scholarly journals Long-term in vitro exposure to high glucose increases proinsulin-like-molecules release by isolated human islets

1998 ◽  
Vol 158 (2) ◽  
pp. 205-211 ◽  
Author(s):  
F Bertuzzi ◽  
K Saccomanno ◽  
C Socci ◽  
AM Davalli ◽  
MV Taglietti ◽  
...  
Keyword(s):  
High Glucose ◽  
Cell Function ◽  
Human Islets ◽  
Chronic Hyperglycemia ◽  
In Vitro Exposure ◽  
Basal Release ◽  
Human Beta Cell

The aim of this study was to determine the effect of long-term in vitro exposure to high glucose on the release and content of proinsulin and insulin in human islets. After 48 h culture in CMRL medium at 5.5 mM (control islets) and 16.7 mM glucose (experimental islets), islets were perifused and acutely stimulated with 16.7 mM glucose, followed by 3.3 mM glucose. Compared with control islets, experimental islets showed a higher basal release of true insulin and proinsulin-like-molecules (PLM), with no increase of true insulin and PLM release in response to 16.7 mM glucose, and a paradoxical true insulin release in response to 3.3 mM glucose; the PLM/total insulin ratio increased significantly after 16.7 mM glucose. Moreover these islets showed a decreased true insulin content and an increased PLM/total insulin ratio. Quantitative ultrastructural analysis of granules, supported by double gold immunostaining with monoclonal antibodies against proinsulin and insulin, showed an increased proinsulin to insulin ratio in beta-cells from experimental islets. These data support in vitro what was recently shown in vivo, and further confirm that culture in high glucose is a useful tool to mimic the effect of in vivo chronic hyperglycemia on human beta-cell function.

scholarly journals High Glucose Aggravates the Detrimental Effects of Pancreatic Stellate Cells on Beta-Cell Function

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Min Zha ◽  
Wei Xu ◽  
Qing Zhai ◽  
Fengfei Li ◽  
Bijun Chen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
High Glucose ◽  
Cell Function ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
High Concentration ◽  
Gk Rats ◽  
Chop Expression

Background and Aims. We here assess the effects of PSCs onβ-cell function and apoptosisin vivoandin vitro.Materials and Methods.PSCs were transplanted into Wistar and Goto-Kakizaki (GK) rats. Sixteen weeks after transplantation,β-cell function, apoptosis, and islet fibrosis were assessed.In vitrothe effects of PSCs conditioned medium (PSCs-CM) and/or high concentration of glucose on INS-1 cell function was assessed by measuring insulin secretion, INS-1 cell survival, apoptosis, and endoplasmic reticulum stress (ER stress) associated CHOP expression.Results. PSCs transplantation exacerbated the impairedβ-cell function in GK rats, but had no significant effects in Wistar rats.In vitro, PSCs-CM caused impaired INS-1 cell viability and insulin secretion and increased apoptosis, which were more pronounced in the presence of high glucose.Conclusion.Our study demonstrates that PSCs induceβ-cell failurein vitroandin vivo.

scholarly journals Effects of long-term in vitro exposure to phosphodiesterase type-3 inhibitors on follicle and oocyte development

Reproduction ◽  
2005 ◽  
Vol 130 (2) ◽  
pp. 177-186 ◽  
Author(s):  
D Nogueira ◽  
R Cortvrindt ◽  
B Everaerdt ◽  
J Smitz
Keyword(s):  
Somatic Cell ◽  
Cell Function ◽  
Oocyte Growth ◽  
Phosphodiesterase Type ◽  
Type 3 ◽  
The Impact ◽  
Phosphodiesterase Type 3

