Depolarization-independent net uptake of calcium into clonal insulin-releasing cells exposed to glucose

1983 ◽  
Vol 3 (10) ◽  
pp. 927-937 ◽  
Author(s):  
Erik Gylfe ◽  
Tommy Andersson ◽  
Patrik Rorsman ◽  
Håkan Abrahamsson ◽  
Per Arkhammar ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Insulin Release ◽  
Oxidative Degradation ◽  
Glycolytic Flux ◽  
Glucose Effect ◽  
Clonal Cell Line ◽  
Left Hand ◽  
Net Uptake ◽  
Secretory Pattern ◽  
Net Fluxes

Insulin release, net fluxes of Ca2+, and glucose metabolism were studied in a clonal cell line (RINmSF) established from a transplantable rat islet tumor. The insulin content amounted to only 0.03% of that of the total protein and decreased even further with subsequent passages. The insulin secretion was as high as 10 to 20% of the total hormone content per hour. Insulin release was stimulated by K+ depolarization but not by exposure to glucose. In contrast to this secretory pattern, glucose but not K+ stimulated the net uptake of Ca2+ at micromolar concentrations of the ion. The glucose effect was not mimicked by 20 mM 3-O-methylglucose. It was as pronounced at 1 mM as at 20 mM of the sugar and corresponded to an uptake of 119 fmol cm−2 s−1. Glucose metabolism was typical for tumor cells with a high glycolytic flux and an oxidationtoutilization ratio as low as 0.05–0.15. Maximal oxidative degradation was attained already at l mM. This concentration was also equivalent to the Km for glucose utilization, indicating a substantial left-hand shift of the normal dose-response curve. It is suggested that glucose induces a depolarizationindependent net uptake of Ca2+ by favouring intracellular buffering of the cation.

scholarly journals The stimulus-secretion coupling of glucose-induced insulin release. Does glycolysis control calcium transport in the B-cell?

1976 ◽  
Vol 156 (3) ◽  
pp. 521-525 ◽  
Author(s):  
A Sener ◽  
J Levy ◽  
W J Malaisse
Keyword(s):  
B Cell ◽  
Insulin Release ◽  
Glucose Utilization ◽  
Tight Control ◽  
Glucose Residue ◽  
Experimental Conditions ◽  
Lactate Output ◽  
Net Uptake ◽  
Stimulus Secretion Coupling ◽  
Secretory Pattern

1. The metabolism of glucose and the exchangeable Ca2+ pool were measured in rat pancreatic islets, in order to assess the possible significance of glycolysis in the process of glucose-induced insulin release. 2. At high glucose concentration (16.7 mM), glucose was metabolized at the following rate (pmol of glucose residue/h per islet +/- S.E.M.): 131 +/- 11 for glucose uptake, 129+/-8 for glucose utilization, as judged by the conversion of [5-3H]glucose into 3H2O,60+/-2 for lactate output and 25+/-2 for glucose oxidation. 3. The secretory pattern usually correlated with the metabolic data. For instance, the ability of different sugars (glucose, mannose, fructose, galactose, D-glyceraldehyde) to stimulate lactate output closely paralleled their relative insulinotropic capacity. A disparity between metabolic and secretory responses was, however, encountered in the presence of dibutyryl cyclic AMP and theophylline. 4. Despite this contrasting behaviour, the size of the Ca2+- exchangeable pool (net uptake of 45Ca2+) was invariably proportional to the rate of lactate output under all experimental conditions examined. It is concluded that glycolysis usually exerts a tight control on the rate constant for Ca2+ transport across the B-cell membrane.

Pancreatic Islet Function in ω3 Fatty Acid-Depleted Rats: Glucose Metabolism and Nutrient-Stimulated Insulin Release

Endocrine ◽  
2006 ◽  
Vol 29 (3) ◽  
pp. 457-466 ◽  
Author(s):  
Berrin Oguzhan ◽  
Ying Zhang ◽  
Karim Louchami ◽  
Philippe Courtois ◽  
Laurence Portois ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Insulin Release ◽  
Pancreatic Islet ◽  
Islet Function

scholarly journals EGF receptor stimulation shifts breast cancer cell glucose metabolism toward glycolytic flux through PI3 kinase signaling

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0221294 ◽  
Author(s):  
Kyung-Ho Jung ◽  
Eun Jeong Lee ◽  
Jin Won Park ◽  
Jin Hee Lee ◽  
Seung Hwan Moon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Egf Receptor ◽  
Pi3 Kinase ◽  
Glycolytic Flux ◽  
Kinase Signaling ◽  
Receptor Stimulation ◽  
Cell Glucose

