scholarly journals Murine macrophages and pancreatic beta cells. Chemotactic properties of insulin and beta-cytostatic action of interleukin 1.

1987 ◽  
Vol 166 (4) ◽  
pp. 1174-1179 ◽  
Author(s):  
E H Leiter
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Beta Cells ◽  
Islet Cells ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Secretory Product ◽  
In Vitro Techniques ◽  
Mouse Pancreatic Islet ◽  
Potential Interactions

This study has used in vitro techniques to investigate the potential interactions between mouse pancreatic islet cells and syngeneic macrophages (M phi). Islets strongly stimulated M phi migration from agarose microdroplets; insulin was the only one of four islet cell hormones tested that was effective individually. Chronic exposure of islet monolayers to recombinant mouse IL-1, an M phi secretory product, was not cytolytic, but inhibited insulin secretion, reduced intracellular insulin content, and produced beta cell-specific degranulation. These effects were unique to IL-1; another monokine, tumor necrosis factor, as well as the lymphokine IL-2, and lymphotoxin were all without effect on insulin secretion or monolayer viability at the concentrations tested. The potential pathological consequences of the chemoattractive action of insulin on M phi, and the inhibitory effect of IL-1 on insulin secretion, are discussed.

scholarly journals Inhibitory effect of somatostatin on insulin secretion is not mediated via the CNS

2015 ◽  
Vol 225 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Astrid C Hauge-Evans ◽  
James Bowe ◽  
Zara J Franklin ◽  
Zoheb Hassan ◽  
Peter M Jones
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Pancreatic Beta Cells ◽  
Plasma Insulin ◽  
Inhibitory Effect ◽  
Isolated Islets ◽  
Glucose Levels ◽  
Blood Glucose Levels

The inhibitory effect of somatostatin (SST) on insulin secretionin vivois attributed to a direct effect on pancreatic beta cells, but this is inconsistent with somein vitroresults in which exogenous SST is ineffective in inhibiting secretion from isolated islets. We therefore investigated whether insulin secretion from the pancreatic islets may partly be regulated by an indirect effect of SST mediated via the CNS. Islet hormone secretion was assessedin vitroby perifusion and static incubations of isolated islets andin vivoby i.v. or i.c.v. administration of the SST analogue BIM23014C with an i.v. glucose challenge to conscious, chronically catheterised rats. Hormone content of samples was assessed by ELISA or RIA and blood glucose levels using a glucose meter. Exogenous SST14/SST28 or BIM23014C did not inhibit the release of insulin from isolated rodent isletsin vitro, whereas peripheral i.v. administration of BIM23014C (7.5 μg) with glucose (1 g/kg) led to decreased plasma insulin content (2.3±0.5 ng insulin/ml versus 4.5±0.5 ng/ml att=5 min,P<0.001) and elevated blood glucose levels compared with those of the controls (29.19±1.3 mmol/l versus 23.5±1.7 mmol/l,P<0.05). In contrast, central i.c.v. injection of BIM23014C (0.75 μg) had no significant effect on either plasma insulin (3.3±0.4 ng/ml,P>0.05) or blood glucose levels (23.5±1.7 mmol/l,P>0.05) although i.v. administration of this dose increased blood glucose concentrations (32.3±0.7 mmol/l,P<0.01). BIM23014C did not measurably alter plasma glucagon, SST, GLP1 or catecholamine levels whether injected i.v. or i.c.v. These results indicate that SST does not suppress insulin secretion by a centrally mediated effect but acts peripherally on islet cells.

scholarly journals Drug reformulation for a neglected disease. The NANOHAT project to develop a safer more effective sleeping sickness drug

2021 ◽  
Vol 15 (4) ◽  
pp. e0009276
Author(s):  
Lisa Sanderson ◽  
Marcelo da Silva ◽  
Gayathri N. Sekhar ◽  
Rachel C. Brown ◽  
Hollie Burrell-Saward ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Structural Characteristics ◽  
Research Programme ◽  
Inhibitory Effect ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Neglected Diseases ◽  
Target Candidate Profile

