Augmentation of glucose induced insulin secretion by pertussis vaccine, phentolamine and benextramine: involvement of mechanisms additional to prevention of the inhibitory actions of catecholamines in rats

1988 ◽  
Vol 118 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Maureen Smith ◽  
Brian L. Furman
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Pertussis Vaccine ◽  
Ex Vivo ◽  
Blocking Agent ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Release In Vitro ◽  
The Relationship

Abstract. Pertussis vaccine, pertussis toxin, and the α-adrenoceptor blocking drug phentolamine augment glucose-induced insulin secretion. The present study was carried out to determine the relationship between this action and the ability of these agents to prevent the inhibitory actions of adrenaline. Pertussis vaccine augmented glucose-induced insulin secretion in rat islets ex vivo and prevented the inhibitory actions of adrenaline and clonidine. Incubation of islets with phentolamine or the irreversible α-adrenoceptor blocking agent benextramine also augmented glucose-induced insulin secretion. However, the α-adrenoceptor blocking drugs idazoxan, yohimbine or phenoxybenzamine, in concentrations that prevented the inhibitory effects of adrenaline and/or clonidine, did not modify glucose-induced insulin release in vitro. Benextramine (1 × 10−5 mol/l) blocked the inhibitory effect of clonidine, whilst having no significant effect on the response to adrenaline. It is concluded that stimulation of insulin secretion by certain α-adrenoceptor blocking drugs can be dissociated from their α-adrenoceptor properties. The ability of pertussis vaccine, phentolamine or benextramine to augment glucose-induced insulin release in vitro is unlikely to be due to the prevention of the inhibitory action of endogenous catecholamines.

Differential effects of microtubule-altering agents on beta-cells during development

1983 ◽  
Vol 245 (4) ◽  
pp. E391-E400
Author(s):  
R. S. Hill ◽  
W. B. Rhoten
Keyword(s):  
Insulin Secretion ◽  
Beta Cells ◽  
Insulin Release ◽  
High Glucose ◽  
Deuterium Oxide ◽  
Inhibitory Effect ◽  
Secretory Response ◽  
Second Phase ◽  
Insulin Secretory Response

The effect of microtubule-altering agents on the insulin secretory response to glucose during the perinatal period was investigated with an in vitro perifusion system. Rat pancreatic mince from day 17 of gestation (D17G) to day 6 postnatally (D6PN) were perifused for 60 min in basal glucose followed by 45 min with high glucose (3.5 mg/ml) or with high glucose plus 10 mM arginine (D17G). The two phases of insulin secretion in response to high glucose developed in an age-dependent and asynchronous manner. The first phase matured between D17G and D18G, and maturation of the second phase occurred subsequently. Vinblastine (VB) (20 or 100 microM) had a differential effect on the insulin secretory response. VB did not inhibit stimulated insulin release at D17G. This absence of an inhibitory effect of VB at D17G could not be explained by the absence of polymerized tubulin because microtubules were present in the control beta-cells and, in addition, VB treatment resulted in the formation of paracrystalline deposits. Subsequently in development, and with isolated islets of the adult, VB inhibited stimulated insulin release. Heavy water (deuterium oxide, D2O) inhibited stimulated insulin secretion at D17G but blocked completely insulin release from the near-term beta-cell. The inhibition of insulin secretion by D2O was rapidly reversed when water replaced D2O in the perifusion media. The results indicate that the maturation of the second phase of insulin secretion coincides with the ability of the microtubule-altering agents to modify the insulin secretory response. One possible explanation for these findings is that at D17G the microtubules are not coupled physicochemically to other molecules or structures necessary for their role in insulin secretion to be expressed fully.

scholarly journals Islet-cell metabolism during insulin release. Effects of glucose, citrate, octanoate, tolbutamide, glucagon and theophylline

