scholarly journals The stimulation of insulin secretion by d-glyceraldehyde correlates with its rate of oxidation in islet cells

1995 ◽  
Vol 310 (1) ◽  
pp. 215-220 ◽  
Author(s):  
O Alcázar ◽  
E Giné ◽  
Z Qiu-Yue ◽  
J Tamarit-Rodríguez
Keyword(s):  
Insulin Secretion ◽  
Islet Cells ◽  
Aerobic Glycolysis ◽  
Metabolic Effects ◽  
Dependent Manner ◽  
Alternative Routes ◽  
Insulin Responses ◽  
Effect Of Glucose ◽  
Dose Dependent ◽  
Lower Capacity

D-Glyceraldehyde's capacity to mimic the effect of D-glucose on insulin secretion has not yet been sufficiently substantiated. It has been recently proposed, however, that they might act through different mechanisms in insulin-secreting tumoral cells. Therefore, we have performed a dose-related study of both the secretory and metabolic effects of D-glyceraldehyde on islets, which have been compared with those produced by D-glucose. D-Glyceraldehyde's capacity to stimulate secretion was paralleled in a dose-dependent manner by its rate of oxidation to 14CO2. Partial inhibition of D-glyceraldehyde oxidation by beta-iodoacetamide resulted in a proportional decrease in the secretory response. L-Glyceraldehyde, which was apparently very poorly oxidized by islets, did not stimulate secretion. The ratio of the maximum insulin responses D-glyceraldehyde and D-glucose (57%) correlated with the ratio of their respective maximum rates of oxidation (68%). At sub-maximal concentrations there was a potentiation of the secretagogue effects of the hexose by the triose, which was not apparent at a maximum effective dose of glucose. It is concluded that D-glyceraldehyde mimics the secretory effect of glucose because, similarly to the hexose, it is metabolized through islet aerobic glycolysis. The lower potency of D-glyceraldehyde as an insulin secretagogue than D-glucose is determined by the lower capacity of islets to oxidize the triose compared with the hexose. D-Glyceraldehyde, unlike D-glucose, is metabolized in islets to D-lactate. Alternative routes for the metabolism of D-glyceraldehyde might explain some of the secretagogue differences between the triose and the hexose.

Oxotremorine-m potentiation of glucose-induced insulin release from rat islets involves M3 muscarinic receptors

1995 ◽  
Vol 268 (2) ◽  
pp. E336-E342 ◽  
Author(s):  
A. C. Boschero ◽  
M. Szpak-Glasman ◽  
E. M. Carneiro ◽  
S. Bordin ◽  
I. Paul ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Islet Cells ◽  
Insulin Response ◽  
Pcr Amplification ◽  
Dependent Manner ◽  
Muscarinic Receptor Antagonists ◽  
M3 Subtype ◽  
Dose Dependent ◽  
Ach Receptors

cDNAs encoding for M1 and M3 muscarinic acetylcholine (ACh) receptors were detected in rat pancreatic islet cells by polymerase chain reaction (PCR) amplification techniques. A new cholinergic agonist, oxotremorine-m (oxo-m), in the presence of glucose (5.6 mM), produced a dose-dependent potentiation of insulin secretion saturating at approximately 5 microM. This effect was suppressed by the L-type Ca2+ channel blocker nifedipine. Higher doses of oxo-m (50 microM) induced a biphasic insulin response both at low (5.6 mM) or high (16.7 mM) glucose concentrations. In a Ca(2+)-deficient medium containing glucose (5.6 mM), oxo-m evoked only a reduced first phase of insulin secretion. The potentiating effects of oxo-m were inhibited by the muscarinic receptor antagonists 4-diphenylacetoxy-N-methylpiperidine methiodide (M3), hexahydro-sila-difenidol hydrochloride, p-fluoro analogue (M3 > M1 > M2), and pirenzepine (M1) in a dose-dependent manner; half-maximal inhibitory concentration values were approximately 5, 20, and 340 nM, respectively. The PCR results demonstrate the presence of M1 and M3 muscarinic ACh receptors in the islet tissue, and the secretion data strongly suggest that the potentiation of glucose-induced insulin release evoked by oxo-m depends on the activation of a muscarinic M3-subtype receptor present in the beta-cell membrane.