Germinal vesicle (GV)-stage oocytes retrieved from antral follicles undergo nuclear maturation in vitro, which typically occurs prior to cytoplasmic maturation. Short-term culture with meiotic inhibitors has been applied to arrest oocytes at the GV stage aiming to synchronize nuclear and ooplasmic maturity. However, the results obtained are still far from the in vivo situation. In order to acquire competence, immature oocytes may require meiotic arrest in vitro for a more extended period. The phosphodiesterase type 3-inhibitor (PDE3-I) is a potent meiotic arrester. The effects of a prolonged culture with PDE3-I on oocyte quality prior to and after reversal from the inhibition are not known. This study tested the impact of long-term in vitro exposure of two PDE3-Is, org9935 and cilostamide, on oocytes using a mouse follicle culture model. The results showed that PDE3-I (maximum of 10 μM) during a 12-day culture of follicle-enclosed oocytes did not alter somatic cell proliferation, differentiation or follicle survival. In addition, the steroid production profile was not significantly modified by a 12-day exposure to PDE3-I. The recombinant human chorionic gonadotrophin/recombinant human epidermal growth factor stimulus induced a characteristic normal progesterone peak of luteinization and normal mucification of the cumulus cells, while the enclosed oocyte remained blocked at the GV stage. In vitro maturation of denuded or cumulus-enclosed oocytes derived from org9935- or cilostamide-exposed follicles progressed through meiosis and formed morphologically normal meiotic spindles with chromosomes properly aligned at the equator. In conclusion, long-term culture with PDE3-I was harmless to somatic cell function, differentiation, oocyte growth and maturation. Our results suggested that PDE3-I can be applied when extended oocyte culture is required to improve ooplasmic maturation.

scholarly journals Clinical Trial andIn VitroStudy for the Role of Cartilage and Synovia in Acute Articular Infection

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Elia R. Langenmair ◽  
Eva J. Kubosch ◽  
Gian M. Salzmann ◽  
Samuel Beck ◽  
Hagen Schmal
Keyword(s):  
Clinical Trial ◽  
Cell Function ◽  
Joint Infection ◽  
Synovial Fibroblasts ◽  
Joint Infections ◽  
Anti Inflammatory

Objective. Osteoarthritis is a long-term complication of acute articular infections. However, the roles of cartilage and synovia in this process are not yet fully understood.Methods. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions compared in patients with arthroplasty (n= 8) or with intact joints (n= 67). Cytokines and cell function were also analyzed using a humanin vitromodel of joint infection.Results. Synovial IL-1βlevels were significantly higher in patients with arthroplasty (p= 0.004). Higher IL-1βconcentrations were also found in thein vitromodel without chondrocytes (p< 0.05). The anti-inflammatory cytokines IL-4 and IL-10 were consistently expressedin vivoandin vitro, showing no association with the presence of cartilage or chondrocytes. In contrast, FasL levels increased steadilyin vitro, reaching higher levels without chondrocytes (p< 0.05). Likewise, the viability of synovial fibroblasts (SFB) during infection was higher in the presence of chondrocytes. The cartilage-metabolism markers aggrecan and bFGF were at higher concentrations in intact joints, but also synthesized by SFB.Conclusions. Our data suggest an anti-inflammatory effect of cartilage associated with the SFBs’ increased resistance to infections, which displayed the ability to effectively synthesize cartilage metabolites.The trial is registered with DRKS00003536, MISSinG.

scholarly journals In vivo and in vitro exposure to PCB 153 reduces long-term potentiation.

2000 ◽  
Vol 108 (9) ◽  
pp. 827-831 ◽  
Author(s):  
R J Hussain ◽  
J Gyori ◽  
A P DeCaprio ◽  
D O Carpenter
Keyword(s):  
Long Term Potentiation ◽  
Term Potentiation ◽  
In Vitro Exposure

scholarly journals Cocoa: antioxidant and immunomodulator

2009 ◽  
Vol 101 (7) ◽  
pp. 931-940 ◽  
Author(s):  
Emma Ramiro-Puig ◽  
Margarida Castell
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Cell Signalling ◽  
Antioxidant Properties ◽  
High Dose ◽  
T Helper ◽  
T Helper 1

