMRP-1 overexpression+ Exendin-4 significantly increased GMRP-1 expression and promoted cell proliferation, decreased apoptotic rate and Caspase-3 activity, increased Bcl-2 and Fas-L expression, reduced Fas and Bax expression, as well as decreased ROS generation and increased SOD activity (P < 0 05), and the changes in GMRP-1 overexpression+ Exendin-4 group was more significant (P < 0 01). However, GMRP-1 siRNA+ Exendin-4 group significantly down-regulated GMRP-1 expression, decreased MIN6 cell prolifer- ation, increased cell apoptosis and Caspase-3 activity, decreased Bcl-2 and Fas-L expression, elevated Fas and Bax expression, increased ROS content and decreased SOD activity compared to control group and Exendin-4 group (P < 0 05). Up-regulation of GMRP-1 expression promoted Exendin-4-induced proliferation and inhibited apoptosis of islet cells. Down-regulation of GMRP-1 expression reversed Exendin-4's effect on islet cells.

scholarly journals Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood

2002 ◽  
pp. 129-141 ◽  
Author(s):  
H Hui ◽  
R Perfetti
Keyword(s):  
Islet Cell ◽  
Glucose Transporter ◽  
Cell Function ◽  
Islet Cells ◽  
Cell Physiology ◽  
Islet Amyloid ◽  
Dominant Form ◽  
Insulin Promoter ◽  
Dual Action ◽  
Islet Cell Function

Pancreas duodenum homeobox-1 (PDX-1) (also known as insulin promoter factor-1, islet/duodenum homeobox-1, somatostatin transactivating factor-1, insulin upstream factor-1 and glucose-sensitive factor) is a transcription factor encoded by a Hox-like homeodomain gene. In humans and other animal species, the embryonic development of the pancreas requires PDX-1, as demonstrated by the identification of an individual with pancreatic agenesis resulting from a mutation that impaired the transcription of a functionally active PDX-1 protein. In adult subjects, PDX-1 is essential for normal pancreatic islet function as suggested by its regulatory action on the expression of a number of pancreatic genes, including insulin, somatostatin, islet amyloid polypeptide, the glucose transporter type 2 and glucokinase. Furthermore, heterozygous mutations of PDX-1 have been linked to a type of autosomal dominant form of diabetes mellitus known as maturity onset diabetes of the young type 4. The dual action of PDX-1, as a differentiation factor during embryogenesis and as a regulator of islet cell physiology in mature islet cells, underscores the unique role of PDX-1 in health and disease of the human endocrine pancreas.

Effect of Silencing Information Regulator on Islet β Cells in High Glucose Environment Through Regulation of Phosphatidylinositol 3 Kinase (PI3K)/Protein Kinase B (AKT)/Nuclear Factor-κ-Gene Binding Pathway

2021 ◽  
Vol 11 (8) ◽  
pp. 1624-1629
Author(s):  
Nali Liu ◽  
Beijing Zhu ◽  
Xin Wei
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
High Glucose ◽  
Islet Cell ◽  
Control Group ◽  
Diabetic Patients ◽  
Phosphatidylinositol 3 Kinase ◽  
Sod Activity ◽  
Sirt1 Expression ◽  
Cell Supernatant

