Interrelationship of islet metabolism, adenosine triphosphate content and insulin release

Ashcroft, S. J. H.; Weerasinghe, L. C. C.; Randle, P. J.

doi:10.1042/bj1320223

Cited by 309 publications

(221 citation statements)

References 17 publications

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“…Our results confirm that D-glyceraldehyde behaves as an initiator of insulin secretion [1] in isolated rat islets: a concentrationdependent study of the secretory response of perifused islets with respect to D-glyceraldehyde has been carried out in the complete absence of glucose. It is shown that a sustained response is already generated at 1 mM D-glyceraldehyde.…”

Section: Discussionsupporting

confidence: 84%

“…D-Glyceraldehyde was recognized as a nutrient secretagogue for insulin more than 20 years ago because it could be metabolized by islet cells and maintain the total content of cellular ATP within a certain concentration range [1]. The capacity of islet cells to metabolize D-glyceraldehyde and to respond with an increased insulin release was later corroborated in several reports [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 96%

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

Garnica

Giné

Qiu-Yue

et al. 1995

Biochemical Journal

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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.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 96%

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

Garnica

Giné

Qiu-Yue

et al. 1995

Biochemical Journal

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“…In comparison with oxygenated islets, anoxic islets exhibited decreased concentrations of glucose-6-phosphate and increased concentrations of fructose-l,6-diphosphate. The concomitant inhibition of glycolytic flux may be due to a low lactate dehydrogenase activity in islets yielding a slow reoxidation of NADH and a slow phosphoglyceraldehyde oxidation under anaerobic conditions.Key words: Anoxia, glucose metabolism, pancreatic islets, Pasteur effect.Stimulation of insulin release by glucose may result from the production of a metabolic signal in the pancreatic B-cells [1][2][3][4]. The understanding of insulin secretion may thus be promoted by insight into the mechanisms that regulate glucose metabolism in these cells.…”

mentioning

confidence: 99%

“…Stimulation of insulin release by glucose may result from the production of a metabolic signal in the pancreatic B-cells [1][2][3][4]. The understanding of insulin secretion may thus be promoted by insight into the mechanisms that regulate glucose metabolism in these cells.…”

mentioning

confidence: 99%

Influence of anoxia on glucose metabolism in pancreatic islets: Lack of correlation between fructose-1,6-diphosphate and apparent glycolytic flux

et al. 1975

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Summary. When equilibrated.with O2-CO 2 (95:5), pancreatic islets of non-inbred ob/ob-mice eXhibited a sigmoidal dependence of 3H20 production on D-(5-aH)-glucose cone, entration; the rate was most sensitive to changes of glucose concentration around 5mM and tended to be maximum above about 15 mM glucose. 3H20 production from more than 5 mM D-(5-3H)-glncose was about twice as fast as the production of 14CO z from equimolar D-(U-14Q) -glucose. Islets equilibrated with N2-CO 2 (95:5) did not exhibit a sigmoidal dose-response curve for 3H20 production, the process being inhibited by anoxia at glucose concentrations above 5mM. Pieces of exoerine pancreas had a slower aerobic 3HzO production than the islets and showed a clear enhancement of the process during anoxia. In comparison with oxygenated islets, anoxic islets exhibited decreased concentrations of glucose-6-phosphate and increased concentrations of fructose-l,6-diphosphate. The concomitant inhibition of glycolytic flux may be due to a low lactate dehydrogenase activity in islets yielding a slow reoxidation of NADH and a slow phosphoglyceraldehyde oxidation under anaerobic conditions.Key words: Anoxia, glucose metabolism, pancreatic islets, Pasteur effect.Stimulation of insulin release by glucose may result from the production of a metabolic signal in the pancreatic B-cells [1][2][3][4]. The understanding of insulin secretion may thus be promoted by insight into the mechanisms that regulate glucose metabolism in these cells. In most other tissues glycolysis is faster during anaerobic than under aerobic conditions. This effect of oxygen, the Pasteur effect, is probably due to the phosphofructokinase being inhibited by ATP and by a fall of ADP [5]. Matschinsky et al. [6] reported the inhibitory influence of ATP on phosphofructokinase in islet extracts. We have investigated the effects of anoxia on glycolysis in the B-cell-rich islets of non-inbred ob/ob-mice by measuring the transmembrane transport of glucose, the islet contents of glucose-6-phosphate and fructose-l,6-diphosphate and the production of 3H20 from D-(5-3H)glucose. Materials and Methods GeneralFresh islets were isolated by free-hand microdissection [7] of pancreatic glands from adult, non-inbred ob/ob-mice from the Ume~ colony; the isolation was performed at 2 ~ with the glands suspended in KrebsRinger bicarbonate buffer equilibrated with O2-CO 2 (95:5). In a few experiments pieces of exocrine pancreas were taken for comparison with the islets.Krebs-Ringer bicarbonate buffer equilibrated with O2-COz (95:5) or N2-CO2 (95:5) was used as basal medium in subsequent incubations at 37 ~ . Isolated islets were subjected to preliminary incubation for 30 min at 37 ~ in the absence or presence (5 raM) of glucose. Incubation was then continued in basal medium supplemented with D-glucose as required; the sugar was added as pure a-D-glucose, but this was done long. before the incubation to allow equlibration of the a and/3 anomers. The detailed incubation procedure depended on the aim of the experiment as follo...