Background Human African trypanosomiasis (HAT or sleeping sickness) is caused by the parasite Trypanosoma brucei sspp. The disease has two stages, a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system stage where the parasite penetrates the brain, causing death if untreated. Treatment is stage-specific, due to the blood-brain barrier, with less toxic drugs such as pentamidine used to treat stage 1. The objective of our research programme was to develop an intravenous formulation of pentamidine which increases CNS exposure by some 10–100 fold, leading to efficacy against a model of stage 2 HAT. This target candidate profile is in line with drugs for neglected diseases inititative recommendations. Methodology To do this, we evaluated the physicochemical and structural characteristics of formulations of pentamidine with Pluronic micelles (triblock-copolymers of polyethylene-oxide and polypropylene oxide), selected candidates for efficacy and toxicity evaluation in vitro, quantified pentamidine CNS delivery of a sub-set of formulations in vitro and in vivo, and progressed one pentamidine-Pluronic formulation for further evaluation using an in vivo single dose brain penetration study. Principal Findings Screening pentamidine against 40 CNS targets did not reveal any major neurotoxicity concerns, however, pentamidine had a high affinity for the imidazoline2 receptor. The reduction in insulin secretion in MIN6 β-cells by pentamidine may be secondary to pentamidine-mediated activation of β-cell imidazoline receptors and impairment of cell viability. Pluronic F68 (0.01%w/v)-pentamidine formulation had a similar inhibitory effect on insulin secretion as pentamidine alone and an additive trypanocidal effect in vitro. However, all Pluronics tested (P85, P105 and F68) did not significantly enhance brain exposure of pentamidine. Significance These results are relevant to further developing block-copolymers as nanocarriers, improving BBB drug penetration and understanding the side effects of pentamidine.

Dietary fatty acids modify insulin secretion of rat pancreatic islet cells in vitro

2002 ◽  
Vol 25 (5) ◽  
pp. 436-441 ◽  
Author(s):  
F. J. Tinahones ◽  
A. Pareja ◽  
F. J. Soriguer ◽  
J. M. Gómez-Zumaquero ◽  
F. Cardona ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Dietary Fatty Acids ◽  
Pancreatic Islet Cells ◽  
Rat Pancreatic Islet

scholarly journals Determining the Effect of Pterostilbene on Insulin Secretion Using Chemoproteomics

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2885
Author(s):  
Chiara Cassiano ◽  
Daniela Eletto ◽  
Alessandra Tosco ◽  
Raffaele Riccio ◽  
Maria Chiara Monti ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Beta Cells ◽  
Metabolic Disorders ◽  
Therapeutic Potential ◽  
Pharmacological Profile ◽  
Biological Targets ◽  
Cell Assays ◽  
Potential Applications ◽  
Insulin Dependent

Pterostilbene, the 3,5-dimethoxy derivative of resveratrol, is a well-known polyphenolic compound, mainly found in blueberries, grapevines, and Pterocarpus marsupium heartwood, which has recently attracted a great deal of attention due to its wide bio-pharmacological profile. Moreover, pterostilbene is more lipophilic than resveratrol, with a consequently better bioavailability and a more interesting therapeutic potential. In this work, a chemoproteomic approach, based on affinity chromatography, was applied on pterostilbene in the attempt to identify the biological targets responsible for its bioactivity. On this basis, syntaxins, a group of proteins involved in the formation of SNARE complexes mediating vesicles exocytosis, were selected among the most interesting pterostilbene interactors. In vitro and in cell assays gave evidence of the pterostilbene ability to reduce insulin secretion on glucose-stimulated pancreatic beta cells, opening the way to potential applications of pterostilbene as a supplement in the care of insulin-dependent metabolic disorders.

scholarly journals Characterisation of Glucose-Dependent Insulinotropic Polypeptide Receptor Antagonists in Rodent Pancreatic Beta Cells and Mice

2019 ◽  
Vol 12 ◽  
pp. 117955141987545 ◽  
Author(s):  
RA Perry ◽  
SL Craig ◽  
MT Ng ◽  
VA Gault ◽  
PR Flatt ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Beta Cells ◽  
Receptor Activation ◽  
Contributing Factors ◽  
Glucose Lowering ◽  
Incretin Hormone ◽  
Glucose Levels ◽  
First Time ◽  
Gip Receptor

