Evaluation effects of Quercetin on streptozotocin-treated RINm5F pancreatic β-cells in vitro

2021 ◽  
Vol 16 ◽  
Author(s):  
Maryam Mazraesefidi ◽  
Maryam Mohammad Sadeghipour ◽  
Hossein Khorramdelazad ◽  
Mahdi Mahmoodi ◽  
Alireza Khoshdel ◽  
...  
Keyword(s):  
Cell Viability ◽  
Insulin Content ◽  
Β Cells ◽  
Simultaneous Treatment ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
Low Toxicity ◽  
Pre Treatment ◽  
Glucose Stimulated Insulin Secretion

Background and objectives: Quercetin is a naturally occurring phenolic compound abundantly present in plants as a secondary metabolite. The purpose of this study was to investigate the effect of quercetin on improving RINm5F β-insulinemia cell viability, glucose-stimulated insulin secretion (GSIS), and cell insulin content in the presence or absence of streptozotocin (STZ). Methods: This experimental study was conducted on RINm5F β-insulinemia cell line. The cell viability was evaluated by MTT assay. The necrosis was confirmed by flowcytometry and insulin ELISA kit was used to measure the GSIS level and cell insulin content. It should be noted that for testing of cells by 50μM of quercetin, simultaneous treatment and pre-treatment of quercetin were performed in the presence of STZ (20mM). Results: The quercetin was able to improve the viability of RINm5F cells in the presence of STZ and to increase the GSIS level and cell insulin content under STZ and glucotoxic conditions Conclusion: The quercetin seems to have beneficial effects on β-cells, especially the synthesis and secretion of insulin. In addition to the therapeutic effect, given the low toxicity of this flavonoid and the results of this study, the quercetin as a preventive agent may play an important role in maintaining the health of β-cells in people at risk of diabetes.

scholarly journals Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for increasing glucose-stimulated insulin secretion during pregnancy

2007 ◽  
Vol 193 (3) ◽  
pp. 367-381 ◽  
Author(s):  
Anthony J Weinhaus ◽  
Laurence E Stout ◽  
Nicholas V Bhagroo ◽  
T Clark Brelje ◽  
Robert L Sorenson
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Glucose Transporter ◽  
Β Cells ◽  
Glucose Transporter 2 ◽  
Underlying Mechanisms ◽  
Glucose Stimulated Insulin Secretion ◽  
Induced Changes

Glucokinase activity is increased in pancreatic islets during pregnancy and in vitro by prolactin (PRL). The underlying mechanisms that lead to increased glucokinase have not been resolved. Since glucose itself regulates glucokinase activity in β-cells, it was unclear whether the lactogen effects are direct or occur through changes in glucose metabolism. To clarify the roles of glucose metabolism in this process, we examined the interactions between glucose and PRL on glucose metabolism, insulin secretion, and glucokinase expression in insulin 1 (INS-1) cells and rat islets. Although the PRL-induced changes were more pronounced after culture at higher glucose concentrations, an increase in glucose metabolism, insulin secretion, and glucokinase expression occurred even in the absence of glucose. The presence of comparable levels of insulin secretion at similar rates of glucose metabolism from both control and PRL-treated INS-1 cells suggests the PRL-induced increase in glucose metabolism is responsible for the increase in insulin secretion. Similarly, increases in other known PRL responsive genes (e.g. the PRL receptor, glucose transporter-2, and insulin) were also detected after culture without glucose. We show that the upstream glucokinase promoter contains multiple STAT5 binding sequences with increased binding in response to PRL. Corresponding increases in glucokinase mRNA and protein synthesis were also detected. This suggests the PRL-induced increase in glucokinase mRNA and its translation are sufficient to account for the elevated glucokinase activity in β-cells with lactogens. Importantly, the increase in islet glucokinase observed with PRL is in line with that observed in islets during pregnancy.