Islet β-cell regeneration is beneficial for treating diabetic patients. Silencing information regulator (SIRT1) has a regulatory role in endocrine diseases. However, SIRT1’s role in islet β cells remains unclear. MIN6 cells were cultured and assigned into control group, high glucose group, and SIRT1 group (treated with SIRT1 agonist, Resveratrol) followed by analysis of SIRT1 expression by Real time PCR and ELISA, cell proliferation by MTT assay, apoptosis activity by Caspase3 activity kit, secretion of TNF-α and IL-2 by ELISA, insulin secretion, ROS and SOD generation and expression of PI3K/Akt/NF-κB signaling by Western blot. SIRT1 mRNA was decreased in high glucose environment and its secretion in cell supernatant was reduced, with inhibited cell proliferation, increased Caspase3 activity and secretion of TNF-α and IL-2, decreased insulin secretion and SOD activity, increased ROS content, pAKT phosphorylation and NF-κB expression. Resveratrol significantly promoted SIRT1 expression and cell proliferation, decreased Caspase3 activity and secretion of TNF-α and IL-2, increased insulin secretion and SOD activity, as well as decreased ROS content, pAKT phosphorylation and NF-κB expression (P <0.05). SIRT1 is decreased in high glucose environment, and SIRT1 expression can inhibit islet cell apoptosis, inhibit oxidative stress and inflammation, and promote islet cell proliferation and insulin secretion by regulating PI3K/Akt/NF-κB signaling.

scholarly journals IL-6 Promotes Islet β-Cell Dysfunction in Rat Collagen-Induced Arthritis

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Huan Jin ◽  
Yaogui Ning ◽  
Haotong Zhou ◽  
Youlian Wang
Keyword(s):  
Glucose Metabolism ◽  
Caspase 3 ◽  
Islet Cells ◽  
Type Ii Collagen ◽  
Intradermal Injection ◽  
Control Group ◽  
Collagen Induced Arthritis ◽  
Abnormal Glucose Metabolism ◽  
Pancreas Islet ◽  
Related Enzyme

The aim of this study was to explore the possible mechanism of rheumatoid arthritis- (RA-) related abnormal glucose metabolism. The model of collagen-induced arthritis (CIA) was established by intradermal injection of type II collagen into Wistar rats; complete Freund’s adjuvant injections were used as the control group. Fasting plasma glucose (FBG) was measured by the glucose oxidase method. Fasting insulin (FIns) and the expressions of IL-6 were detected by ELISA. Islet caspase-3 was examined by immunohistochemistry. On day 17 after immunization, FBG of the CIA group showed an elevated FBG value compared with the control group. Meanwhile, the FIns of group CIA was lower when compared with the control group. Interestingly, the inflammatory cytokine IL-6 expression was significantly increased when compared with the control group. As expected, the abnormal glucose metabolism was accompanied by the increased IL-6 expression. Furthermore, in line with the upregulated IL-6 expression, the apoptosis related enzyme caspase-3 was also markedly increased. These data showed that the elevated FBG in CIA may be associated with the reduced FIns level secondary to the overapoptosis of pancreas islet cells induced by IL-6.

1774-P: Neurally Mediated Prandial Islet-Cell Function Is Glucose-Independent and Preserved after Gastric Bypass and Sleeve Gastrectomy

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1774-P
Author(s):  
HENRI HONKA ◽  
ANAS M. AL ZUBAIDI ◽  
RALPH A. DEFRONZO ◽  
AMALIA GASTALDELLI ◽  
MARZIEH SALEHI
Keyword(s):  
Gastric Bypass ◽  
Sleeve Gastrectomy ◽  
Islet Cell ◽  
Cell Function ◽  
Islet Cell Function

Effects of Papaya Leaf Extract (Carica papaya L.) on Cellular Proliferation and Apoptosis in Cervical Cancer Mice Model

2019 ◽  
Vol 17 (5) ◽  
pp. 265-275
Author(s):  
Y. Peristiowati ◽  
Y. Puspitasari ◽  
Indasah
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Hela Cells ◽  
Leaf Extract ◽  
Caspase 3 ◽  
Methanol Extract ◽  
Negative Control ◽  
Proliferation Index ◽  
Control Group ◽  
P53 Expression