Hypersecretion and alterations in the biological activity of the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), have been postulated as contributing factors in the development of obesity-related diabetes. However, recent studies also point to weight-reducing effects of GIP receptor activation. Therefore, generating precise experimental tools, such as specific and effective GIP receptor (GIPR) antagonists, is of key significance to better understand GIP physiology. Thus, the primary aim of the current study was to uncover improved GIPR antagonists for use in rodent studies, using human and mouse GIP sequences with N- and C-terminal deletions. Initial in vitro studies revealed that the GIPR agonists, human (h) GIP(1-42), hGIP(1-30) and mouse (m) GIP(1-30), stimulated ( P < 0.01 to P < 0.001) insulin secretion from rat BRIN-BD11 cells. Analysis of insulin secretory effects of the N- and C-terminally cleaved GIP peptides, including hGIP(3-30), mGIP(3-30), h(Pro3)GIP(3-30), hGIP(5-30), hGIP(3-42) and hGIP(5-42), revealed that these peptides did not modulate insulin secretion. More pertinently, only hGIP(3-30), mGIP(3-30) and h(Pro3)GIP(3-30) were able to significantly ( P < 0.01 to P < 0.001) inhibit hGIP(1-42)-stimulated insulin secretion. The human-derived GIPR agonist sequences, hGIP(1-42) and hGIP(1-30), reduced ( P < 0.05) glucose levels in mice following conjoint injection with glucose, but mGIP(1-30) was ineffective. None of the N- and C-terminally cleaved GIP peptides affected glucose homeostasis when injected alone with glucose. However, hGIP(5-30) and mGIP(3-30) significantly ( P < 0.05 to P < 0.01) impaired the glucose-lowering action of hGIP(1-42). Further evaluation of these most effective sequences demonstrated that mGIP(3-30), but not hGIP(5-30), effectively prevented GIP-induced elevations of plasma insulin concentrations. These data highlight, for the first time, that mGIP(3-30) represents an effective molecule to inhibit GIPR activity in mice.

scholarly journals Loss-of-Function Mutation of the Galanin Gene Is Associated with Perturbed Islet Function in Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3190-3196 ◽  
Author(s):  
Bo Ahrén ◽  
Giovanni Pacini ◽  
David Wynick ◽  
Nils Wierup ◽  
Frank Sundler
Keyword(s):  
Insulin Secretion ◽  
Islet Cells ◽  
Insulin Response ◽  
Tolerance Test ◽  
Glucose Disposal ◽  
Islet Function ◽  
Loss Of Function ◽  
Euglycemic Hyperinsulinemic Clamp

Abstract The neuropeptide galanin is expressed in sympathetic nerve terminals that surround islet cells and inhibits insulin secretion. To explore its role for islet function, we studied mice with a loss-of-function mutation in the galanin gene [galanin knockout (KO) mice]. Intravenous 2-deoxy-glucose, which activates both the sympathetic and parasympathetic branches of the autonomic nervous system, caused an initial (1–5 min) inhibition of insulin secretion that was impaired in galanin KO mice (P = 0.027), followed by a subsequent stimulation of insulin secretion that was augmented in galanin KO mice (P &lt; 0.01). Similar effects were seen after chemical sympathectomy by 6-hydroxydopamine. In contrast, galanin KO mice had a reduced insulin response to glucose, both in vivo (P &lt; 0.001) and in isolated islets (P &lt; 0.001), and to arginine, both in vivo (P = 0.012) and in vitro (P = 0.018). During an iv glucose tolerance test, galanin KO mice had impaired glucose disposal (P = 0.005) due to a reduced insulin response (P &lt; 0.001) and a reduced insulin-independent glucose elimination (glucose effectiveness; P = 0.040). Insulin sensitivity, as judged by a euglycemic, hyperinsulinemic clamp technique, was slightly increased in galanin KO mice (P = 0.032). We conclude that 1) galanin may contribute to sympathetic influences inhibiting insulin secretion in mice, and 2) galanin KO mice have a reduced glucose-induced insulin secretion.

scholarly journals Alloxan cytotoxicity in vitro. Inhibition of rubidium ion pumping in pancreatic β-cells

1977 ◽  
Vol 162 (1) ◽  
pp. 9-18 ◽  
Author(s):  
L Å Idahl ◽  
Å Lernmark ◽  
J Sehlin ◽  
I B Täljedal
Keyword(s):  
Plasma Membranes ◽  
Islet Cells ◽  
Protective Action ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Nitrophenyl Phosphate ◽  
Cation Pump ◽  
Ion Pumping ◽  
Hydrolysis Of

Exposing micro-dissected pancreatic islets of non-inbred ob/ob mice to 2-5 mM-alloxan for 10 min decreased the ability of the islets to accumulate Rb+. Rb+ accumulation in pieces of exocrine pancreas was unaffected by alloxan. When islets were treated with alloxan in the presence of 2-20 mM-D-glucose, the Rb+-accumulating ability was protected in a dose-dependent manner. The protective action of D-glucose was reproduced with 3-O-methyl-D-glucose but not with L-glucose or D-mannoheptulose; mannoheptulose prevented D-glucose from exerting its protective action. The inhibition of Rb+ accumulation was due to a decreased inward pumping, since alloxan did not affect Rb+ efflux from pre-loaded islets. The inhibitory effect of alloxan had a latency of about 1 min, as revealed by experiments with dispersed islet cells in suspension. Alloxan-treated islets showed only a marginal decrease in ATP and no change in glucose 6-phosphate concentration. Although alloxan slightly decreased the hydrolysis of ATP in a subcellular fraction enriched in plasma membranes, this effect could not be attributed to a ouabain-sensitive adenosine triphosphatase. The plasma membranes exhibited a K+-activated hydrolysis of p-nitrophenyl phosphate; this enzyme activity too was insensitive to alloxan. Glucose may protect the univalent-cation pump by preventing permeation of alloxan via a path coupled to the hexose-transport system. Inhibition of the pump may be fundamental to the induction of alloxan-diabetes.