scholarly journals Natural Phenolic Compounds for the Control of Oxidation, Bacterial Spoilage, and Foodborne Pathogens in Meat

Foods ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 794 ◽  
Author(s):  
Aphrodite I. Kalogianni ◽  
Thomai Lazou ◽  
Ioannis Bossis ◽  
Athanasios I. Gelasakis
Keyword(s):  
Phenolic Compounds ◽  
Foodborne Pathogens ◽  
Current Knowledge ◽  
Antimicrobial Properties ◽  
Meat Industry ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
Antioxidant And Antimicrobial Activity ◽  
Relevant Regulation

Alternative technologies for long-term preservation, quality assurance, and safety of meat are continuously pursued by the food industry to satisfy the demands of modern consumers for nutritious and healthy meat-based products. Naturally occurring phenolic compounds are considered promising substances by the meat industry for their antioxidant and antimicrobial properties, while consumers seem to embrace them for their claimed health benefits. Despite the numerous in vitro and in situ studies demonstrating their beneficial effects against meat oxidation, spoilage, and foodborne pathogens, wide application and commercialization has not been yet achieved. Major obstacles are still the scarcity of legislative framework, the large variety of meat-based products and targeted pathogens, the limited number of case-specific application protocols and the questionable universal efficiency of the applied ones. The objectives of the present review are (i) to summarize the current knowledge about the applications of naturally occurring phenols in meat and meat-based products, emphasizing the mechanisms, determinants, and spectrum of their antioxidant and antimicrobial activity; (ii) to present state-of-the-art technologies utilized for the application of phenolic compounds in meat systems; and (iii) to discuss relevant regulation, limitations, perspectives, and future challenges for their mass industrial use.

Hexosamines regulate sensitivity of glucose-stimulated insulin secretion in β-cells

2006 ◽  
Vol 290 (2) ◽  
pp. E334-E340 ◽  
Author(s):  
Robert C. Cooksey ◽  
Sumitha Pusuluri ◽  
Mark Hazel ◽  
Donald A. McClain
Keyword(s):  
Insulin Secretion ◽  
Glucose Oxidation ◽  
Nutrient Sensing ◽  
Wild Type ◽  
Β Cells ◽  
Enhanced Sensitivity ◽  
Peripheral Insulin Resistance ◽  
Glucose Stimulated Insulin Secretion ◽  
Rate Limiting

Hexosamines serve a nutrient-sensing function through enzymatic O-glycosylation of proteins. We previously characterized transgenic (Tg) mice with overexpression of the rate-limiting enzyme in hexosamine production, glutamine:fructose-6-phosphate amidotransferase, in β-cells. Animals were hyperinsulinemic, resulting in peripheral insulin resistance. Glucose tolerance deteriorated with age, and males developed diabetes. We therefore examined islet function in these mice by perifusion in vitro. Young (2-mo-old) Tg animals had enhanced sensitivity to glucose of insulin secretion. Insulin secretion was maximal at 20 mM and half maximal at 9.9 ± 0.5 mM glucose in Tg islets compared with maximal at 30 mM and half maximal at 13.5 ± 0.7 mM glucose in wild type (WT; P < 0.005). Young Tg animals secreted more insulin in response to 20 mM glucose (Tg, 1,254 ± 311; WT, 425 ± 231 pg·islet−1·35 min−1; P < 0.01). Islets from older (8-mo-old) Tg mice became desensitized to glucose, with half-maximal secretion at 16.1 ± 0.8 mM glucose, compared with 11.8 ± 0.7 mM in WT ( P < 0.05). Older Tg mice secreted less insulin in response to 20 mM glucose (Tg, 2,256 ± 342; WT, 3,493 ± 367 pg·islet−1·35 min−1; P < 0.05). Secretion in response to carbachol was similar in WT and Tg at both ages. Glucose oxidation was blunted in older Tg islets. At 5 mM glucose, islet CO2 production was comparable between Tg and WT. However, WT mice increased islet CO2 production 2.7 ± 0.4-fold in 20 mM glucose, compared with only 1.4 ± 0.1-fold in Tg ( P < 0.02). Results demonstrate that hexosamines are involved in nutrient sensing for insulin secretion, acting at least in part by modulating glucose oxidation pathways. Prolonged excess hexosamine flux results in glucose desensitization and mimics glucose toxicity.

