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 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.

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.

Sustained exposure of toxically damaged mouse pancreatic islets to high glucose does not increase β-cell dysfunction

1989 ◽  
Vol 123 (1) ◽  
pp. 47-51 ◽  
Author(s):  
D. L. Eizirik ◽  
S. Sandler
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
High Glucose ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Stimulation ◽  
Cell Dysfunction ◽  
Mouse Pancreatic Islets ◽  
Insulin Secretory Response

ABSTRACT The aim of this study was to clarify whether prolonged in-vitro exposure of either normal or damaged β cells to a high glucose environment can be toxic to these cells. For this purpose NMRI mice were injected intravenously with a diabetogenic dose of streptozotocin (SZ; 160 mg/kg) or vehicle alone (controls). Their islets were isolated 15 min after the injection and subsequently maintained in culture for 21 days in the presence of 11·1 or 28 mmol glucose/l. After this period, during acute glucose stimulation, the control islets showed a marked increase in their insulin release in response to a high glucose stimulus. In the SZ-exposed islets there was a decrease in DNA and insulin contents, and a deficient insulin secretory response to glucose. However, in the SZ-damaged islets as well as in the control islets, culture with 28 mmol glucose/l compared with 11·1 mmol glucose/l did not impair islet retrieval after culture, islet DNA content or glucose-induced insulin release. Thus, the degree of damage was similar in the SZ-treated islets cultured at the two concentrations of glucose. These results suggest that glucose is not toxic to normal or damaged mouse pancreatic islets over a prolonged period in tissue culture. Journal of Endocrinology (1989) 123, 47–51

Lack of long-term β-cell glucotoxicity in vitro in pancreatic islets isolated from two mouse strains (C57BL/6J; C57BL/KsJ) with different sensitivities of the β-cells to hyperglycaemia in vivo

1993 ◽  
Vol 136 (2) ◽  
pp. 289-296 ◽  
Author(s):  
C. Svensson ◽  
S. Sandler ◽  
C. Hellerström
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Insulin Biosynthesis ◽  
Mouse Strains ◽  
Β Cells ◽  
Insulin Mrna

ABSTRACT Previous studies have shown that 4 weeks after syngeneic transplantation of a suboptimal number of islets into either C57BL/6J (BL/6J) or C57BL/KsJ (BL/KsJ) diabetic mice there is an impaired insulin secretion by the perfused grafts. After normalization of the blood glucose level with a second islet graft, the BL/6J strain showed restored insulin secretion whilst that of the BL/KsJ strain remained impaired. The aim of the present work was to study the effects of glucose on the in-vitro function of islet β-cells from these two mouse strains, with different sensitivities of their β-cells to glucose in vivo. Isolated pancreatic islets from each strain were kept for 1 week in tissue culture at 5·6, 11, 28 or 56 mmol glucose/l and were subsequently analysed with regard to insulin release, (pro)-insulin and total protein biosynthesis, insulin, DNA and insulin mRNA contents and glucose metabolism. Islets from both strains cultured at 28 or 56 mmol glucose/l showed an increased accumulation of insulin in the culture medium and an enhanced glucose-stimulated insulin release compared with corresponding control islets cultured at 11 mmol glucose/l. After culture at either 5·6 or 56 mmol/l, rates of (pro)insulin biosynthesis were decreased in BL/KsJ islets in short-term incubations at 17 mmol glucose/l, whereas islets cultured at 56 mmol glucose/l showed a marked increase at 1·7 mmol glucose/l. In BL/6J islets, the (pro)insulin biosynthesis rates were similar to those of the BL/KsJ islets with one exception, namely that no decrease was observed at 56 mmol glucose/l. Islets of both strains showed a decreased insulin content after culture with 56 mmol glucose/l. Insulin mRNA content was increased in islets cultured in 28 or 56 mmol glucose/l from both mouse strains. Glucose metabolism showed no differences in the rates of glucose oxidation, however, in islets cultured in 56 mmol glucose/l the utilization of glucose was increased in both BL/6J and BL/KsJ animals. There were no differences in DNA content in islets cultured at different glucose concentrations, suggesting no enhancement of cell death. The present study indicates that, irrespective of genetic background, murine β-cells can adapt to very high glucose concentrations in vitro without any obvious signs of so-called glucotoxicity. Previously observed signs of glucotoxicity in vivo in BL/KsJ islets appear not to be related only to glucose but rather to an additional factor in the diabetic environment. Journal of Endocrinology (1993) 136, 289–296