1969 ◽  
Vol 115 (2) ◽  
pp. 257-262 ◽  
Author(s):  
W Montague ◽  
K W Taylor
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Islet Cell ◽  
Cell Metabolism ◽  
Inhibitory Effect ◽  
Linear Increase ◽  
Intracellular Concentration ◽  
Extracellular Glucose ◽  
Oxidation Of Glucose

1. Concentrations of glucose 6-phosphate and 6-phosphogluconate were studied in islets of Langerhans isolated from rat pancreas and incubated in the presence of various agents that induce insulin release. 2. In response to rising concentrations of extracellular glucose (2–10mm) there is a linear increase in the intracellular concentration of glucose 6-phosphate, though this is not the case for 6-phosphogluconate, the intracellular concentration of which only increases when the external glucose concentration exceeds 5mm. 3. Tolbutamide, octanoate and citrate, all of which promote insulin secretion from isolated islets, increase the intracellular concentrations of glucose 6-phosphate and 6-phosphogluconate. The results obtained in the presence of octanoate and citrate are compatible with an inhibitory effect of citrate on islet-cell phosphofructokinase. 4. Theophylline and glucagon when incubated with islets in vitro promote insulin release and cause a rise in 6-phosphogluconate concentration and not in that of glucose 6-phosphate. 5. It is suggested that the further metabolism of glucose 6-phosphate through a pathway other than glycolysis is essential for insulin release. One such pathway involves its oxidation to 6-phosphogluconate, which seems to be a necessary accompaniment of insulin secretion due to glucose. The possibility that agents other than glucose promote insulin release by enhancing the oxidation of glucose 6-phosphate through this pathway is discussed.

Insulin secretion in glucosamine-induced hyperglycemia in rats

1965 ◽  
Vol 209 (4) ◽  
pp. 797-802 ◽  
Author(s):  
Julio M. Martin ◽  
Gunta Bambers
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Insulin Injection ◽  
Inhibitory Effect ◽  
Base Line ◽  
Pancreatic Insulin ◽  
Hyperglycemic Effect

The hyperglycemia response produced by the injection of glucosamine in rats has been studied by comparing the effects of equal doses of glucosamine and glucose on blood glucose, circulating insulin, and pancreatic insulin content. The effect of glucosamine and glucose on insulin release from the islets has been studied in vitro by incubating slices of pancreas from normal rats and from rats injected with glucosamine. After glucosamine injection, the blood glucose rose and the circulating insulin decreased. In the glucose-injected group the hyperglycemia was lower and the circulating insulin higher. Insulin output from incubated pancreatic slices of normal rats rose when the glucose concentration in the medium was increased or when tolbutamide was added. A decrease below the base line occurred on the addition of glucosamine or when pancreas slices from glucosamine-injected rats were incubated. Insulin injection decreased the hyperglycemic effect of glucosamine whereas tolbutamide was ineffective. These results suggest that glucosamine exerts an inhibitory effect on insulin release from the pancreas.

scholarly journals α-Glucosidase inhibitors: consistency of in silico docking data with in vitro inhibitory data and inhibitory effect prediction of quercetin derivatives

2019 ◽  
Vol 10 (10) ◽  
pp. 6312-6321 ◽  
Author(s):  
Jianzhong Zhu ◽  
Bin Zhang ◽  
Chinping Tan ◽  
Qiang Huang
Keyword(s):  
In Silico ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Quercetin Derivatives ◽  
In Silico Docking ◽  
Glucosidase Inhibitors ◽  
The Relationship

The relationship between in silico and in vitro experiments regarding the inhibitory effects of polyphenols on α-glucosidase was investigated.