scholarly journals Fructose-1,6-Bisphosphatase Regulates Glucose-Stimulated Insulin Secretion of Mouse Pancreatic β-Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4688-4695 ◽  
Author(s):  
Ye Zhang ◽  
Zhifang Xie ◽  
Guangdi Zhou ◽  
Hai Zhang ◽  
Jian Lu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Specific Inhibitor ◽  
Physiological Role ◽  
Glucose Sensing ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Min6 Cells ◽  
Fructose 1,6 Bisphosphatase ◽  
Glucose Stimulated Insulin Secretion

Pancreatic β-cells can precisely sense glucose stimulation and accordingly adjust their insulin secretion. Fructose-1,6-bisphosphatase (FBPase) is a gluconeogenic enzyme, but its physiological significance in β-cells is not established. Here we determined its physiological role in regulating glucose sensing and insulin secretion of β-cells. Considerable FBPase mRNA was detected in normal mouse islets and β-cell lines, although their protein levels appeared to be quite low. Down-regulation of FBP1 in MIN6 cells by small interfering RNA could enhance the glucose-stimulated insulin secretion (GSIS), whereas FBP1-overexpressing MIN6 cells exhibited decreased GSIS. Inhibition of FBPase activity in islet β-cells by its specific inhibitor MB05032 led to significant increase of their glucose utilization and cellular ATP to ADP ratios and consequently enhanced GSIS in vitro. Pretreatment of mice with the MB05032 prodrug MB06322 could potentiate GSIS in vivo and improve their glucose tolerance. Therefore, FBPase plays an important role in regulating glucose sensing and insulin secretion of β-cells and serves a promising target for diabetes treatment.

Cell-wide analysis of secretory granule dynamics in three dimensions in living pancreatic β-cells: evidence against a role for AMPK-dependent phosphorylation of KLC1 at Ser517/Ser520 in glucose-stimulated insulin granule movement

2010 ◽  
Vol 38 (1) ◽  
pp. 205-208 ◽  
Author(s):  
Angela McDonald ◽  
Sarah Fogarty ◽  
Isabelle Leclerc ◽  
Elaine V. Hill ◽  
D. Grahame Hardie ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glutathione Transferase ◽  
Three Dimensions ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucose Levels ◽  
Insulin Granules ◽  
Elevated Glucose ◽  
Glucose Stimulated Insulin Secretion

Glucose-stimulated insulin secretion from pancreatic β-cells requires the kinesin-1/Kif5B-mediated transport of insulin granules along microtubules. 5′-AMPK (5′-AMP-activated protein kinase) is a heterotrimeric serine/threonine kinase which is activated in β-cells at low glucose concentrations, but inhibited as glucose levels increase. Active AMPK blocks glucose-stimulated insulin secretion and the recruitment of insulin granules to the cell surface, suggesting motor proteins may be targets for this kinase. While both kinesin-1/Kif5B and KLC1 (kinesin light chain-1) contain consensus AMPK phosphorylation sites (Thr693 and Ser520, respectively) only recombinant GST (glutathione transferase)–KLC1 was phosphorylated by purified AMPK in vitro. To test the hypothesis that phosphorylation at this site may modulate kinesin-1-mediated granule movement, we developed an approach to study the dynamics of all the resolvable granules within a cell in three dimensions. This cell-wide approach revealed that the number of longer excursions (>10 μm) increased significantly in response to elevated glucose concentration (30 versus 3 mM) in control MIN6 β-cells. However, similar changes were seen in cells overexpressing wild-type KLC1, phosphomimetic (S517D/S520D) or non-phosphorylatable (S517A/S520A) mutants of KLC1. Thus, changes in the phosphorylation state of KLC1 at Ser517/Ser520 seem unlikely to affect motor function.

