scholarly journals Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats

1971 ◽  
Vol 124 (3) ◽  
pp. 475-490 ◽  
Author(s):  
L. H. Opie ◽  
K. R. L. Mansford ◽  
P Owen

1. In the isolated perfused rat heart, the contractile activity and the oxygen uptake were varied by altering the aortic perfusion pressure, or by the atrial perfusion technique (‘working heart’). 2. The maximum increase in the contractile activity brought about an eightfold increase in the oxygen uptake. The rate of glycolytic flux rose, while tissue contents of hexose monophosphates, citrate, ATP and creatine phosphate decreased, and contents of ADP and AMP rose. 3. The changes in tissue contents of adenine nucleotides during increased heart work were time-dependent. The ATP content fell temporarily (30s and 2min) after the start of left-atrial perfusion; at 5 and 10min values were normal; and at 30 and 60min values were decreased. ADP and AMP values were increased in the first 15min, but were at control values 30 or 60min after the onset of increased heart work. 4. During increased heart work changes in the tissue contents of adenine nucleotide and of citrate appeared to play a role in altered regulation of glycolysis at the level of phosphofructokinase activity. 5. In recirculation experiments increased heart work for 30min was associated with increased entry of [14C]glucose (11.1mm) and glycogen into glycolysis and a comparable increase in formation of products of glycolysis (lactate, pyruvate and 14CO2). There was no major accumulation of intermediates. Glycogen was not a major fuel for respiration. 6. Increased glycolytic flux in Langendorff perfused and working hearts was obtained by the addition of insulin to the perfusion medium. The concomitant increases in the tissue values of hexose phosphates and of citrate contrasted with the decreased values of hexose monophosphates and of citrate during increased glycolytic flux obtained by increased heart work. 7. Decreased glycolytic flux in Langendorff perfused hearts was obtained by using acute alloxan-diabetic and chronic streptozotocin-diabetic rats; in the latter condition there were decreased tissue contents of hexose phosphates and of citrate. There were similar findings when working hearts from streptozotocin-diabetic rats with insulin added to the medium were compared with normal hearts. 8. The effects of insulin addition or of the chronic diabetic state could be explained in terms of an action of insulin on glucose transport. Increased heart work also acted at this site, but in addition there was evidence for altered regulation of glycolysis mediated by changes in tissue contents of adenine nucleotides or of citrate.

2002 ◽  
Vol 282 (1) ◽  
pp. E74-E79 ◽  
Author(s):  
Gregory J. Crowther ◽  
William F. Kemper ◽  
Michael F. Carey ◽  
Kevin E. Conley

Glycolytic flux in muscle declines rapidly after exercise stops, indicating that muscle activation is a key controller of glycolysis. The mechanism underlying this control could be 1) a Ca2+-mediated modulation of glycogenolysis, which supplies substrate (hexose phosphates, HP) to the glycolytic pathway, or 2) a direct effect on glycolytic enzymes. To distinguish between these possibilities, HP levels were raised by voluntary 1-Hz exercise, and glycolytic flux was measured after the exercise ceased. Glycolytic H+ and ATP production were quantified from changes in muscle pH, phosphocreatine concentration, and Pi concentration as measured by 31P magnetic resonance spectroscopy. Substrate (HP) and metabolite (Pi, ADP, and AMP) levels remained high when exercise stopped because of the occlusion of blood flow with a pressure cuff. Glycolytic flux declined to basal levels within ∼20 s of the end of exercise despite elevated levels of HP and metabolites. Therefore, this flux does not subside because of insufficient HP substrate; rather, glycolysis is controlled independently of glycogenolytic HP production. We conclude that the inactivation of glycolysis after exercise reflects the cessation of contractile activity and is mediated within the glycolytic pathway rather than via the control of glycogen breakdown.


1982 ◽  
Vol 60 (7) ◽  
pp. 960-967 ◽  
Author(s):  
X. Pascaud ◽  
J. P. Ferre ◽  
M. Genton ◽  
A. Roger ◽  
M. Ruckebusch ◽  
...  

Myoelectrical and mechanical activities were chronically recorded by use of nichrome electrodes and miniaturized strain-gage transducers sutured on the serosa of the antrum, the duodenum, and the jejunum, in a first experiment (n = 6 rats) the early (0–6 h) and late (> 4 days) effects of streptozotocin (65 mg/kg i.v.) was recorded. In addition, the effect of insulin (1–5 IU/kg) and glucagon (6–200 μg/kg) administered intravenously were studied separately each in groups of seven normal and streptozotocin-induced diabetic-fed and fasted rats. The results indicated that within the 30 min following streptozotocin administration there was a significant stimulation of the duodenal and jejunal motility lasting 46 ± 8 min. When diabetes was established as shown by the basal blood glucose level obtained in those rats (2.30 ± 0.84 g/L), a progressive decrease of the frequency of the migrating myoelectric complex was observed along with a disorganization of the regular spiking activity phases without disturbing the basal electrical rhythm. Comparing with the basal level, a significant increase in the gastrointestinal motility indexes (MI) appeared both in fasted (p < 0.01) and fed (p < 0.05) normal animals, 13.1 ± 1.6 min after an i.v. injection of 1 IU/kg insulin. Motor effects of glucagon were related to the dose. When used at 25 μg/kg a disorganization of the spiking activity was observed with a stimulation of the contractile activity in the jejunum. At higher dosages, i.e., 100 μg/kg, it induced an immediate and significant decrease of motility at any level tested and lasting up to 20 ± 7 min. The motility responses to both hormones were lower in diabetic than in normal rats.


1986 ◽  
Vol 64 (2) ◽  
pp. 485-489 ◽  
Author(s):  
A. Lazou ◽  
I. Beis

In the isolated, perfused Rana ridibunda heart, the concentrations of the metabolites were measured as a function of time, under increased heart work. The changes in tissue contents of adenine nucleotides were time dependent. ADP, AMP, and inorganic phosphate levels increased simultaneously, while ATP and creatine phosphate levels decreased. The tissue contents of hexose monophosphates and citrate decreased and contents of fructose bisphosphate, lactate, and pyruvate rose. A comparison of mass action ratios with apparent equilibrium constants for the glycolytic reactions indicated that phosphoglucose isomerase, aldolase, triosephosphate isomerase, and lactate dehydrogenase reactions are close to equilibrium, while phosphofructokinase is displaced from equilibrium. During increased heart work, changes in the tissue contents of adenine nucleotides and citrate appeared to play a role in the regulation of glycolysis at the level of phosphofructokinase activity. From the results, it appears that in amphibian heart, glycolysis seems to be similar to that of mammalian heart as far as control is concerned, in spite of its structural and functional differences.


1991 ◽  
Vol 266 (14) ◽  
pp. 8671-8674
Author(s):  
E. Unger ◽  
I. Pettersson ◽  
U.J. Eriksson ◽  
U. Lindahl ◽  
L. Kjellén

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