Calcitonin modulation of insulin and glucagon secretion in man

1982 ◽  
Vol 242 (3) ◽  
pp. E206-E213 ◽  
Author(s):  
D. Giugliano ◽  
N. Passariello ◽  
S. Sgambato ◽  
R. Torella ◽  
F. D'Onofrio
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
Glucagon Secretion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Acute Insulin Response ◽  
Insulin Responses ◽  
Effect Of Glucose

These studies were undertaken to evaluate the effect of different doses of calcitonin on insulin and glucagon responses to intravenous glucase loads and to assess the mechanism/s by which calcitonin inhibits insulin secretion in man. In our studies, even the infusion of the 1-U dose of calcitonin was found to inhibit by 45% the acute insulin response to a glucose (20 g) pulse. This effect was associated with a significant decrease in glucose disappearance rates. These negative effects of calcitonin on both insulin secretion and glucose tolerance were dose-related. The inhibition of the acute insulin response to glucose was 65% and up to 90% with the infusion of the 4- and 8-U doses, respectively. The suppressive effect of glucose on glucagon secretion was significantly reduced by calcitonin. The inhibitory effect of calcitonin on insulin responses to glucose (5 g) and glucose tolerance was reversed by both theophylline and calcium. By contrast, infusion of lysine acetylsalicylate to block the synthesis of endogenous prostaglandins did not diminish the inhibitory effect of calcitonin on insulin secretion. These results demonstrate that a) calcitonin inhibits glucose-induced insulin responses and deteriorates glucose tolerance in normal humans in a dose-dependent manner; b) calcitonin reduces the suppressive effect of glucose on glucagon secretion in a dose-related fashion; and c) both theophylline and calcium reverse the inhibitory effect of calcitonin on insulin secretion. It is hypothesized that calcitonin effects on insulin and glucagon release are mediated via a change in calcium redistribution in the islet cells.

scholarly journals GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonathan Snyder ◽  
Atreju I Lackey ◽  
G. Schuyler Brown ◽  
Melisa Diaz ◽  
Tian Yuzhen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Cell Model ◽  
Metabolic Phenotype ◽  
Atp Production ◽  
Pancreatic Islets Of Langerhans ◽  
Cardiac Mitochondrion ◽  
Pre Treatment ◽  
Insulin Responses

AbstractDiabetes is a metabolic syndrome rooted in impaired insulin and/or glucagon secretory responses within the pancreatic islets of Langerhans (islets). Insulin secretion is primarily regulated by two key factors: glucose-mediated ATP production and G-protein coupled receptors (GPCRs) signaling. GPCR kinase 2 (GRK2), a key regulator of GPCRs, is reported to be downregulated in the pancreas of spontaneously obesogenic and diabetogenic mice (ob/ob). Moreover, recent studies have shown that GRK2 non-canonically localizes to the cardiac mitochondrion, where it can contribute to glucose metabolism. Thus, islet GRK2 may impact insulin secretion through either mechanism. Utilizing Min6 cells, a pancreatic ß-cell model, we knocked down GRK2 and measured glucose-mediated intracellular calcium responses and insulin secretion. Silencing of GRK2 attenuated calcium responses, which were rescued by pertussis toxin pre-treatment, suggesting a Gαi/o-dependent mechanism. Pancreatic deletion of GRK2 in mice resulted in glucose intolerance with diminished insulin secretion. These differences were due to diminished insulin release rather than decreased insulin content or gross differences in islet architecture. Furthermore, a high fat diet feeding regimen exacerbated the metabolic phenotype in this model. These results suggest a new role for pancreatic islet GRK2 in glucose-mediated insulin responses that is relevant to type 2 diabetes disease progression.

scholarly journals Chlorotetracycline as a fluorescent Ca2+ probe in pancreatic islet cells.