Can Functionally Mature Islet β-Cells Be Derived from Pluripotent Stem Cells? – A Step Towards Ready-To-Use β-Cells in Type 1 Diabetes

2020 ◽  
Vol 15 ◽  
Author(s):  
Bishnu K Khand ◽  
Ramesh R Bhonde
Keyword(s):  
Stem Cells ◽  
Type 1 Diabetes ◽  
Pluripotent Stem Cells ◽  
Cell Function ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion

: Pluripotent Stem Cells [PSCs] are emerging as an excellent cellular source for treatment of many degenerative diseases such as diabetes, ischemic heart failure, Alzheimer’s disease. PSC-derived pancreatic islet β-cells appear to be as a promising therapy for type 1 diabetes patients with impaired β-cell function. Several protocols have been developed to derive β-cells from PSCs. However, these protocols produce β-like cells that show low glucose stimulated insulin secretion [GSIS] function and mirror GSIS profile of functionally immature neonatal β-cells. Several studies have documented a positive correlation between the sirtuins [a family of ageing-related proteins] and the GSIS function of adult β-cells. We are of the view that GSIS function of PSC-derived β-like cells could be enhanced by improving the function of sirtuins in them. Studying the sirtuin expression and activation pattern during the β-cell development and inclusion of the sirtuin activator and inhibitor cocktail [specific to a developmental stage] in the present protocols may help us derive functionally mature, ready-to-use β-cells in-vitro making them suitable for transplantation in type 1 diabetes.

scholarly journals Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
M. Olivan ◽  
M. Rigau ◽  
E. Colás ◽  
M. Garcia ◽  
M. Montes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Lipid Lowering ◽  
Concomitant Treatment ◽  
Simultaneous Treatment ◽  
Invasion And Migration ◽  
Beneficial Effects ◽  
Increased Risk ◽  
And Migration

Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812),P<0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155),P=0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939),P<0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effectsin vitroare enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence.

Evidence for paracrine/autocrine regulation of GLP-1-producing cells

2013 ◽  
Vol 305 (10) ◽  
pp. C1041-C1049 ◽  
Author(s):  
Camilla Kappe ◽  
Qimin Zhang ◽  
Jens J. Holst ◽  
Thomas Nyström ◽  
Åke Sjöholm
Keyword(s):  
Cell Viability ◽  
Insulin Signaling ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Novel Drugs ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1), secreted from gut L cells upon nutrient intake, forms the basis for novel drugs against type 2 diabetes (T2D). Secretion of GLP-1 has been suggested to be impaired in T2D and in conditions associated with hyperlipidemia and insulin resistance. Further, recent studies support lipotoxicity of GLP-1-producing cells in vitro. However, little is known about the regulation of L-cell viability/function, the effects of insulin signaling, or the potential effects of stable GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors. We determined effects of insulin as well as possible autocrine action of GLP-1 on viability/apoptosis of GLP-1-secreting cells in the presence/absence of palmitate, while also assessing direct effects on function. The studies were performed using the GLP-1-secreting cell line GLUTag, and palmitate was used to simulate hyperlipidemia. Our results show that palmitate induced production of reactive oxygen species and caspase-3 activity and reduced cell viability are significantly attenuated by preincubation with insulin/exendin-4. The indicated lipoprotective effect of insulin/exendin-4 was not detectable in the presence of the GLP-1 receptor (GLP-1R) antagonist exendin (9–39) and attenuated in response to pharmacological inhibition of exchange protein activated by cAMP (Epac) signaling, while protein kinase A inhibition had no significant effect. Insulin/exendin-4 also significantly stimulate acute and long-term GLP-1 secretion in the presence of glucose, suggesting novel beneficial effects of insulin signaling and GLP-1R activation on glycemia through enhanced mass of GLP-1-producing cells and enhanced GLP-1 secretion. In addition, the effects of insulin indicate that not only is GLP-1 important for insulin secretion but altered insulin signaling may contribute to an altered GLP-1 secretion.

