scholarly journals Glucose metabolism in mouse pancreatic islets

1970 ◽  
Vol 118 (1) ◽  
pp. 143-154 ◽  
Author(s):  
S. J. H. Ashcroft ◽  
C. J. Hedeskov ◽  
P. J. Randle
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Glucose Oxidation ◽  
Phosphate Concentration ◽  
Lactate Output ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
Mouse Pancreatic Islets ◽  
Glucose Phosphorylation

1. Rates of glucose oxidation, lactate output and the intracellular concentration of glucose 6-phosphate were measured in mouse pancreatic islets incubated in vitro. 2. Glucose oxidation rate, measured as the formation of 14CO2 from [U-14C]glucose, was markedly dependent on extracellular glucose concentration. It was especially sensitive to glucose concentrations between 1 and 2mg/ml. Glucose oxidation was inhibited by mannoheptulose and glucosamine but not by phlorrhizin, 2-deoxyglucose or N-acetylglucosamine. Glucose oxidation was slightly stimulated by tolbutamide but was not significantly affected by adrenaline, diazoxide or absence of Ca2+ (all of which may inhibit glucose-stimulated insulin release), by arginine or glucagon (which may stimulate insulin release) or by cycloheximide (which may inhibit insulin synthesis). 3. Rates of lactate formation were dependent on the extracellular glucose concentration and were decreased by glucosamine though not by mannoheptulose; tolbutamide increased the rate of lactate output. 4. Islet glucose 6-phosphate concentration was also markedly dependent on extracellular glucose concentration and was diminished by mannoheptulose or glucosamine; tolbutamide and glucagon were without significant effect. Mannose increased islet fructose 6-phosphate concentration but had little effect on islet glucose 6-phosphate concentration. Fructose increased islet glucose 6-phosphate concentration but to a much smaller extent than did glucose. 5. [1-14C]Mannose and [U-14C]fructose were also oxidized by islets but less rapidly than glucose. Conversion of [1-14C]mannose into [1-14C]glucose 6-phosphate or [1-14C]glucose could not be detected. It is concluded that metabolism of mannose is associated with poor equilibration between fructose 6-phosphate and glucose 6-phosphate. 6. These results are consistent with the idea that glucose utilization in mouse islets may be limited by the rate of glucose phosphorylation, that mannoheptulose and glucosamine may inhibit glucose phosphorylation and that effects of glucose on insulin release may be mediated through metabolism of the sugar.

scholarly journals Long-term effects of glucose on insulin release and glucose oxidation by mouse pancreatic islets maintained in tissue culture

1974 ◽  
Vol 140 (3) ◽  
pp. 377-382 ◽  
Author(s):  
Arne Andersson
Keyword(s):  
Tissue Culture ◽  
B Cells ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
High Glucose ◽  
Glucose Concentration ◽  
Glucose Oxidation ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
Mouse Pancreatic Islets

Rates of glucose oxidation and insulin release in response to a wide range of glucose concentrations were studied in short-term experiments in isolated mouse pancreatic islets maintained in tissue culture for 6 days at either a physiological glucose concentration (6.7mm) or at a high glucose concentration (28mm). The curves relating glucose oxidation or insulin release to the extracellular glucose concentration obtained with islets cultured in 6.7mm-glucose displayed a sigmoid shape similar to that observed for freshly isolated non-cultured islets. By contrast islets that had been cultured in 28mm-glucose showed a linear relationship between the rate of glucose oxidation and the extracellular glucose concentration up to about 8mm-glucose. The maximal oxidative rate was twice that of the non-cultured islets and the glucose concentration associated with the half-maximal rate considerably decreased. In islets cultured at 28mm-glucose there was only a small increase in the insulin release in response to glucose, probably due to a depletion of stored insulin in those B cells that had been cultured in a high-glucose medium. It is concluded that exposure of B cells for 6 days to a glucose concentration comparable with that found in diabetic individuals causes adaptive metabolic alterations rather than degeneration of these cells.