Cocoa, a product consumed since 600 BC, is now a subject of increasing interest because of its antioxidant properties, which are mainly attributed to the content of flavonoids such as ( − )-epicatechin, catechin and procyanidins. Moreover, recent findings suggest a regulatory effect of cocoa on the immune cells implicated in innate and acquired immunity. Cocoa exerts regulatory activity on the secretion of inflammatory mediators from macrophages and other leucocytesin vitro. In addition, emerging data fromin vivostudies support an immunomodulating effect. Long-term cocoa intake in rats affects both intestinal and systemic immune function. Studies in this line suggest that high-dose cocoa intake in young rats favours the T helper 1 (Th1) response and increases intestinal γδ T lymphocyte count, whereas the antibody-secreting response decreases. The mechanisms involved in this activity are uncertain; nonetheless, because redox-sensitive pathways control immune cell function, the action of cocoa flavonoids on modulating cell signalling and gene expression deserves investigation.

High glucose levels affect spermatogenesis: an in vitro approach

2017 ◽  
Vol 29 (7) ◽  
pp. 1369 ◽  
Author(s):  
Renata S. Tavares ◽  
Joana M. D. Portela ◽  
Maria I. Sousa ◽  
Paula C. Mota ◽  
João Ramalho-Santos ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
High Glucose ◽  
Male Fertility ◽  
Cell Function ◽  
Post Partum ◽  
Cell Number ◽  
Glucose Levels ◽  
Clinical Complications

Besides known factors that may cause male infertility, systemic diseases such as diabetes mellitus may further exacerbate a decline in male fertility. This metabolic disease, clinically characterised by a hyperglycaemic phenotype, has devastating consequences in terms of human health, with reproductive dysfunction being one of the associated clinical complications. Nonetheless, the mechanisms responsible for such alterations are still poorly understood due to the multiplicity of factors involved in the induced pathophysiological changes. With this in mind, we focused on the main mediator of diabetes-associated alterations and performed an in vitro approach to address the effects of high glucose conditions on spermatogenesis, avoiding other confounding in vivo factors. Mouse (5 days post partum) testis fragments were cultured on agar gel stands at a gas–liquid interface with either 5, 25 or 50 mM D-glucose for 3 weeks. Stereological analysis revealed that high D-glucose levels increased Sertoli cell number (P < 0.05) and decreased tubular luminal area (P < 0.01), suggesting an impairment of this somatic cell type. Moreover, higher proliferative activity in a TM4 Sertoli cell line exposed to high D-glucose was found (P < 0.05) without compromising cell viability (P > 0.05), further suggesting altered Sertoli cell maturation. Overall, high D-glucose concentrations may lead to impairment of Sertoli cell function, which, given their significant role in spermatogenic control, may compromise male fertility.

scholarly journals High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Katina D Hulme ◽  
Limin Yan ◽  
Rebecca J Marshall ◽  
Conor J Bloxham ◽  
Kyle R Upton ◽  
...  
Keyword(s):  
Influenza Virus ◽  
High Glucose ◽  
Endothelial Barrier ◽  
Junctional Complex ◽  
Virus Infections ◽  
Glucose Levels ◽  
Severe Influenza

Diabetes mellitus is a known susceptibility factor for severe influenza virus infections. However, the mechanisms that underlie this susceptibility remain incompletely understood. Here, the effects of high glucose levels on influenza severity were investigated using an in vitro model of the pulmonary epithelial-endothelial barrier as well as an in vivo murine model of type II diabetes. In vitro we show that high glucose conditions prior to IAV infection increased virus-induced barrier damage. This was associated with an increased pro-inflammatory response in endothelial cells and the subsequent damage of the epithelial junctional complex. These results were subsequently validated in vivo. This study provides the first evidence that hyperglycaemia may increase influenza severity by damaging the pulmonary epithelial-endothelial barrier and increasing pulmonary oedema. These data suggest that maintaining long-term glucose control in individuals with diabetes is paramount in reducing the morbidity and mortality associated with influenza virus infections.

scholarly journals Neratinib protects pancreatic beta cells in diabetes

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Amin Ardestani ◽  
Sijia Li ◽  
Karthika Annamalai ◽  
Blaz Lupse ◽  
Shirin Geravandi ◽  
...  
Keyword(s):  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Cell Mass ◽  
Human Islets ◽  
Β Cells ◽  
Β Cell