Nano-soldiers Ameliorate Silibinin Delivery: A Review Study

2020 ◽  
Vol 17 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Zahra Ahmadi ◽  
Reza Mohammadinejad ◽  
Tahereh Farkhondeh ◽  
Saeed Samarghandian
Keyword(s):  
Beneficial Effects ◽  
Naturally Occurring ◽  
Bioactive Component ◽  
Daily Diet ◽  
Clinical Disorders ◽  
Health Promoting ◽  
Therapeutic Activities ◽  
Significant Attention

: Flavonoids are a large group of naturally occurring compounds, which are of interest due to their great pharmacological effects and health-promoting impacts. These properties have led to their extensive application in a variety of pathological conditions, particularly cancer. Flavonoids are used in large quantities in a human's daily diet and a high amount of flavonoids are found in the intestine after oral usage. However, flavonoid concentrations in tissue/plasma are low because of their low bioavailability, the leading to the low efficacy of flavonoids in different clinical disorders. For this reason, nanotechnology application for delivering flavonoids to tumor sites has recently received significant attention. Silibinin is a key member of flavonoids and a bioactive component of silymarin, which is widely isolated from Silybum marianum. This plant-derived chemical has a number of valuable biological and therapeutic activities such as antioxidant, anti-inflammatory, neuroprotective, anti-tumor, hepatoprotective, cardioprotective and anti-diabetic. These beneficial effects have been demonstrated in in vivo and in vitro experiments. However, it seems that silibinin has a variety of limitations and poor bioavailability is the most important factor restricting its wide application. Hence, there have been attempts to improve the bioavailability of silibinin and it has been suggested that nano-soldiers are potential candidates for this aim. In the present review, we describe the different drug delivery systems for improving the bioavailability of silibinin.

Acute and long-term effects of metformin on the function and insulin secretory responsiveness of clonal β-cells

2010 ◽  
Vol 391 (12) ◽  
Author(s):  
Joan M. McKiney ◽  
Nigel Irwin ◽  
Peter R. Flatt ◽  
Clifford J. Bailey ◽  
Neville H. McClenaghan
Keyword(s):  
Insulin Secretion ◽  
Cell Viability ◽  
Palmitic Acid ◽  
Insulin Release ◽  
Prolonged Exposure ◽  
Long Term Effects ◽  
Β Cell ◽  
Beneficial Effects ◽  
Intracellular Ca ◽  
Glucose Stimulated Insulin Secretion

Abstract Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic β-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5–50 μm metformin did not alter basal (1.1 mm glucose) or glucose-stimulated (16.7 mm glucose) insulin secretion. However, higher concentrations of metformin (100–1000 μm) increased (1.3–1.5-fold; p<0.001) insulin release at basal glucose concentrations, but had no effect on glucose-stimulated insulin secretion. There were no apparent acute effects of metformin on intracellular Ca2+ concentrations, but metformin enhanced (p<0.05 to p<0.01) the acute insulinotropic actions of GIP and GLP-1. Exposure for 48 h to 200 μm metformin improved aspects of β-cell insulin secretory function, whereas these benefits were lost at 1 mm metformin. Prolonged glucotoxic and lipotoxic conditions impaired β-cell viability and insulin release in response to glucose and to a broad range of insulin secretagogues. Concomitant culture with 200 μm metformin partially reversed many of the adverse effects of prolonged glucotoxic conditions. However, there were no beneficial effects of metformin under prolonged culture with elevated concentrations of palmitic acid. The results suggest that metformin exerts direct effects on β-cell viability, function and survival that could contribute to the use of this agent in the treatment of type 2 diabetes.

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