POTENTIATION OF INSULIN RELEASE BY GLUCOSE IN MAN

1975 ◽  
Vol 79 (3) ◽  
pp. 502-510 ◽  
Author(s):  
Erol Cerasi
Keyword(s):  
Glucose Metabolism ◽  
Adenylate Cyclase ◽  
Beta Cell ◽  
Insulin Release ◽  
Insulin Response ◽  
Glucose Infusion ◽  
Insulin Responses

ABSTRACT If two consecutive glucose infusions are administered with 40 min of rest between, the insulin response to the second challenge is markedly potentiated. When the insulin response to the first glucose infusion was suppressed by 65 % with the aid of adrenaline, potentiation of the insulin response to the second infusion was not modified. This suggests that the generation of a state of enhancement in the islet does not necessitate that glucose exerts its insulin releasing action. It is postulated that islet glucose metabolism may be involved in producing the potentiation. Pretreatment of the subjects with a glucose infusion enhanced also the insulin responses to glucagon and to tolbutamide, given intravenously 50 min later. Thus, the potentiation generated by glucose is not restricted to the insulinogenic signal induced by glucose. The eventual role that the beta-cell adenylate cyclase may play in this respect is discussed.

Interaction between glucose metabolism and endogenous insulin release in hypertension

Metabolism ◽  
2002 ◽  
Vol 51 (3) ◽  
pp. 297-303 ◽  
Author(s):  
Silvia Natalucci ◽  
Massimo Boemi ◽  
Daniele Fumelli ◽  
Paolo Fumelli ◽  
Roberto Burattini
Keyword(s):  
Glucose Metabolism ◽  
Insulin Release ◽  
Endogenous Insulin

scholarly journals Abnormal glucose metabolism accompanies failure of glucose to stimulate insulin release from a rat pancreatic cell line (RINm5F)

1983 ◽  
Vol 212 (2) ◽  
pp. 439-443 ◽  
Author(s):  
P A Halban ◽  
G A Praz ◽  
C B Wollheim
Keyword(s):  
Glucose Metabolism ◽  
Cell Line ◽  
Insulin Release ◽  
Glucose Utilization ◽  
Rinm5f Cells ◽  
Pancreatic Cell ◽  
Abnormal Glucose Metabolism ◽  
Isolated Rat Islets ◽  
Stimulate Insulin Release ◽  
Stimulation Of

Glucose metabolism and insulin release were studied in isolated rat islets and in an insulin-producing rat cell-line (RINm5F). Intact islets displayed two components of glucose utilization, with glucose stimulation of insulin release being associated with the high-Km component (reflecting glucokinase-like activity). Glucose failed to stimulate insulin release from RINm5F cells, which only displayed a single low-Km component of glucose utilization. Only low-Km (hexokinase-like) glucose-phosphorylating activity was found for disrupted RINm5F cells. These changes in glucose metabolism may contribute towards the failure of glucose to stimulate insulin release from RINm5F cells.

scholarly journals Glucose Metabolism in Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1460 ◽  
Author(s):  
Liang Yan ◽  
Priyank Raj ◽  
Wantong Yao ◽  
Haoqiang Ying
Keyword(s):  
Pancreatic Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Redox Homeostasis ◽  
Central Carbon Metabolism ◽  
Ductal Adenocarcinoma ◽  
Glycolytic Flux ◽  
Pancreatic Cancer Cells ◽  
Cellular Energetics ◽  
Salvage Pathways

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, with a five-year survival rate of around 5% to 8%. To date, very few available drugs have been successfully used to treat PDAC due to the poor understanding of the tumor-specific features. One of the hallmarks of pancreatic cancer cells is the deregulated cellular energetics characterized by the “Warburg effect”. It has been known for decades that cancer cells have a dramatically increased glycolytic flux even in the presence of oxygen and normal mitochondrial function. Glycolytic flux is the central carbon metabolism process in all cells, which not only produces adenosine triphosphate (ATP) but also provides biomass for anabolic processes that support cell proliferation. Expression levels of glucose transporters and rate-limiting enzymes regulate the rate of glycolytic flux. Intermediates that branch out from glycolysis are responsible for redox homeostasis, glycosylation, and biosynthesis. Beyond enhanced glycolytic flux, pancreatic cancer cells activate nutrient salvage pathways, which includes autophagy and micropinocytosis, from which the generated sugars, amino acids, and fatty acids are used to buffer the stresses induced by nutrient deprivation. Further, PDAC is characterized by extensive metabolic crosstalk between tumor cells and cells in the tumor microenvironment (TME). In this review, we will give an overview on recent progresses made in understanding glucose metabolism-related deregulations in PDAC.