1978 ◽  
Vol 76 (3) ◽  
pp. 652-674 ◽  
Author(s):  
I B Täljedal
Keyword(s):  
Plasma Membranes ◽  
Islet Cells ◽  
Dependent Manner ◽  
Cell Surfaces ◽  
Noticeable Effect ◽  
Cell Plasma ◽  
Glass Capillaries ◽  
Asymmetrically Distributed ◽  
Dose Dependent ◽  
Dispersed Cells

Pancreatic islets, or suspensions of islet cells, from noninbred ob/ob-mice were incubated with chlorotetracycline and analyzed for Ca2+-dependent fluorescence in a microscope. Unless logarithmically transformed, signals from islets were asymmetrically distributed with unstable variance. Signals from cells pelleted in glass capillaries were more homogeneous and depended linearly on the thickness of the sample. The effect of sample thickness and a significant enhancement of fluorescence by alloxan suggest that beta-cells were involved in producing the signal from whole islets. The signal from dispersed cells was probably diagnostic of Ca2+ in beta-cell plasma membranes because it was suppressed by La3+ and had a spectrum indicative of an apolar micromilieu; fluorescent staining of cell surfaces was directly seen at high magnification. Fluorescence from cells was enhanced by 0.5-10 mM Ca2+ in a dose-dependent manner, whereas less than 0.5 mM Ca2+ saturated the probe alone in methanol. The signal from islets or dispersed cells was suppressed by 5 mM theophylline; that from cells was also suppressed by 0.5 mM 3-isobutyl-1-methylxanthine, 1.2 or 15 mM Mg2+, 3-20 mM D-glucose, and, to a lesser extent, 20 mM 3-O-methyl-D-glucose. D-glucose was more inhibitory in the absence than in the presence of Mg2+, as if Mg2+ and D-glucose influenced the same Ca2+ pool. L-glucose, D-mannopheptulose, or diazoxide had no noticeable effect and 20 mM bicarbonate was stimulatory. The results suggest that microscopy of chlorotetracycline-stained cells can aid in characterizing calcium pools of importance for secretion. Initiation of insulin release may be associated with an increas

Interaction between perchlorate and nifedipine on insulin secretion from mouse pancreastic islets

1993 ◽  
Vol 13 (2) ◽  
pp. 107-117 ◽  
Author(s):  
Gerd Larsson-Nyrén ◽  
Janove Sehlin
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Specific Effect ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Maximum Inhibition ◽  
Second Phases ◽  
Dose Dependent ◽  
Higher Sensitivity

In order to elucidate the mechanisms responsible for the stimulatory effect of perchlorate (ClO4−) on insulin secretion, we have investigated the interaction between this chaotropic anion and the organic calcium antagonist nifedipine. This drug, known as a blocker of L-type calcium channels, was chosen as a tool to test the idea that ClO4− acts on insulin secretion by stimulating the gating of voltage-controlled Ca2+ channels. ClO4− amplified the stimulatory effect of D-glucose on insulin release from perfused pancreas (first and second phases) as well as from isolated islets incubated in static incubations for 60 min. This indicates that ClO4− amplifies physiologically regulated insulin secretion. Nifedipine reduced D-glucose-induced (20 mM) insulin release in a dose-dependent manner with half-maximum effect at about 0.8 μM and apparent maximum effect at 5 μM nifedipine. In the presence of 20 mM D-glucose, the inhibitory effects of 0.5, 1 or 5 μM nifedipine were only slightly, if at all, counteracted by perchlorate. When 12 mM ClO4− and 20 mM D-glucose were combined, calculation of the specific effect of ClO4− revealed that nifedipine produced almost maximum inhibition already at 0.05 μM. Thus, the perchlorate-induced amplification of D-glucose-stimulated insulin release shows higher sensitivity to nifedipine than the D-glucose-effect as such. This supports the hypothesis that perchlorate primarily affects the voltage-sensitive L-type calcium channel in the β-cell.