scholarly journals Effect of perchlorate on calcium uptake and insulin secretion in mouse pancreatic islets

1987 ◽  
Vol 248 (1) ◽  
pp. 109-115 ◽  
Author(s):  
J Sehlin
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Oxidation ◽  
Calcium Uptake ◽  
Maximum Effect ◽  
Mouse Pancreatic Islets ◽  
Stimulus Secretion Coupling ◽  
Ca2 Channels

Microdissected beta-cell-rich pancreatic islets of non-inbred ob/ob mice were used in studies of how perchlorate (CIO4-) affects stimulus-secretion coupling in beta-cells. CIO4- at 16 mM potentiated D-glucose-induced insulin release, without inducing secretion at non-stimulatory glucose concentrations. The potentiation mainly applied to the first phase of stimulated insulin release. In the presence of 20 mM-glucose, the half-maximum effect of CIO4- was reached at 5.5 mM and maximum effect at 12 mM of the anion. The potentiation was reversible and inhibitable by D-mannoheptulose (20 mM) or Ca2+ deficiency. CIO4- at 1-8 mM did not affect glucose oxidation. The effects on secretion were paralleled by a potentiation of glucose-induced 45Ca2+ influx during 3 min. K+-induced insulin secretion and 45Ca2+ uptake were potentiated by 8-16 mM-CIO4-. The spontaneous inactivation of K+-induced (20.9 mM-K+) insulin release was delayed by 8 mM-CIO4-. The anion potentiated the 45Ca2+ uptake induced by glibenclamide, which is known to depolarize the beta-cell. Insulin release was not affected by 1-10 mM-trichloroacetate. It is suggested that CIO4- stimulates the beta-cell by affecting the gating of voltage-controlled Ca2+ channels.

Glucose metabolism in rat hypothalamus

1981 ◽  
Vol 98 (4) ◽  
pp. 481-487 ◽  
Author(s):  
Pentti Lautala ◽  
Julio M. Martin
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transport ◽  
Glucose Concentration ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Rat Hypothalamus ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
Phenazine Methosulphate

Abstract. In vitro glucose oxidation and glucose transport in the rat medial (MH) and lateral (LH) hypothalamic areas was measured. Glucose oxidation was calculated from the conversion of [U-14C]glucose to 14C02 and glucose transport from 14C02 produced from [114C]glucose in the presence of phenazine methosulphate and NaF. Increasing glucose in the medium from 1 him to 20 mm enhanced glucose oxidation two-fold in MH and 40% in LH. Addition of insulin, 100 (iU/ml, to the medium decreased glucose oxidation 30% both in MH and LH at both 4 mm and 20 mm glucose. Fasting did not affect glucose oxidation in either of these hypothalamic areas. Glucose transport was not affected by insulin, but was increased significantly when glucose was raised from 0.25 mm to 1.0 mm. Fasting also increased glucose transport in both hypothalamic areas. In conclusion, extracellular glucose concentration seems to be the major regulator of glucose utilization by the rat hypothalamus. Insulin, rather than increasing, seems to decrease glucose oxidation while having no effect on glucose transport.

Glucose-induced pulsatile insulin release from single islets at stable and oscillatory cytoplasmic Ca2+

1998 ◽  
Vol 274 (5) ◽  
pp. E796-E800 ◽  
Author(s):  
Peter Bergsten
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Small Amplitude ◽  
Similar Frequency ◽  
Secretory Rate ◽  
Mouse Pancreatic Islets