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“…For measurement of ATP, the luciferase assay described by Strehler and Totter [16] was used, with the modifications introduced by Wettermark et al [17] and Ashcroft et al [18]. At the end of the 90 min incubation, 0.03 ml of ice-cold 20% perchloric acid (PCA) was added to the tubes containing 0.6 ml KRB and the islets homogenized by son• for 45 sec.…”

Section: Methodsmentioning

confidence: 99%

Proinsulin synthesis in islets of Langerhans from spiny mice (Acomys cahirinus). comparison with rats and mice

et al. 1976

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Summary. Proinsulin synthesis in response tO different concentrations of glucose has been studied in islets of Langerhans of acomys, rat and mouse. The response to increased glucose was small in acomys when compared with rat or mouse. The time course of the effect of glucose on proinsulin synthesis was also studied in sequential 15 min periods up to 60 min. With 5.5 mM glucose the rate of 3H-leucine incorporation for acomys islets was greater over the periods 15-30, 30-45 and 45-60 min after the addition of glucose to the islets than at 0-15 rain. By contrast rat islets exhibited a greater glucose-induced stimulation between 15-30 and 30-45 min relative to the 0-15 min period and a further increase of the incorporation rate between 45 and 60 min. With 27.5 mM glucose acceleration of incorporation relative to the first 15 min period occurred at 15-30 min; it was then stable up to 60 min for islets both from acomys and from rat. Incorporation into total protein was much greater in acomys than in rat or mouse: thus in 2.75 mM glucose, acomys islets incorporated 5 and 19 times more 3H-leucine into total protein than did islets from rat or mouse respectively. In 27.5 mM glucose the incorporation into total protein of the islets from acomys was 4 and 13 times greater. Islet content of insulin was similar for all three species. No significant changes in ATP content were observed in response to changes in glucose concentration from 2.75 to 27.5 mM. The results demonstrate a decreased responsiveness of proinsulin synthesis to glucose in acomys and are discussed in terms of the known decreased sensitivity of insulin release in this animal. Acomys cahirinus maintained in the Geneva colony exhibit hyperplasia of the islets of Langerhans [1][2][3] and a retarded as well as reduced rate of insulin release in response to glucose challenge by comparison with rats or mice [4][5][6][7]. These differences in the response profile to glucose have been detected in vivo, after either intraperitoneal [4][5] or intravenous [6] glucose injection, and in vitro, using isolated islets [7][8][9]. While acomys islets respond slowly to glucose, the total release of insulin over a two hour period may be comparable to that of rats, at least at higher glucose concentrations [7][8][9], suggesting predominantly early decreased sensitivity to glucose. Indeed, when the early and late release phases were compared in some detail [7][8][9], it was confirmed that the early phase (1-10 rain) of insulin release from acomys islets exhibited both decreased sensitivity to glucose and a decreased release capacity. By contrast, the late phase (20-30 rain) of insulin release from acomys islets exhibited only decreased sensitivity to glucose. As these time/secretion characteristics resemble in some respects observations reported in latent diabetes as well as maturity onset diabetes in man [10][11][12] acomys has attracted attention as a possible "model" of potential usefulness. Because of this and because the insensitivity to glucose might be carried over to the ...

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Interrelationship of islet metabolism, adenosine triphosphate content and insulin release

Cited by 309 publications

References 17 publications

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

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

Influence of anoxia on glucose metabolism in pancreatic islets: Lack of correlation between fructose-1,6-diphosphate and apparent glycolytic flux

Proinsulin synthesis in islets of Langerhans from spiny mice (Acomys cahirinus). comparison with rats and mice

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