Does the type of activity “break” from prolonged sitting differentially impact on postprandial blood glucose reductions? An exploratory analysis

2017 ◽  
Vol 42 (8) ◽  
pp. 897-900 ◽  
Author(s):  
Robyn N. Larsen ◽  
Paddy C. Dempsey ◽  
Francis Dillon ◽  
Megan Grace ◽  
Bronwyn A. Kingwell ◽  
...  
Keyword(s):  
Analysis Data ◽  
Postprandial Glucose ◽  
Exploratory Analysis ◽  
Postprandial Blood Glucose ◽  
Moderate Intensity ◽  
Dependent Manner ◽  
Energy Expenditures ◽  
Prolonged Sitting ◽  
Insulin Responses ◽  
Dose Dependent

Frequent breaks in prolonged sitting are associated beneficially with glycaemic control. However, the contribution of energy expenditure to this relationship has not been well characterised. In this exploratory analysis, data from 3 laboratory trials that standardised test meals, cohort characteristics (overweight/obese, sedentary), and break frequency and duration were pooled. Higher energy expenditures of different types of breaks (standing, light- or moderate-intensity walking) were associated with lower postprandial glucose and insulin responses in a dose-dependent manner.

scholarly journals Ingestion of coffee polyphenols increases postprandial release of the active glucagon-like peptide-1 (GLP-1(7–36)) amide in C57BL/6J mice

2015 ◽  
Vol 4 ◽  
Author(s):  
Yoshie Fujii ◽  
Noriko Osaki ◽  
Tadashi Hase ◽  
Akira Shimotoyodome
Keyword(s):  
Insulin Secretion ◽  
Human Subjects ◽  
Coffee Consumption ◽  
Epidemiological Studies ◽  
Diabetes Risk ◽  
Dependent Manner ◽  
Diabetes In Animals ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Dose Dependent

AbstractThe widespread prevalence of diabetes, caused by impaired insulin secretion and insulin resistance, is now a worldwide health problem. Glucagon-like peptide 1 (GLP-1) is a major intestinal hormone that stimulates glucose-induced insulin secretion from β cells. Prolonged activation of the GLP-1 signal has been shown to attenuate diabetes in animals and human subjects. Therefore, GLP-1 secretagogues are attractive targets for the treatment of diabetes. Recent epidemiological studies have reported that an increase in daily coffee consumption lowers diabetes risk. The present study examined the hypothesis that the reduction in diabetes risk associated with coffee consumption may be mediated by the stimulation of GLP-1 release by coffee polyphenol extract (CPE). GLP-1 secretion by human enteroendocrine NCI-H716 cells was augmented in a dose-dependent manner by the addition of CPE, and was compatible with the increase in observed active GLP-1(7–36) amide levels in the portal blood after administration with CPE alone in mice. CPE increased intracellular cyclic AMP (cAMP) levels in a dose-dependent manner, but this was not mediated by G protein-coupled receptor 119 (GPR119). The oral administration of CPE increased diet (starch and glyceryl trioleate)-induced active GLP-1 secretion and decreased glucose-dependent insulinotropic polypeptide release. Although CPE administration did not affect diet-induced insulin secretion, it decreased postprandial hyperglycaemia, which indicates that higher GLP-1 levels after the ingestion of CPE may improve insulin sensitivity. We conclude that dietary coffee polyphenols augment gut-derived active GLP-1 secretion via the cAMP-dependent pathway, which may contribute to the reduced risk of type 2 diabetes associated with daily coffee consumption.

scholarly journals Gypenosides modulate NCX calcium flux, insulin secretion and cytoprotection in BRIN-BD11 pancreatic β-cells

2021 ◽  
Author(s):  
Chinmai Patibandla ◽  
Xinhua Shu ◽  
Angus M Shaw ◽  
Sharron Dolan ◽  
Steven Patterson
Keyword(s):  
Insulin Secretion ◽  
Calcium Flux ◽  
Dependent Manner ◽  
Sodium Calcium Exchanger ◽  
Β Cells ◽  
Antioxidant Genes ◽  
Reverse Mode ◽  
Independent Mechanism ◽  
Antioxidant Gene Expression ◽  
Dose Dependent

