PubMed Health⌕ Search

Biomedical subjects

B Issekutz

Publications and source records attributed to B Issekutz.

At least 19 recordsLinked to original sources
PubMed1987

Increase in the stimulation-induced overflow of glutamate by fluoroacetate, a selective inhibitor of the glial tricarboxylic cycle.

Fluoroacetate is known to be taken up selectively by glia, where after forming fluorocitrate, it inhibits the tricarboxylic acid cycle. Since uptake into glia has a major role in the inactivation of synaptically released glutamate, the effect of fluoroacetate on the overflow of glutamate evoked by electrical field stimulation in slices of rat hippocampus was investigated. In agreement with previous reports, 1 mM fluoroacetate reduced the release and content of glutamine, but increased only slightly the overflow of glutamate induced by stimulation. If, however, 0.5 mM glutamine was added to the superfusion fluid, fluoroacetate nearly tripled the overflow of glutamate evoked by electrical field stimulation. The large glutamate overflow due to field stimulation in the presence of fluoroacetate was fully Ca2+ -dependent. Results confirm the major role of glia in the inactivation of glutamate. The absence of such an uptake may contribute to the in vivo convulsive effect of fluoroacetate.

Animals↗
PubMed1985

Effect of epinephrine on carbohydrate metabolism in exercising dogs.

Well-trained dogs with indwelling arterial and venous catheters ran on a treadmill (15%, 133 m/minute). A mixture of 3-3H: glucose and 14C-glucose (U) or 14C-lactate was infused at a constant rate. Hepatic glucose output (Ra), metabolic clearance rate of glucose (MCR), the percent participation of plasma glucose (G) in lactate production (%L comes from G), peripheral glycogenolysis (GLY) and lactate turnover (RaL) were calculated. Three types of experiments were conducted: (1) Type A, in which Epinephrine (E, 0.5 microgram/kg min) was infused mid-exercise for 75 min; (2) Type B, in which E was infused for three hours and exercise started mid-infusion for 75 min; and (3) Type C in which E and exercise began at the same time. In Type A, E increased G less (+15 mg/dL) than at rest (+50 mg/dL). Unlike at rest, during run E transiently decreased the Ra. The hyperglycemia was entirely due to a marked decrease of MCR. In Type B, E delayed the exercise-induced rise of Ra; and in Type C it delayed the rise of MCR. In all three types E reduced the %L comes from G from the usual 40% to 18% to 20%, and it potentiated the exercise-induced rise of GLY. In Type C, during the first hour, about five times as much lactate was produced (722 mg/kg) as in control runs (149 mg/kg). Beta-blockade abolished all the effects of E on glucose, lactate, MCR, GLY, %L comes from G and RaL. delta Ra and delta MCR rose faster, and they reached values that were approximately twice normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effect of beta-adrenergic blockade on lactate turnover in exercising dogs.

Dogs with indwelling catheters in the jugular vein and in the carotid artery ran on the treadmill (slope: 15%, speed: 133 m/min). Lactate turnover and glucose turnover were measured using [U-14C]lactate and [3-3H]glucose as tracers, according to the primed constant-rate infusion method. In addition, the participation of plasma glucose in lactate production (Ra-L) was measured with [U-14C]glucose. Propranolol was given either (A) before exercise (250 micrograms/kg, iv) or (B) in form of a primed infusion administered to the dog running at a steady rate. Measurements of plasma propranolol concentration showed that in type A experiments plasma propranolol fell in 45 min below the lower limit of the complete beta-blockade. In the first 15 min of work Ra-L rose rapidly; then it fell below that of the control (exercise) values. During steady exercise, the elevated Ra-L was decreased by propranolol infusion close to resting values. beta-Blockade doubled the response of glucose production, utilization, and metabolic clearance rate to exercise. In exercising dogs approximately 40-50% of Ra-L arises from plasma glucose. This value was increased by the blockade to 85-90%. It is concluded that glycogenolysis in the working muscle has a dual control: 1) an intracellular control operating at the beginning of exercise, and 2) a hormonal control involving epinephrine and the beta-adrenergic receptors.

Adrenergic beta-Antagonists↗
PubMed1984

Effect of propranolol in dinitrophenol poisoning.

The effect of the beta-blocker propranolol (PR) in sublethal poisoning with 2, 4,-dinitrophenol (DNP) was studied on carbohydrate kinetics in dogs. Parameters of glucose and lactate turnovers were measured by using a mixture of 3-3H-glucose and 14C-lactate according to the primed constant rate infusion technics. Participation of plasma glucose in lactate production (% L----G) and the rate of peripheral glycogenolysis (GLY) was estimated in experiments using a mixture of 3-3H-glucose and 14C-glucose (U). PR did not interfere with the DNP-induced rise of body temperature (+ 4 degrees C), but completely blocked the rise of lactate production, the lactacidemia and the rise of GLY seen in DNP treated controls. PR significantly increased %L----G, prolonged the DNP induced hyperphosphataemia and it caused a decline of plasma glucose. The effects of the beta-blocker could be overcome by increasing the rate of DNP infusion. It is concluded that in DNP poisoning the beta-adrenergic system plays a major role in the elevated peripheral glycogenolysis and it helps to compensate for the loss of mitochondrial synthesis of ATP by greatly accelerating its cytoplasmic synthesis.

