Effects of ventricular pressure development and palmitate on glucose transport

1. Concentrations of citrate, hexose phosphates and glycogen were measured in skeletal muscle and heart under conditions in which plasma non-esterified fatty acids and ketone bodies were physiologically increased. The aim was to determine under what conditions the glucose-fatty acid cycle might be operative in skeletal muscle in vivo. 2. In keeping with the findings of others, starvation increased the concentrations of glycogen, citrate and the fructose 6-phosphate/fructose 1,6-bisphosphate ratio in heart, indicating that the cycle was operative. In contrast, it decreased glycogen and had no effect on the concentration of citrate or the fructose 6-phosphate/fructose 1,6-bisphosphate ratio in the soleus, a slow-twitch red muscle in which the glucose-fatty acid cycle has been demonstrated in vitro. 3. In fed rats, exercise of moderate intensity caused glycogen depletion in the soleus and red portion of gastrocnemius muscle, but not in heart. In starved rats the same exercise had no effect on the already diminished glycogen contents in skeletal muscle, but it decreased cardiac glycogen by 2530% . 4. After exercise, citrate and the fructose 6-phosphate/fructose 1,6-bisphosphate ratio were increased in the soleus of the starved rat. Significant changes were not observed in fed rats. 5. The data suggest that in the resting state the glucose-fatty acid cycle operates in the heart, but not in the soleus muscle, of a starved rat. In contrast, the metabolite profile in the soleus was consistent with activation of the glucose-fatty acid cycle in the starved rat during the recovery period after exercise. Whether the cycle operates during exercise itself is unclear.

supporting

confidence: 89%

Effects of starvation and exercise on concentrations of citrate, hexose phosphates and glycogen in skeletal muscle and heart. Evidence for selective operation of the glucose-fatty acid cycle

Zorzano¹,

Balon²,

Brady³

et al. 1985

“…Importantly, it was found that glucose transport is depressed not only by fatty acids and ketone bodies, as described in studies on heart [1,15] and skeletal muscle [16], but also, and to a larger extent, by other substrates and metabolites such as pyruvate, lactate and propionate. Moreover, the present work demonstrates for the first time that there is a tight coupling between intermediary metabolism and the glucose transport system in these cells.…”

Section: Discussionmentioning

confidence: 59%

“…Conversely, substrates (such as lactate, pyruvate, acetate and propionate) induce an elevation in α-oxoglutarate and a fall in aspartate in heart [32][33][34]40,45]. Moreover, increased cardiac work, which is known to stimulate glucose transport [15], was reported to markedly increase the aspartate level [45]. In view of all these observations, further investigations should be focused on a potential role of products of transamination reactions as effectors of the glucose transport system.…”

Section: Coupling Of Intermediary Metabolism and Glucose Transportmentioning

confidence: 99%

See 1 more Smart Citation

Glucose transport and glucose transporter GLUT4 are regulated by product(s) of intermediary metabolism in cardiomyocytes

Fischer

Böttcher

Eblenkamp

et al. 1997

Alternative substrates of energy metabolism are thought to contribute to the impairment of heart and muscle glucose utilization in insulin-resistant states. We have investigated the acute effects of substrates in isolated rat cardiomyocytes. Exposure to lactate, pyruvate, propionate, acetate, palmitate, β-hydroxybutyrate or α-oxoglutarate led to the depression of glucose transport by up to 50 %, with lactate, pyruvate and propionate being the most potent agents. The percentage inhibition was greater in cardiomyocytes in which glucose transport was stimulated with the α-adrenergic agonist phenylephrine or with a submaximal insulin concentration than in basal or fully insulin-stimulated cells. Cardiomyocytes from fasted or diabetic rats displayed a similar sensitivity to substrates as did cells from control animals. On the other hand, the amination product of pyruvate (alanine), as well as valine and the aminotransferase inhibitors cycloserine and amino-oxyacetate, stimulated glucose transport about 2-fold. In addition, the effect of pyruvate was counteracted by cycloserine. Since reversible transamination reactions are known to affect the pool size of the citrate cycle, the influence of substrates, amino acids and aminotransferase

“…Further, although the stimulation of glucose uptake by insulin is decreased in both tissues by diabetes, free fatty acids and ketone bodies cause a similar inhibition only in heart. Finally, the stimulatory effect of exercise on the uptake of glucose is not diminished by fatty acids or ketone bodies in the hindquarter, whereas the fatty acids markedly decrease the increase in-cardiac glucose utilization caused by an increment in intraventricular pressure (Neely et al, 1969).…”

Section: Vol 158mentioning

confidence: 85%

Glucose metabolism in perfused skeletal muscle. Effects of starvation, diabetes, fatty acids, acetoacetate, insulin and exercise on glucose uptake and disposition

Berger¹,

Hagg²,

Goodman³

et al. 1976

182

1. The regulation of glucose uptake and disposition in skeletal muscle was studied in the isolated perfused rat hindquarter. 2. Insulin and exercise, induced by sciatic-nerve stimulation, enhanced glucose uptake about tenfold in fed and starved rats, but were without effect in rats with diabetic ketoacidosis. 3. At rest, the oxidation of lactate (0.44,umol/ mi per 30g ofmuscle in fed-rats) was decreased by 75% in both starved and diabetic rats, whereas the release of alanine and lactate (0.41 and 1.35,umol/min per 30g respectively in the fed state) was increased. Glycolysis, defined as the sum of lactate+alanine release and lactate oxidation, was not decreased in either starvation or diabetes. 4. In all groups, exercise tripled 02 consumption (from -8 to -25umol/min per 30g of muscle) and increased the release and oxidation of lactate five-to ten-fold. The differences in lactate release between fed, starved and diabetic rats observed at rest were no longer apparent however, lactate oxidation was still several times greater in the fed group. 5. Perfusion of the hindquarter ofa fed rat with palmitate, octanoate or acetoacetate did not alter glucose uptake or lactate release in either resting or exercising muscle; however, lactate oxidation was significantly inhibited by acetoacetate, which also increased the intracellular concentration of acetyl-CoA. 6. The data suggest that neither glycolysis nor the capacity for glucose transport are inhibited in the perfused hindquarter during starvation or perfusion with fatty acids or ketone bodies. On the other hand, lactate oxidat-ion is inhibited, suggesting diminished activity ofpyruvate dehydrogenase. 7. Differences in the regulation of glucose metabolism in heart and skeletal muscle and the role of the glucose/fatty acid cycle in each tissue are discussed.The present paper deals with the alterations in muscle-glucose metabolism that occur in starvation and diabetes and therole offreefatty acids and ketone bodies in causing these changes. Much of our present knowledge of this subject has been derived from experiments carried out in the perfused rat heart. Using this preparation, Randle et al. (1966) observed an inhibition of the tiptake, phosphorylation and oxidation of glucose and a -block in glycolysis at the level-of phosphofructokitase both in starvation and diabetes. In iddition, they obsrved a similar pattern in hearts perfused with fatty acids and ketone bodies, whichiled themto stggest that the increased utilization of these substrates in starved and diabetic rats might explain the impaired -glucose metabolism in these states. Comparable findings have been observed in diaphragm by some laboratories but not others (see Ruderman et al., 1969).