This study is aimed at analyzing the anticancer properties of papaya leaf extract, specifically the inhibition of cell proliferation and apoptotic induction through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 pathways. Twenty-five mice (Mus musculus), aged 2 months and weighing 20–30 g, was injected with 0.5 mg dexamethasone for 7 days. The mice were then injected intracutaneously with 1 ml of HeLa cells (8 × 106 HeLa cells/microliter). The mice were divided into five groups (5 each): negative control (P1) (5% CMC-Na, sodium carboxymethyl cellulose), treatment II (225 mg/kg BW (body weight) papaya leaves methanol extract), treatment III (450 mg/kg BW), treatment IV (750 mg/kg BW), and treatment PV (2 mg alcohol anticancer drug). Papaya leaf extract treatments were applied for 2 weeks. Then, the tumor tissue was isolated for hematoxylin and eosin staining. Immunohistochemical imaging was used to detect Ki-67, caspase-3, NF-κB, and p53 expression. Further analysis was undertaken using the ImmunoRatio software program. The results indicated that administration of papaya leaf methanol extract significantly increased the expression of NF-κB and p53 at a dose of 450 mg/kg BW. Our results also showed that the mice treated with 450 mg of papaya leaf extract per kg of BW (P3) had the largest increase of caspase-3 expression compared to the negative control group. Papaya leaf ethanol extract decreased the cancer cell proliferation index and increased apoptosis of cancer cells in animal models of cervical cancer; it may also work to increase NF-kB expression and expression of the p53 gene.

Effects of l-leucine, its 2-keto acid metabolite and its nonmetabolized analogue on rat tumoral islet cell function

1988 ◽  
Vol 1 (1) ◽  
pp. 69-76 ◽  
Author(s):  
V. Leclercq-Meyer ◽  
J. Marchand ◽  
A. Sener ◽  
F. Blachier ◽  
W. J. Malaisse
Keyword(s):  
Insulin Release ◽  
Cell Function ◽  
Islet Cells ◽  
Adenine Nucleotides ◽  
Secretory Response ◽  
Acid Metabolite ◽  
Dual Effect ◽  
Islet Cell Function ◽  
Insulinoma Cells ◽  
Stimulation Of

ABSTRACT l-Leucine and 2-ketoisocaproate stimulated insulin release from perifused rat tumoral islet cells (RINm5F line). The secretory response coincided with an increase in the intracellular ATP/ADP ratio, a stimulation of 45Ca outflow from cells perifused in the presence of extracellular Ca2+, and an increase in 32P efflux from cells prelabelled with radioactive orthophosphate. In contrast to d-glucose, however, l-leucine or 2-ketoisocaproate failed to decrease 86Rb outflow, to inhibit 45Ca outflow from cells perifused in the absence of Ca2+ and to enhance the labelling of inositol-containing phospholipids in cells exposed to myo-[2-3H]inositol. These findings suggest that d-glucose, l-leucine and 2-ketoisocaproate exert dissimilar effects on the subcellular distribution of adenine nucleotides and/or 86Rb. The nonmetabolized analogue of l-leucine, 2-aminobicyclo-[2.2.1]heptane-2-carboxylic acid (BCH), also caused an initial stimulation of insulin release and 32P efflux, but this was soon followed by a severe and irreversible inhibition of insulin output, associated with a permanent enhancement of 86Rb outflow. The dual ionic and secretory response to BCH is interpreted in the light of its dual effect on the catabolism of endogenous amino and fatty acids, and raises the view that BCH could be used to interfere with the function of insulinoma cells.

SBP-101 Produces Atrophy of the Exocrine Pancreas and Exocrine Pancreatic Insufficiency while Preserving Islet Cell Function in Dogs

2017 ◽  
Vol 152 (5) ◽  
pp. S901
Author(s):  
Michael Walker ◽  
Suzanne Gagnon ◽  
Andy Kiorpes ◽  
Michael Cullen ◽  
Jan Wiegand ◽  
...  
Keyword(s):  
Exocrine Pancreas ◽  
Islet Cell ◽  
Cell Function ◽  
Pancreatic Insufficiency ◽  
Exocrine Pancreatic Insufficiency ◽  
Islet Cell Function