Epinephrine modifications of insulin release and of 86Rb+ or 45Ca2+ fluxes in rat islets

1983 ◽  
Vol 244 (3) ◽  
pp. E245-E252 ◽  
Author(s):  
T. Tamagawa ◽  
J. C. Henquin
Keyword(s):  
Amino Acid ◽  
Insulin Release ◽  
Maximum Effect ◽  
Rat Islets ◽  
High K ◽  
Net Uptake ◽  
Insulinotropic Effect ◽  
Camp Levels ◽  
K Permeability ◽  
86Rb Influx

The effects of epinephrine on insulin release, 86Rb+ fluxes, and 45Ca2+ fluxes were measured in rat islets. In the presence of 10 mM glucose, epinephrine did not affect 86Rb+ influx and slightly increased net uptake. It caused a monophasic inhibition of release and a biphasic decrease in 86Rb+ efflux. A maximum effect was observed with 1 microM epinephrine, but release was more markedly inhibited by lower concentrations of the catecholamine than was the efflux. Epinephrine inhibition of release and efflux was reversed by phentolamine and yohimbine but not by prazosin or propranolol. It was mimicked by norepinephrine and clonidine. The inhibition of 86Rb+ efflux persisted when insulin release was prevented by omission of extracellular calcium. Ouabain or high K+ markedly increased 86Rb+ efflux in the presence of glucose and epinephrine; theophylline and quinine had a similar but smaller effect. None of these agents restored insulin release. Epinephrine abolished the insulinotropic effect of arginine without altering the rise in 86Rb+ efflux triggered by the amino acid. Epinephrine abolished insulin release but inhibited 45Ca2+ efflux only partially during stimulation by glucose or by barium plus theophylline. The results show that epinephrine does not inhibit insulin release by activating the Na pump or by increasing K permeability of the B cell membrane. On the contrary, the inhibition of release is accompanied by a decrease in 86Rb+ efflux. Both result from activation of alpha 2-receptors but are not causally related; they could be due to remodeling of Ca2+ fluxes and/or changes in cAMP levels.

scholarly journals Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic β-cell glucose metabolism and insulin secretion

2006 ◽  
Vol 189 (2) ◽  
pp. 301-310 ◽  
Author(s):  
S Patterson ◽  
P R Flatt ◽  
L Brennan ◽  
P Newsholme ◽  
N H McClenaghan
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Insulin Release ◽  
Cell Function ◽  
Tca Cycle ◽  
Gastric Inhibitory Polypeptide ◽  
Β Cell ◽  
The Metabolic Syndrome ◽  
Cell Glucose

Elevated plasma homocysteine has been reported in individuals with diseases of the metabolic syndrome including vascular disease and insulin resistance. As homocysteine exerts detrimental effects on endothelial and neuronal cells, this study investigated effects of acute homocysteine exposure on β-cell function and insulin secretion using clonal BRIN-BD11 β-cells. Acute insulin release studies in the presence of various test reagents were performed using monolayers of BRIN-BD11 cells and samples assayed by insulin radioimmunoassay. Cellular glucose metabolism was assessed by nuclear magnetic resonance (NMR) analysis following 60-min exposure of BRIN-BD11 cell monolayers to glucose in either the absence or presence of homocysteine. Homocysteine dose-dependently inhibited insulin release at moderate and stimulatory glucose concentrations. This inhibitory effect was reversible at all but the highest concentration of homocysteine. 13C-glucose NMR demonstrated decreased labelling of glutamate from glucose at positions C2, C3 and C4, indicating that the tricarboxylic acid (TCA) cycle-dependent glucose metabolism was reduced in the presence of homocysteine. Homocysteine also dose-dependently inhibited insulinotropic responses to a range of glucose-dependent secretagogues including nutrients (alanine, arginine, 2-ketoisocaproate), hormones (glucagon-like peptide-1 (7–36)amide, gastric inhibitory polypeptide and cholecystokinin-8), neurotransmitter (carbachol), drug (tolbutamide) as well as a depolarising concentration of KCl or elevated Ca2+. Insulin secretion induced by activation of adenylate cyclase and protein kinase C pathways with forskolin and phorbol 12-myristate 13-acetate were also inhibited by homocysteine. These effects were not associated with any adverse action on cellular insulin content or cell viability, and there was no increase in apoptosis/necrosis following exposure to homocysteine. These data indicate that homocysteine impairs insulin secretion through alterations in β-cell glucose metabolism and generation of key stimulus-secretion coupling factors. The participation of homocysteine in possible β-cell demise merits further investigation.

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