2,4-Dinitrophenol↗
PubMed1981

Effects of glucose infusion on hepatic and muscle glycogenolysis in exercising dogs.

Hepatic glucose production (Ra) and the rate of utilization of nonglucose sources (essentially muscle glycogen) were measured in dogs running on a treadmill (15%, 133 m/min) with indwelling catheters in the jugular vein and carotid artery. A mixture of [3-3H]glucose and [U-14C]glucose was used as tracer according to the principles of the primed constant-rate infusion techniques. Glucose was infused intravenously at a rate (12 mg.kg-1.min-1) about 20% higher than the endogenous glucose Ra in exercising dogs. Glucose infusion started either at the beginning of the run or midexercise. Plasma insulin (IRI), glucagon (IRG), and cAMP levels were measured. Exogenous glucose prevented the usual decline of both plasma glucose and IRI without causing hyperglycemia. Exercise increased the molar ratio of IRG/IRI from 0.7 to 1.4, and glucose infusion lowered it to the resting value. The rise of plasma cAMP was slowed significantly. Both the hepatic glucose Ra and intramuscular glycogenolysis were strongly inhibited and the metabolic clearance rate of glucose was increased by 60-100%. The ratio of the specific activities of [14C]lactate to [14C]glucose indicated that 75-95% of the lactate turnover arose from plasma glucose. The corresponding value in the control group was 40-50%. It is concluded that in prolonged exercise the decline of both plasma glucose and insulin play a major role in preserving glucose homeostasis, by limiting the glucose uptake of the working muscle and by helping to achieve an approximately equal contribution of the liver and the muscle glycogen for the elevated glycolysis.

Animals↗
PubMed1977

Studies on hepatic glucose cycles in normal and methylprednisolone-treated dogs.

In unanesthetized normal and methylprednisolone (MP)-treated dogs the rate of appearance of glucose was measured simultaneously with 2-3H (RA2 = hepatic glucose output), 6-3H (Ra6 = hepatic glucose production), and 14C-glucose (U) (RaC) as tracers (primed constant rate infusion). The substrate ("futile") cycle of glucose (SC: gl in equilibrium gl-6-P) was obtained from Ra2 - Ra6, and Ra6 -RaC gave the recycling (RC) of radiocarbons. In normal dogs SC and RC represented 13% and 11% of Ra6, respectively. MP increased SC almost eightfold without altering RC. Infusion of glucagon (increased breakdown of glycogen, inhibition of glycogen synthetase) or mannoheptulose (inhibition of glucokinase) as well as exercise increased SC. MP greatly potentiated the effect causing SC to rise to 20 times the normal baseline. In both groups there was a direct correlation between Ra6 and SC. Glucose infusion did not alter SC in the controls, but increased it in the MP-treated dogs by suppressing Ra6 more than Ra2. It is suggested that the multifunctional character of gl-6-Pase is at least partly responsible for the glucose substrate cycle, using gl-6-P as one of the phosphate donors: gl-6-P + 3H-gl in equilibrium 3H-gl-6-P+gl. The activity of this enzyme is greatly elevated by the glucocorticoid, and it can be further enhanced by increasing the availability of gl-6-P by raising Ra6.

Animals↗
PubMed1976

Gluconeogenesis from glycerol at rest and during exercise in normal, diabetic, and methylprednisolone-treated dogs.

Glucose turnover, glycerol turnover, and the rate of incorporation of glycerol carbon into glucose were measured with the tracer technique (primed constant rate infusion) using 2-3H-glucose and 14C-glycerol, at rest and during exercise (treadmill run) in normal (N), alloxan-diabetic (D), and methylprednisolone treated diabetic (MPD) dogs. At rest only 2%-3% of the hepatic glucose output arose from glycerol. Exercise increased gluconeogenesis about ninefold in N dogs and about fourfold in D and MPD animals, yet less than 9% of the elevated glucose turnover was derived from glycerol. There was a direct linear correlation between the rates of glycerol turnover and gluconeogenesis from glycerol at rest and during exercise in all three groups. The slope constants were however significantly different: 0.45, 0.51, and 0.67 for N, D, and MPD dogs, respectively. In vivo the major factor controlling the rate of gluconeogenesis from glycerol seems to be the glycerol supply on which the specific effects of insulin deficiency and glucocorticoid treatment are superimposed. They appear to be of minor importance. A comparison of the glucose turnover measured by 2-3H-glucose with that measured by 6-3H-glucose showed that the activity of the glucose in equilibrium glucose-6-P cycle was threefold higher in D dogs and elevated by 15-fold in MPD animals.

Animals↗
PubMed1976

Lactate metabolism in resting and exercising dogs.

