Insulin Secretion Mechanisms and Glucose Metabolism in Isolated Islets

Ashcroft, S. J. H.; Bassett, J. M.; Randle, P. J.

doi:10.2337/diab.21.2.s538

Cited by 123 publications

(73 citation statements)

References 8 publications

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“…At higher levels, no stimulatory effect is observed as has already been reported [3] (fig.1). Fig.1.…”

Section: Resultssupporting

confidence: 79%

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Direct effects of gold thioglucose on insulin secretion by isolated rat islets of Langerhans

Caterson

Taylor

1979

FEBS Letters

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“…At higher levels, no stimulatory effect is observed as has already been reported [3] (fig.1). Fig.1.…”

Section: Resultssupporting

confidence: 79%

“…It is presumed to act by binding to the glucose receptor cells in the ventromedical hypothalamus. To date there has been little reported on the direct effects of gold thioglucose on isolated islets of Langerhans, though in [3] it was suggested that, at high concentrations it may have no effect on islet function.…”

Section: Introductionmentioning

confidence: 99%

Direct effects of gold thioglucose on insulin secretion by isolated rat islets of Langerhans

Caterson

Taylor

1979

FEBS Letters

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“…A striking correlation between the rates of insulin release and glucose metabolism in non-cultured islets has previously been shown [20,21,22]. After culture of islets in the presence of high or low glucose concentrations, Andersson [2] found increased rates of glucose oxidation in the high-glucose cultured islets, an observation which provides an additional explanation of the greater insulin-releasing effect of glucose in these islets.…”

Section: Discussionmentioning

confidence: 82%

Function of microdissected pancreatic islets cultured in a chemically defined medium. I. Insulin content and release

et al. 1975

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Summary. Microdissected pancreatic islets from non-inbred ob/ ob-mice were cultured for 6 or 7 days in serum-free tissue culture medium 199. The insulin content of the islets decreased 60% during culture in 17 mM or 28 mM glucose and about 70% in the presence of 3.3 mM or 5.6 mM glucose. At the end of a culture period in high glucose, the sum of the insulin in the islet plus that in the culture medium was almost twice as high as the insulin content of fresh islets, indicating an active insulin biosynthesis. The maximal insulin response to glucose after culture in 17 mM or 28 mM glucose was about 40% of that in fresh islets; after culture in 3.3 mM glucose it was 10%. Half-maximal stimulation was observed at a glucose concentration of 5 mM for islets cultured with high glucose as compared to 9 mM for fresh islets. Like glucose, glibenclamide was a more effective insulin stimulator after culture with a high glucose concentration than with a low one. However, leucine-induced insulin release was not affected by the glucose concentration in the preceding culture medium. Whereas potentiation of glucose-stimulated release by arginine or dibutyryl-cAMP was independent of glucose concentration during the culture, theophylline released three times more insulin when the islets had been cultured with high glucose.

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“…The correlation between 45Ca 2+ uptake and insulin release was not as strict as previously reported for rat islets [14, !5]. Thus, tolbutamide, mannose, and L-leucine are clearly less potent than D-glucose in stimulating the release of insulin from normal mouse islets [ 1,2] as well as from the islets of ob/ob-mice [13]. However, these insulin secretagogues appeared equally effective in stimulating the lanthanum-nondisplaceable 45Ca2+ uptake.…”

Section: Discussionmentioning

confidence: 99%

Effects of various modifiers of insulin release on the lanthanum-nondisplaceable45ca2+ uptake by isolated pancreatic islets

et al. 1977

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Summary. The uptake of 45Ca2 + by a lanthanum-nondisplaceable pool in pancreatic islets was studied. Raising the extracellular D-glucose concentration from 3 to 20 mM stimulated the 4SCa2+ uptake in hand-dissected islets of ob/ob-mice as well as in collagenase-isolated islets of ob/ob or normal mice. The effect was dose-dependent in the range of 0-20 mM D-glucose and was seen throughout a wide range of extracellular calcium concentrations (16 gmol -2.56 mmol of Ca 2+ added per litre of medium). The 45Ca2+ uptake was also enhanced by other known insulin secretagogues (D-mannose, L-leucine, tolbutamide) and was uninfluenced by compounds lacking insulinreleasing capacity (3-O-methyl-D-glucose, L-glucose, D-galactose, D-leucine). The stimulatory effect of D-glucose was blocked by inhibitors of glucoseinduced insulin release (D-mannoheptulose, diazoxide, L-adrenaline). The results support the view that the lanthanum-nondisplaceable calcium pool is related to the insulin-releasing mechanism, although the exact nature of this relationship is still unclear.Key words: Calcium uptake, islets of Langerhans, insulin release, ob/ob-mice.The stimulatory effect of D-glucose on 45Ca2+ incorporation into pancreatic islets has been described [9,11,15]. Using lanthanum ions to displace the extracellular calcium and to prevent leakage of the intracellular label after incubation with 45Ca2+, it was shown that the D-glucose-stimulated isotope uptake reflects * On leave from the Institute of Pharmacology and Toxicology, University of Grttingen, D-34 Grttingen, Germany Recipient of a research grant from the Deutsche Forschungsgemeinschaft (Le 348/1) a net flow of calcium into the islet cells [9]. Cell fractionation experiments suggested that the insulin secretory granules participate in the sequestering of the calcium taken up in response to D-glucose [3]. The present study was undertaken to characterize further the lanthanum-nondisplaceable calcium pool by comparing hand-dissected ob/ob-mouse islets with collagenase-isolated islets of normal mice, by defining the dose-response relationships for D-glucose and extracellular calcium, and by studying the influence of several other modifiers of insulin release. Materials and Methods GeneralAdult non-inbred ob/ob-mice or lean mice of normal phenotype were taken from the Ume~ colony and starved overnight. Pancreatic islets were usually microdissected free-hand from ob/ob-mice with the pancreas immersed in basal medium at 2 ~ C. The basal medium in microdissection and subsequent incubations was a salt-balanced tris buffer, the detailed composition of which has been described [9]. In some experiments, islets from ob/ob-mice and lean mice were obtained by collagenase digestion of the pancreas in Hank's solution; these islets, too, were then incubated in tris buffer. All incubations were performed at 37 ~ C in media equilibrated with ambient air. 45Ca2+ UptakeBatches of five islets from ob/ob-mice, or ten from the normal mice, were incubated for 2 h in 200 ~tl of basal medium labelled with 45Ca2...

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Insulin Secretion Mechanisms and Glucose Metabolism in Isolated Islets

Cited by 123 publications

References 8 publications

Direct effects of gold thioglucose on insulin secretion by isolated rat islets of Langerhans

Direct effects of gold thioglucose on insulin secretion by isolated rat islets of Langerhans

Function of microdissected pancreatic islets cultured in a chemically defined medium. I. Insulin content and release

Effects of various modifiers of insulin release on the lanthanum-nondisplaceable45ca2+ uptake by isolated pancreatic islets

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