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 The pentose cycle and insulin release in isolated mouse pancreatic islets during starvation

1975 ◽  
Vol 152 (3) ◽  
pp. 571-576 ◽  
Author(s):  
C J Hedeskov ◽  
K Capito
Keyword(s):  
Glucose Metabolism ◽  
Insulin Release ◽  
Carbon Metabolism ◽  
Glucose Utilization ◽  
Fed State ◽  
Glucose Carbon ◽  
Mouse Pancreatic Islets ◽  
The Absolute ◽  
Total Glucose ◽  
Glucose 6 Phosphate Dehydrogenase

When islets from mice were incubated with 16.7 mM-glucose, previous starvation for 48 h decreased the rate of insulin release by approx. 50% and glucose utilization was decreased by approx. 35%. The maximally extractable activity of glucose 6-phosphate dehydrogenase was diminished by 28% after starvation. The formation of 14CO2 from both [1-14C]glucose was, however, higher than the rate of oxidation of [6-14C]-glucose in islets from both fed and starved mice. The fraction of glucose utilized that was oxidized (specific 14CO2 yield) ranged from one-fifth to one-third and was higher in islets from starved mice with both [1-14C]glucose and [6-14C]glucose as substrate. The contribution of pentose-cycle oxidation to total glucose metabolism was small (3% in the fed state and 4% in the starved state). The absolute rates of glucose carbon metabolism via the pentose-cycle oxidation to total glucose metabolism was small (3% in the fed state and 4% in the starved state). The absolute rates of glucose carbon metabolism via the pentose cycle and the turnover of NADPH in this pathway were identical in islets from fed and starved animals. After incubation at 16.7 mM-glucose for 30 min the contents of glucose (6-phosphate and 6-phosphogluconate were both unchanged by starvation. It is concluded that there is no correlation between the decreased sensitivity of the insulin secretory mechanism during starvation and the metabolism of glucose via the pentose cycle, the islet content of glucose 6-phosphate or 6-phosphogluconate.

scholarly journals Effects of glucose and other modifiers of insulin release on the oxidative metabolism of amino acids in micro-dissected pancreatic islets

1971 ◽  
Vol 123 (4) ◽  
pp. 513-521 ◽  
Author(s):  
B. Hellman ◽  
J. Sehlin ◽  
I.-B. Täljedal
Keyword(s):  
Amino Acids ◽  
Glucose Metabolism ◽  
Cyclic Amp ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Β Cells ◽  
Insulin Secretagogues ◽  
Concentration Changes ◽  
Microdissected Pancreatic Islets ◽  
Oxidation Of Glucose

The oxidation of alanine, arginine, leucine, glucose, and pyruvate was studied in microdissected pancreatic islets of obese–hyperglycaemic mice. The following main observations were made. The oxidation of glucose was enhanced severalfold when its concentration was raised from 3 to 20mm. At the latter concentration the rate was about 65mmol/h per kg dry wt. The oxidation of 17mm-pyruvate amounted to 20mmol/h per kg dry wt. indicating a significant entry of this compound into the β-cells. Leucine oxidation was little affected by concentration changes above 5mm, the rate at 20mm corresponding to about 25% of that obtained with 20mm-glucose. In the absence of glucose, the oxidation of alanine or arginine was barely significant. Glucose stimulated the oxidation of alanine but depressed that of leucine. These effects of glucose were blocked by mannoheptulose or iodoacetamide but were not influenced by adrenaline, diazoxide, dibutyryl 3′:5′-cyclic AMP, or glibenclamide. The rate of alanine oxidation was doubled in the presence of 17mm-pyruvate but was unaffected by citrate or succinate. Succinate depressed the oxidation of leucine. Neither alanine nor leucine significantly affected the oxidation of glucose. It is suggested that the effects of glucose on the oxidation of alanine and leucine were mediated by metabolism of the sugar, and that amino acids do not act as insulin secretagogues by serving as fuels for the β-cells. The results are consistent with the existence of mechanisms auxiliary to glucose metabolism for control of insulin release.

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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