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.

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 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 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.

Glucose transport and phosphorylation in single cardiac myocytes: rate-limiting steps in glucose metabolism

1994 ◽  
Vol 266 (3) ◽  
pp. E326-E333 ◽  
Author(s):  
J. Manchester ◽  
X. Kong ◽  
J. Nerbonne ◽  
O. H. Lowry ◽  
J. C. Lawrence
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transport ◽  
Glucose Concentration ◽  
Adult Rat ◽  
Freeze Dried ◽  
Extracellular Glucose ◽  
Order Of Magnitude ◽  
Rate Limiting ◽  
Intracellular Glucose ◽  
In Cells

Microanalytic methods were used to investigate the regulation of glucose metabolism by insulin in single myocytes isolated from adult rat ventricles. Cultured myocytes were incubated with or without insulin and, with either glucose or 2-deoxyglucose (2-DG), rinsed, and freeze-dried. Individual cells were weighed and levels of 2-DG-6-phosphate (2-DG-6-P) or glucose and glucose 6-phosphate (G-6-P) were determined after enzymatic amplification. In cells incubated with 2-DG, insulin increased the level of 2-DG-6-P by as much as 30-fold, indicative of dramatic activation of glucose transport. In cells incubated with glucose, insulin increased the levels of G-6-P by approximately threefold. Increasing extracellular glucose without insulin also increased G-6-P; however, intracellular glucose concentrations were not increased, indicating that glucose transport is rate limiting in nonstimulated myocytes. In contrast, intracellular glucose concentrations were increased by over an order of magnitude by insulin, reaching 60% of the extracellular glucose concentration. Measurements of glucose and G-6-P in the same insulin-treated cells revealed that accumulation of G-6-P reached a plateau when extracellular glucose was increased > 2 mM. At this point the estimated intracellular glucose concentration was 300 microM, or approximately 10 times the Michaelis constant of hexokinase for glucose. These results indicate that in the presence of insulin and physiological concentrations of glucose, hexokinase is saturated with glucose. Consequently, the rate-limiting step for insulin-stimulated glucose utilization is glucose phosphorylation rather than glucose transport.

Effect of osmolality on glucose metabolism in rabbit kidney cortex and medulla in vitro

1964 ◽  
Vol 207 (2) ◽  
pp. 473-482 ◽  
Author(s):  
James B. Lee ◽  
Vernon K. Vance ◽  
George F. Cahill
Keyword(s):  
Glucose Metabolism ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Lactate Production ◽  
Rabbit Kidney ◽  
Kidney Cortex ◽  
Osmotic Gradient ◽  
Cortical Slice ◽  
Kidney Medulla

Slices of rabbit kidney cortex and medulla were incubated aerobically in media of varying osmotic concentrations. When medium osmolality was reduced below 280–300 mosmoles/kg H2O, by means of decreased sodium chloride and sucrose concentrations, there was an osmotically determined increase in cortical glucose utilization and oxidation, lactate production, and slice weight. Between 280 and 300 mosmoles/kg H2O maximal cortical slice weight loss and inhibition of glucose metabolism occurred, with little further change when medium osmolality was increased to 415 mosmoles/kg H2O. With urea, slice weight and relatively maximal glucose metabolism were maintained at all medium osmotic concentrations between 67 and 548 mosmoles/kg H2O. In contrast, slices of kidney medulla revealed a capacity for extensive glucose oxidation in hyperosmotic media (1,066 mosmoles/kg H2O), while maximal lactate production occurred in hypoosmotic media (67 mosmoles/kg H2O). The findings are interpreted as suggestive of responsiveness of cortical and medullary intermediary metabolism to changes in the "effective" extracellular-to-intracellular osmotic gradient.

scholarly journals Effects in vitro of alloxan on the glucose metabolism of mouse pancreatic B-cells

1979 ◽  
Vol 182 (3) ◽  
pp. 797-802 ◽  
Author(s):  
L. A. Håkan Borg ◽  
Susan J. Eide ◽  
Arne Andersson ◽  
Claes Hellerström
Keyword(s):  
Glucose Metabolism ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Essential Feature ◽  
Inhibitory Effect ◽  
Endogenous Respiration ◽  
Cytotoxic Action ◽  
Dependent Manner ◽  
Isolated Pancreatic Islets