scholarly journals Ecklonia cavaInhibits Glucose Absorption and Stimulates Insulin Secretion in Streptozotocin-Induced Diabetic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hye Kyung Kim
Keyword(s):  
Insulin Secretion ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Islet Cells ◽  
Glucose Absorption ◽  
Oral Glucose ◽  
Diabetic Mice ◽  
Glucose Transporter 1

Aims of study. Present study investigated the effect ofEcklonia cava(EC) on intestinal glucose uptake and insulin secretion.Materials and methods. Intestinal Na+-dependent glucose uptake (SGU) and Na+-dependent glucose transporter 1 (SGLT1) protein expression was determined using brush border membrane vesicles (BBMVs). Glucose-induced insulin secretion was examined in pancreatic β-islet cells. The antihyperglycemic effects of EC, SGU, and SGLT1 expression were determined in streptozotocin (STZ)-induced diabetic mice.Results. Methanol extract of EC markedly inhibited intestinal SGU of BBMV with the IC50value of 345 μg/mL. SGLT1 protein expression was dose dependently down regulated with EC treatment. Furthermore, insulinotrophic effect of EC extract was observed at high glucose media in isolated pancreatic β-islet cellsin vitro. We next conducted the antihyperglycemic effect of EC in STZ-diabetic mice. EC supplementation markedly suppressed SGU and SGLT1 abundance in BBMV from STZ mice. Furthermore, plasma insulin level was increased by EC treatment in diabetic mice. As a result, EC supplementation improved postprandial glucose regulation, assessed by oral glucose tolerance test, in diabetic mice.Conclusion. These results suggest that EC play a role in controlling dietary glucose absorption at the intestine and insulinotrophic action at the pancreas contributing blood glucose homeostasis in diabetic condition.

scholarly journals Inhibition of murine erythroid colony formation in vitro by interferon gamma and correction by interferon receptor immunoadhesin

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 911-915 ◽  
Author(s):  
RT Jr Means ◽  
SB Krantz ◽  
J Luna ◽  
SA Marsters ◽  
A Ashkenazi
Keyword(s):  
Animal Model ◽  
Interferon Gamma ◽  
Colony Formation ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Ifn Gamma ◽  
Dose Dependent

It has been previously reported that inhibition of human erythroid colony-forming units (CFU-E) in vitro by interleukin-1 (IL-1) is an indirect effect, occurring through the production of interferon gamma (IFN gamma). IFN gamma, in turn, inhibits CFU-E colony formation directly, and its inhibitory effect can be overcome by exposure to high concentrations of erythropoietin (EPO). To develop an in vitro animal model for investigating inhibition of erythropoiesis by IFN gamma, the effects of recombinant murine (rm) IFN gamma on highly purified CFU-E from the spleens of mice infected with the anemia strain of the Friend virus (FVA) were studied. rmIFN gamma inhibited CFU-E colony formation in a dose-dependent manner. This inhibition occurred with large (> or = 8 cell) colonies only; smaller colonies were not affected. The inhibitory effect was corrected to 72% of control by high EPO concentrations of 64 U/mL. Murine CFU-E were then cultured with rmIFN gamma in the presence of a soluble murine IFN gamma receptor fused to the hinge and Fc domains of the human IgG1 heavy chain (mIFN gamma R-IgG). Inhibition of CFU-E colony formation by rmIFN gamma (100 U/mL) was corrected by mIFN gamma R-IgG in a dose-dependent manner, with an approximate IC50 of 0.05 nmol/L, and complete or near complete correction at 0.5 nmol/L. Similarly, a human IFN gamma R-IgG greatly reduced the inhibitory effect of recombinant human IFN gamma on human CFU-E. These experiments provide an in vitro animal model for studying the inhibitory effects of IFN gamma on erythropoiesis and indicate that IFN gamma R-IgG may be a useful agent for reducing the toxicity of IFN gamma in vivo.

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