AbstractGypenosides are saponins extracted from the plant Gynostemma pentaphyllum, suggested to have antidiabetic and anti-obesity potential. However, its mechanism of action is not fully understood. The present study aimed to investigate the cytoprotective and insulin stimulatory effects of gypenosides using the rat BRIN-BD11 β-cell line. Gypenosides provided a significant cytoprotective effect against palmitate-, peroxide- and cytokine-induced cytotoxicity, with upregulation of antioxidant genes Nrf2, Cat, Sod1, and Gpx1. Acutely, gypenosides enhanced intracellular calcium ([Ca2+]i) and insulin secretion in a dose-dependent manner. The presence of the sodium/calcium exchanger (NCX) reverse mode inhibitor SN-6 blocked the gypenosides mediated increase in [Ca2+]I but not the insulin secretion. These findings indicate that gypenosides may enhance [Ca2+]i by activating the reverse mode of NCX channels and a possible calcium-independent mechanism involved in their insulin secretion. Gypenosides also upregulate the antioxidant gene expression and protect against oxidative stress and lipotoxicity, providing the rationale for their observed antidiabetic actions.

Amylin inhibits glucose-induced insulin secretion in a dose-dependent manner. Study in the perfused rat pancreas

1993 ◽  
Vol 43 (1-2) ◽  
pp. 91-96 ◽  
Author(s):  
Pilar Dégano ◽  
Ramona A. Silvestre ◽  
Mercedes Salas ◽  
Elena Peiró ◽  
José Marco
Keyword(s):  
Insulin Secretion ◽  
Dependent Manner ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Dose Dependent

scholarly journals Protective Effects of Astragaloside IV on Uric Acid-Induced Pancreatic β-Cell Injury through PI3K/AKT Pathway Activation

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Zhenhuan Jiang ◽  
Gang Wang ◽  
Lingling Meng ◽  
Yunzhao Tang ◽  
Min Yang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Insulin Secretion ◽  
Akt Pathway ◽  
Dependent Manner ◽  
Protective Effects ◽  
Pancreatic Β Cell ◽  
Astragaloside Iv ◽  
Β Cell ◽  
Min6 Cells ◽  
Dose Dependent

Background. Elevated uric acid (UA) has been found to damage pancreatic β-cell, promote oxidative stress, and cause insulin resistance in type 2 diabetes (T2D). Astragaloside IV (AS-IV), a major active monomer extracted from Astragalus membranaceus (Fisch.) Bunge. which belongs to TRIB. Galegeae (Br.) Torrey et Gray, Papilionaceae, exhibits various activities in a pathophysiological environment and has been widely employed to treat diseases. However, the effects of AS-IV on UA-induced pancreatic β-cell damage need to be investigated and the associating mechanism needs to be elucidated. This study was designed to determine the protective effects and underlying mechanism of AS-IV on UA-induced pancreatic β-cell dysfunction in T2D. Methods. UA-treated Min6 cells were exposed to AS-IV or wortmannin. Thereafter, the 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide (MTT) assay and flow cytometry were employed to determine the effect of AS-IV on cell proliferation and apoptosis, respectively. Insulin secretion was evaluated using the glucose-stimulated insulin secretion (GSIS) assay. Finally, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to determine the effect of AS-IV on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in UA-treated cells. Results. AS-IV had no cytotoxic effects on Min6 cells. UA significantly suppressed Min6 cell growth, promoted cell apoptosis, and enhanced caspase-3 activity; however, AS-IV abolished these effects in a dose-dependent manner. Further, decreased insulin secretion was found in UA-treated Min6 cells compared to control cells, and the production of insulin was enhanced by AS-IV in a dose-dependent manner. AS-IV significantly increased phosphorylated (p)-AKT expression and the ratio of p-AKT/AKT in Min6 cells exposed to UA. No evident change in AKT mRNA level was found in the different groups. However, the effects of AS-IV on UA-stimulated Min6 cells were reversed by 100 nM wortmannin. Conclusion. Collectively, our data suggest that AS-IV protected pancreatic β-cells from UA-treated dysfunction by activating the PI3K/AKT pathway. Such findings suggest that AS-IV may be an efficient natural agent against T2D.

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