The Hyperglycemic Effect of 1-Deoxy-D-manno-heptulose. Inhibition of Hexokinase, Glucokinase, and Insulin Release in Vitro

1974 ◽  
Vol 52 (11) ◽  
pp. 1078-1081
Author(s):  
B. Leshem ◽  
Y. Sharoni ◽  
E. Dimant
Keyword(s):  
Insulin Release ◽  
Rat Liver ◽  
Inhibitory Effect ◽  
Hydroxyl Group ◽  
Primary Hydroxyl ◽  
Rabbit Pancreas ◽  
Release In Vitro ◽  
Yeast Hexokinase ◽  
Hyperglycemic Effect

Injection of 1-deoxy-D-manno-heptulose (1-DMH, 400 mg, subcutaneously) into rats is associated with a hyperglycemia which reaches a peak after 2 h and is about half that caused by the same dose of D-manno-heptulose (MH). Insulin release from pieces of rabbit pancreas suspended in 15 mM glucose and 20 mM 1-DMH was about 20% of the release in the absence of 1-DMH. Under the same conditions MH caused a complete block of insulin release. Yeast hexokinase was inhibited to the extent of 58% and 68% by 1-DMH and MH (14.3 mM), respectively. 1-DMH is also inferior to MH as an inhibitor of crude rat liver hexokinase and glucokinase. The primary hydroxyl group on carbon-1 of MH is not required for the heptulose to exert its inhibitory effect on hexokinase.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

Plasminogen Depletion during Streptokinase Treatment or Two-Chain Urokinase Incubation Correlates with Decreased Clot Lysability Ex Vivo and In Vitro

1993 ◽  
Vol 70 (06) ◽  
pp. 0998-1004 ◽  
Author(s):  
Páll T Önundarson ◽  
H Magnús Haraldsson ◽  
Lena Bergmann ◽  
Charles W Francis ◽  
Victor J Marder
Keyword(s):  
Myocardial Infarction ◽  
Ex Vivo ◽  
Time Dependent ◽  
State Variables ◽  
Thrombolytic Treatment ◽  
Direct Proportion ◽  
Plasmin Activity ◽  
Plasma Exposure ◽  
The Relationship

SummaryThe relationship between lytic state variables and ex vivo clot lysability was investigated in blood drawn from patients during streptokinase administration for acute myocardial infarction. A lytic state was already evident after 5 min of treatment and after 20 min the plasminogen concentration had decreased to 24%, antiplasmin to 7% and fibrinogen 0.2 g/1. Lysis of radiolabeled retracted clots in the patient plasmas decreased from 37 ± 8% after 5 min to 21 ± 8% at 10 min and was significantly lower (8 ± 9%, p <0.005) in samples drawn at 20, 40 and 80 min. Clot lysability correlated positively with the plasminogen concentration (r = 0.78, p = 0.003), but not with plasmin activity. Suspension of radiolabeled clots in normal plasma pre-exposed to 250 U/ml two-chain urokinase for varying time to induce an in vitro lytic state was also associated with decreasing clot lysability in direct proportion with the duration of prior plasma exposure to urokinase. The decreased lysability correlated with the time-dependent reduction in plasminogen concentration (r = 0.88, p <0.0005). Thus, clot lysability decreases in conjunction with the development of the lytic state and the associated plasminogen depletion. The lytic state may therefore limit reperfusion during thrombolytic treatment.

Monitoring Anticoagulant Therapy by Activated Partial Thromboplastin Time: Hirudin Assessment

1994 ◽  
Vol 72 (05) ◽  
pp. 685-692 ◽  
Author(s):  
Michael T Nurmohamed ◽  
René J Berckmans ◽  
Willy M Morriën-Salomons ◽  
Fenny Berends ◽  
Daan W Hommes ◽  
...  
Keyword(s):  
Whole Blood ◽  
Partial Thromboplastin Time ◽  
Ex Vivo ◽  
Fold Increase ◽  
Heparin Therapy ◽  
Activated Partial Thromboplastin Time ◽  
Recombinant Hirudin ◽  
Interindividual Differences ◽  
The Relationship

SummaryBackground. Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated.Study Objectives. To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers.Results. Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin.Conclusions. All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

scholarly journals Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Vicky Mody ◽  
Joanna Ho ◽  
Savannah Wills ◽  
Ahmed Mawri ◽  
Latasha Lawson ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Inhibitory Effects ◽  
Major Threat ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Computational Molecular Modeling

AbstractEmerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.

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