The cytoplasmic Ca2+ concentration ([Ca2+]i) and insulin release were measured simultaneously in mouse pancreatic islets cultured overnight. [Ca2+]iwas 105 nM and insulin release 3 pmol ⋅ g−1 ⋅ s−1at 3 mM glucose. An increase to 7 mM glucose reduced [Ca2+]itransiently, whereas insulin release doubled and was pulsatile with a frequency of 0.47 min−1. [Ca2+]i oscillations with similar frequency appeared at 11 mM glucose associated with increased amplitude of the insulin oscillations, raising the secretory rate 10-fold. In the presence of 16 and 20 mM glucose [Ca2+]iwas >300 nM and showed no oscillations apart from two islets, which demonstrated [Ca2+]ioscillations with small amplitude at 16 mM glucose. Insulin release with maintained frequency increased by 46 and 31%, respectively. When the glucose concentration was increased from 3 to 11 mM, [Ca2+]idecreased with a nadir that appeared significantly earlier than when the glucose concentration was raised from 3 to 7 mM. Glucose-induced insulin release from the isolated islet is pulsatile both at stable and oscillatory [Ca2+]i, with changes in secretory rate caused by the sugar also when [Ca2+]iis unchanged.

scholarly journals Long-term effects of a high glucose concentration on cyclic nucleotide phosphodiesterase activity in mouse pancreatic islets maintained in tissue culture

1976 ◽  
Vol 156 (2) ◽  
pp. 461-463 ◽  
Author(s):  
C Berne ◽  
A Andersson
Keyword(s):  
Cyclic Amp ◽  
Pancreatic Islets ◽  
Glucose Concentration ◽  
Phosphodiesterase Activity ◽  
Long Term Effects ◽  
Isolated Pancreatic Islets ◽  
Cyclic Amp Phosphodiesterase ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose

It has been suggested that the stimulatory effect of glucose on insulin release may be mediated by the adenylate cyclase-cyclic AMP phosphodiesterase system. In this study it was found that exposure of isolated pancreatic islets to an elevated extracellular glucose concentration for 1 week in vitro caused an increase of the cyclic AMP phosphodiesterase activity in the islet cells. These and previous data indicate that there is an increased turnover of cyclic AMP in B-cells exposed for a prolonged time to a high extracellular glucose concentration, which also causes an increased turnover rate of insulin.

scholarly journals The pentose cycle and insulin release in mouse pancreatic islets

1972 ◽  
Vol 126 (3) ◽  
pp. 525-532 ◽  
Author(s):  
S. J. H. Ashcroft ◽  
L. C. C. Weerasinghe ◽  
J. M. Bassett ◽  
P. J. Randle
Keyword(s):  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Glucose Utilization ◽  
Fold Increase ◽  
Primary Role ◽  
Mouse Pancreatic Islets ◽  
Oxidation Of Glucose

1. Rates of insulin release, glucose utilization (measured as [3H]water formation from [5-3H]glucose) and glucose oxidation (measured as14CO2 formation from [1-14C]- or [6-14C]-glucose) were determined in mouse pancreatic islets incubated in vitro, and were used to estimate the rate of oxidation of glucose by the pentose cycle pathway under various conditions. Rates of oxidation of [U-14C]ribose and [U-14C]xylitol were also measured. 2. Insulin secretion was stimulated fivefold when the medium glucose concentration was raised from 3.3 to 16.7mm in the absence of caffeine; in the presence of caffeine (5mm) a similar increase in glucose concentration evoked a much larger (30-fold) increase in insulin release. Glucose utilization was also increased severalfold as the intracellular glucose concentration was raised over this range, particularly between 5 and 11mm, but the rate of oxidation of glucose via the pentose cycle was not increased. 3. Glucosamine (20mm) inhibited glucose-stimulated insulin release and glucose utilization but not glucose metabolism via the pentose cycle. No evidence was obtained for any selective effect on the metabolism of glucose via the pentose cycle of tolbutamide, glibenclamide, dibutyryl 3′:5′-cyclic AMP, glucagon, caffeine, theophylline, ouabain, adrenaline, colchicine, mannoheptulose or iodoacetamide. Phenazine methosulphate (5μm) increased pentose-cycle flux but inhibited glucose-stimulated insulin release. 4. No formation of14CO2 from [U-14C]ribose could be detected: [U-14C]xylitol gave rise to small amounts of14CO2. Ribose and xylitol had no effect on the rate of oxidation of glucose; ribitol and xylitol had no effect on the rate of glucose utilization. Ribose, ribitol and xylitol did not stimulate insulin release under conditions in which glucose produced a large stimulation. 5. It is concluded that in normal mouse islets glucose metabolism via the pentose cycle does not play a primary role in insulin-secretory responses.