Effects of glucose and d-3-hydroxybutyrate on human pancreatic islet cell function

1985 ◽  
Vol 68 (5) ◽  
pp. 567-572 ◽  
Author(s):  
C. J. Rhodes ◽  
I. L. Campbell ◽  
T. M. Szopa ◽  
T. J. Biden ◽  
P. D. Reynolds ◽  
...  
Keyword(s):  
Insulin Release ◽  
Human Tissue ◽  
Islet Cell ◽  
Cell Function ◽  
Human Islets ◽  
Β Cell ◽  
Pancreatic Islet Cell ◽  
Sigmoidal Curve ◽  
Β Cell Function ◽  
Islet Cell Function

1. β-Cell function in human islets derived from a number of kidney donors was investigated by using various types of islet preparations. 2. With fresh islets, both insulin release and biosynthesis were increased by raising glucose concentrations, although the response was a variable one. 3. In fresh islets, the effects of 5 mmol of glucose/l on release were potentiated by 10 mmol of d-3-hydroxybutyrate/l. 4. Insulin release at 20 mmol of glucose/l was inhibited by adrenaline (0.1 mmol/l), and potentiated by theophylline (10 mmol/l) in the presence of 5 mmol of glucose/l, in islets cultured for 4 days. 5. After culture for 8 days, islets still showed an increase in insulin release and biosynthesis in response to glucose. 6. Pancreas slices derived from fresh human tissue also responded to increasing concentrations of glucose with a sigmoidal curve for insulin release.

Effects of pefloxacin on rat pancreatic islet cell function after 24-hour cold preservation

1997 ◽  
Vol 29 (4) ◽  
pp. 1984-1985
Author(s):  
P. Kwiatkowski ◽  
J. Puc ◽  
M. Rotbart-Fiedor ◽  
S.F. Oluwole ◽  
W. Rowinski ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Islet Cell ◽  
Cell Function ◽  
Pancreatic Islet Cell ◽  
Cold Preservation ◽  
Islet Cell Function ◽  
Rat Pancreatic Islet

Effect of SRY-Related High Mobility Group Box 9 on Extracellular Signal-Regulated Kinase/p38 Signaling Pathway in Glioma

2021 ◽  
Vol 11 (1) ◽  
pp. 171-175
Author(s):  
Tianlong Quan ◽  
Chunhua Zhang ◽  
Xin Song ◽  
Lu Wang
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
High Mobility ◽  
Negative Control ◽  
Glioma Cell Line ◽  
High Mobility Group ◽  
Control Group

As a common malignant tumor in neurosurgery, glioma is characterized as high incidence rate, easy to invade, metastasize and recurrent. It is difficult to treat and has a poor prognosis. The gliomas pathogenesis is complex and has not been fully resolved. Therefore, finding effective molecular targets for glioma is beneficial to improve therapeutic effect. The SRY-related high mobility group box 9 (SOX9) gene involves in mammalian development and is significantly increased in glioma. However, SOX9’s role in gliomas is unclear. The glioma cell line U87 was assigned into control group, scramble group that was transfected with siRNA negative control, and SOX9 siRNA group that was transfected with SOX9 siRNA followed by analysis of SOX9 mRNA and protein level by qPCR and Western blot, cell proliferation by MTT assay, cell apoptosis by Caspase 3 activity assay, cell invasion by Transwell assay, and MMP-9 level by ELISA. SOX9 siRNA transfection significantly downregulated SOX9 mRNA and protein expressions, inhibited U87 cell proliferation, enhanced Caspase 3 activity, suppressed cell invasion of U87, decreased the secretion of MMP-9 in the supernatant, and reduced ERK1/2 and P38 phosphorylation levels (P < 0.05). SOX9 can regulate the progression of glioma by regulating ERK/P38 signaling pathway, promoting cell apoptosis, inhibiting cell proliferation, and restraining cell invasion.

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