Abstract The loss of functional insulin-producing β-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic β-cell death and dysfunction; its deficiency restores functional β-cells and normoglycemia. The identification of MST1 inhibitors represents a promising approach for a β-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug targeting HER2/EGFR dual kinases, as a potent MST1 inhibitor, which improves β-cell survival under multiple diabetogenic conditions in human islets and INS-1E cells. In a pre-clinical study, neratinib attenuates hyperglycemia and improves β-cell function, survival and β-cell mass in type 1 (streptozotocin) and type 2 (obese Leprdb/db) diabetic mouse models. In summary, neratinib is a previously unrecognized inhibitor of MST1 and represents a potential β-cell-protective drug with proof-of-concept in vitro in human islets and in vivo in rodent models of both type 1 and type 2 diabetes.

Antidiabetic properties of dietary chrysin: a cellular mechanism review

2021 ◽  
Vol 21 ◽  
Author(s):  
Rita Marleta Dewi ◽  
Megawati Megawati ◽  
Lucia Dwi Antika
Keyword(s):  
Animal Studies ◽  
Multiple Organ ◽  
Antidiabetic Activity ◽  
Antidiabetic Agent ◽  
In Vivo Experiments ◽  
Chronic Hyperglycemia ◽  
Organ Failures

: Diabetes mellitus is the most common chronic metabolic disorder and is considered one of the leading causes of morbidity and mortality. The improperly-treated chronic hyperglycemia of diabetes has been related to several long-term complications and multiple organ failures, including nephropathy, which can lead to kidney failure, retinopathy with the potential loss of vision, and cardiovascular symptoms. Current commercially available synthetic glucose-lowering agents have been reported to have several adverse effects. Therefore, the search for alternative remedies such as medicinal plants and their active compounds have attracted attention. Chrysin is an active flavonoid that exists widely in various plants and diets and has been reported to possess pharmacological properties, including antidiabetic activity. Many studies have been conducted to characterize the antidiabetic of chrysin, as well as its potential pathways, in in vitro and in vivo experiments. Chrysin has shown promise as an antidiabetic agent in animal studies, thus, demonstrating its potential to be developed as an antidiabetic drug. This review discussed the antidiabetic action of chrysin and its mechanisms, including targeting different mechanisms such as stimulation of insulin signaling, blockage of endoplasmic reticulum stress and oxidative damage, promotion of skeletal glucose uptake, as well as modulation of apoptosis and autophagy signaling. Additionally, this review would be useful for further studies regarding the mechanism of work of plant derived-compound as a potential antidiabetic agent.

The Long-Term Organ Culture of Tissues from Adult Amphiuma, The Congo Eel

1972 ◽  
Vol 11 (3) ◽  
pp. 799-813
Author(s):  
MARJORIE A. MONNICKENDAM ◽  
M. BALLS
Keyword(s):  
Organ Culture ◽  
Normal Cell ◽  
Cell Function ◽  
Amylase Activity ◽  
In Vitro Study ◽  
Organ Cultures ◽  
Amphibian Species

Fragments of pancreas, liver, spleen, kidney and lung from Amphiuma means, the Congo eel, were maintained in organ culture for up to 35 days in a modified Leibovitz L15 medium. These Amphiuma tissues retained their typical histological features throughout the culture period, surviving better and for longer than tissues from other amphibian species. Liver and spleen survived better in hypotonic or isotonic media (125-230 mosmol/kg) than in hypertonic media (255-305 mosmol/kg). The mitotic incidences of these tissues in vivo were very low, and while there were no significant increases in liver, spleen and lung fragments in vitro, there were large increases in kidney and pancreas fragments. Amylase activity was found in pancreas fragments and in medium from pancreas cultures after 28 days in vitro. Amphiuma organ cultures may be useful in the in vitro study of the control of cell proliferation and cell function while normal cell interactions are maintained.

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