scholarly journals The metabolism of lipids in mouse pancreatic islets. The biosynthesis of triacylglycerols and phospholipids

1975 ◽  
Vol 152 (3) ◽  
pp. 667-673 ◽  
Author(s):  
C Berne
Keyword(s):  
B Cells ◽  
Pancreatic Islets ◽  
Glucose Concentration ◽  
Secretory Granules ◽  
Phospholipid Biosynthesis ◽  
Glucose Carbon ◽  
Glucose Incorporation ◽  
Extracellular Glucose ◽  
Mouse Pancreatic Islets ◽  
Total Glucose

The rate of incorporation of [U-14C]glucose and [u-14C]palmitate into the lipids of the pancreatic islets of obese-hyperglycaemic mice was examined. The following main observations were made. 1. Both glucose and palmitate were incorporated into lipids in the islets. The fraction of glucose utilized for lipid biosynthesis was calculated to be 3-6% of that oxidized at high and low glucose concentrations, whereas palmitate was about equally divided between oxidation and esterification into lipids. 2. Glucose was primarily incorporated from sn-glycerol 3-phosphate. Of the total glucose carbon incorporated, only 2-4% was recovered as fatty acids. 3. A major portion of both glucose and palmitate was incorporated into phospholipids, whereas 10-30% went into triacylglycerols, depending on the extracellular glucose concentrations. 4. An increase in the glucose concentration from 3.5 to 17 mM caused a twofold increase in the rate of glucose incorporation into triacylglycerols and a fivefold increase in the rate of incorporation into phospholipids. Similar effects were also obtained with normal mouse islets. Palmitate was also preferentially directed into phospholipids by an increased glucose concentration. 5. Islets pre-labelled with radioactive palmitate showed a decrease in triacylglycerol radioactivity when they were subsequently incubated in the absence of exogenous sources of energy. 6. Mannoheptulose inhibited the rate of glucose incorporation into phospholipids, whereas omission of Ca2+ and adrenaline left phospholipid biosynthesis unimpaired. The results suggest that pancreatic B-cells have the capacity to store and utilize energy in the form of triacylglycerols. A stimulation of the B-cells by glucose is followed by an increased rate of phospholipid biosynthesis. However, this does not seem to be directly linked to the release of secretory granules.

scholarly journals Concentration of adenosine 3′:5′-cyclic monophosphate in mouse pancreatic islets measured by a protein-binding radioassay

1973 ◽  
Vol 134 (2) ◽  
pp. 599-605 ◽  
Author(s):  
R. H. Cooper ◽  
S. J. H. Ashcroft ◽  
P. J. Randle
Keyword(s):  
Cyclic Amp ◽  
Protein Binding ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Release Rate ◽  
Glucose Concentration ◽  
Detectable Effect ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets

A protein-binding radioassay for cyclic AMP was modified to detect less than 0.025pmol of the nucleotide. The method was applied to the measurement of cyclic AMP in small numbers of mouse pancreatic islets (as little as 25μg of tissue) by use of barium acetate–H2SO4 for deproteinization. The concentration of cyclic AMP in mouse islets incubated in media containing 3.3 or 20mm-glucose was 0.016pmol/10 islets (approx. 1μm in intracellular water). Glucose concentration (3.3 or 20mm) had no detectable effect on islet concentrations of cyclic AMP with periods of incubation or perifusion ranging from 0.5 to 60min, although insulin release rate was rapidly increased by 20mm-glucose. Caffeine (5mm) or 3-isobutyl-1-methylxanthine (1mm), which are known inhibitors of islet cyclic AMP phosphodiesterase, produced marked and rapid increases in islet cyclic AMP concentration at 3.3 or 20mm-glucose, but only enhanced the insulin release rate at the higher glucose concentration. The role of cyclic AMP in insulin release induced by glucose is discussed.

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