To facilitate detailed studies of the B-cytotoxic action of alloxan we developed a model using isolated pancreatic islets of normal mice. An essential feature of this model is the low temperature employed during exposure to alloxan, which minimizes the degradation of the drug. The islets were incubated with alloxan for 30min at 4°C and subsequently various aspects of their metabolism were studied. The O2 consumption was measured by the Cartesian-diver technique. Islets exposed to 2mm-alloxan and control islets had the same endogenous respiration, whereas the O2 uptake of the alloxan-treated islets was inhibited and that of the control islets stimulated when they were incubated with 28mm-glucose as an exogenous substrate. The islet glucose oxidation was estimated by measurement of the formation of 14CO2 from [U-14C]glucose at 37°C. Compared with the controls, alloxan-treated islets showed a decrease in the glucose-oxidation rate in a dose-dependent manner. Pretreatment of the islets with 28mm-glucose for 30min at 37°C completely protected against this effect, whereas preincubations at glucose concentrations below 16.7mm failed to exert any protective effect. The glucose utilization was estimated as the formation of 3H2O from [5-3H]glucose. Alloxan (2mm) failed to affect islet glucoseutilization rate in the presence of either 2.8 or 28mm-glucose. In contrast, islets exposed to 5 or 10mm-alloxan exhibited lowered glucose utilization. It is concluded that in vitro alloxan has an acute inhibitory effect on the islet glucose metabolism, and that this action can be prevented by previous exposure to a high glucose concentration. The results are consistent with the idea that the B-cytotoxicity of alloxan reflects an interaction with intracellular sites involved in the oxidative metabolism of the B-cell.

scholarly journals Nitric oxide stimulates glucose transport and metabolism in rat skeletal muscle in vitro

1997 ◽  
Vol 322 (1) ◽  
pp. 223-228 ◽  
Author(s):  
Martin E. YOUNG ◽  
George K. RADDA ◽  
Brendan LEIGHTON
Keyword(s):  
Nitric Oxide ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
No Donor ◽  
Lactate Release ◽  
Ly 83583 ◽  
Spermine Nonoate

1. The effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on the rates of glucose transport and utilization and its interaction with insulin were investigated in rat soleus muscle in vitro. SNP stimulated the rate of 2-deoxyglucose transport and insulin-mediated (100 Ɓ-units/ml) rates of both net and [14C]lactate release and the rate of glucose oxidation. The effects of SNP were independent of the concentration-dependent effects of insulin on glucose metabolism. 2. SNP stimulated the insulin-stimulated rates of net and [14C]lactate release and glucose oxidation in a concentration-dependent manner. The rate of [14C]lactate release was also stimulated by another NO donor, (Z)-1-(N-[aminopropyl]-N-[4-(3-aminopropylammonio)butyl]-amino)-diazen-1-ium-1,2-diolate (spermine NONOate). 3. SNP at 5, 10 and 15 mM inhibited the insulin-stimulated rate of glycogen synthesis and this rate was further decreased at 20 and 25 mM SNP. SNP did not affect the rate of glycogen synthesis in the absence of insulin. 4. Haemoglobin, which is a NO scavenger, prevented the stimulation of the rates of [14C]lactate release by SNP or spermine NONOate. 5. The cGMP content was increased maximally (by approx. 80-fold) within 15 min by SNP (15 mM). The cGMP content, raised maximally by SNP, was significantly decreased by the guanylate cyclase inhibitor LY-83583 (10 ƁM). The cGMP analogue 8-bromo-cGMP (100 ƁM) significantly increased the rate of net lactate release. 6. LY-83583 significantly inhibited SNP-stimulated rates of 2-deoxyglucose transport, [14C]lactate release and glucose oxidation. Methylene Blue (another guanylate cyclase inhibitor) also inhibited SNP-stimulated rates of [14C]lactate release. 7. The results suggest that in rat skeletal muscle: (a) nitric oxide (from SNP or spermine NONOate) increases the rate of glucose transport and metabolism, an effect independent of insulin; (b) SNP inhibits insulin-mediated rates of glycogen synthesis; (c) SNP stimulates cGMP formation, which mediates, at least partly, the effects on glucose metabolism; (d) nitric oxide-mediated stimulation of glucose utilization might occur in fibre contraction. The implications of the effects of NO on glucose metabolism are discussed.

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