The effect of treadmill run on the turnover rates of glucose ([2-3H]glucose) and lactate ([U-14C]lactate), on the rates of oxidation (ROX) of lactate, and its conversion to glucose (L LEADS TO G) were measured with the primed constant-infusion technique. Comparable lactate turnover rates were obtained at rest by infusing epinephrine, or Na-L(+)-lactate with or without norepinephrine. With increasing lactate levels (L) the rate of disappearance (RdL), ROX, and L leads to G increase in a linear manner. At the same lactate level, RdL, ROX, and L leads to G are significantly higher in the running dog. Exercise increased the metabolic clearance rate of lactate threefold. At rest ROX and L leads to G represented about 50% and 18-19% of RdL, respectively. The corresponding values in the running dogs were 55% and 25%, respectively. At rest about 9% of the hepatic glucose output arose from lactate while during exercise this varied from 7 to 26% depending on RdL. It is concluded that a) the working muscle produces and utilizes lactate at the same time, and b) "in vivo" the major factor which controls both ROX and gluconeogenesis is the substrate supply.

Animals↗
PubMed1975

Interrelationship of FFA and glycerol turnovers in resting and exercising dogs.

Dogs with indwelling arterial and venous catheters ran on a treadmill on a 10% or on a 15% slope at 100 m/min. Glycerol turnover ([2-3H]-glycerol) and FFA turnover ([1-14C]palmitate) were measured simultaneously. Both turnovers were greatly increased by exercise. Similar increases were produced in resting dogs by norepinephrine infusions (0.5 mug/kg-min). At rest, as well as during exercise, there was a straight-line correlation between the ratio of disappearance of each substrate and their respective plasma concentrations. Over a wide range there was a straight-line correlation between the rate of production of FFA (RaFFA) and that of glycerol (RaGLY) at rest as well as during exercise. At any given RaFFA, RaGLY was higher in the running than in the resting dog. At rest the ratio of RaFFA/RaGLY was found to give the theoretical value of 3.0 only when RaFFA was 10-15 mumol/kg-min, below this the ratio was lower and above this it was higher. During exercise the ratio was lower than at rest and at heavier load lower than at lighter work. The results suggest that in vivo a combination of partial and complete lipolysis as well as reesterification occurs. The glucose equivalent of the glycerol turnover (if 100% converted) represents (under the given experimental conditions) 14-18% of the hepatic glucose output on the 15% slope and 20-25% of it on the 10% slope.

Adipose Tissue↗
PubMed1975

Effect of lactate on FFA and glycerol turnover in resting and exercising dogs.

The rates of appearance of FFA (RaFFA) and that of glycerol (RaGLY) were measured simultaneously with [1-14 C]palmitate and [2-3H]-glycerol, in dogs with indwelling arterial and venous catheters. Lipolysis was stimulated by exercise (treadmill run on 10% slope) or by the infusion of norepinephrine (0.5 mug/kg-min). Na-L(+)-lactate (L), Na-pyruvate (Py), or Na-nicotinate (N) were infused. All three components decreased RaFFA. RaGLY was increased by L, unaltered by Py, and decreased by N. There was an inverse correlation (P less than 0.001) between the logarithms of RaFFA and plasma lactate. A linear correlation was obtained between RaGLY and plasma lactate when this latter was increased by the infusion of L. It is suggested that a) lactate in physiological concentrations inhibits the release of FFA stimulated by exercise and b) the increase of the NADH/NAD ratio leads to the formation of alpha-glycerophosphate which in turn yields glycerol. Therefore changes in plasma glycerol do not reflect lipolysis when blood lactate increases. c) The effect of lactate on RaFFA can be explained by an enhanced reesterification, although a direct inhibition on lipase could not be excluded.

Animals↗
PubMed1975

Glucose turnover in the exercising dog with chemically induced diabetes and the effect of methylprednisolone.

Dogs with indwelling polyethylene arterial and venous catheters ran on a treadmill (slope 15 per cent, speed 100 m./min.). Diabetes was produced by alloxan or by a combination of alloxan and streptozotocin. Glucose turnover was measured according to the primed constant-rate infusion technics with 2-3H-glucose as tracer. In resting diabetic dogs plasma glucose varied between 200 and 650 mg./100 ml. There was a direct linear correlation between the hepatic glucose output (Ra) and the plasma glucose level. Exercise increased both Ra and the clearance rate (CR) of glucose; however, Ra could not match the rate of disappearance (=renal loss plus glucose uptake of the muscle), causing the plasma glucose to decline more rapidly than in the running control dogs. Two to three days' treatment with methylprednisolone (MP, 3-3.2 mg./kg./day) caused a higher resting glucose level and a higher Ra. Exercise greatly increased the plasma glucose concentration, partly because MP enhanced the hepatic response but mainly because it essentially prevented the rise of CR. It is concluded that (a) in chemically induced diabetes, the variable glucose level is the result of a variable rate of hepatic glucose output; (b) the increase of Ra by MP treatment does not increase the plasma glucose in the normal dog but significantly aggravates the alloxan diabetes, (c) diabetes reduces the effect of exercise on the glucose uptake of the muscle, and this effect is potentiated by the inhibitory action of the glucocorticoid. This latter becomes unmasked only when the insulin secretion is impaired.

Animals↗