Metabolic interactions of glucose, acetoacetate and adrenaline in rat submaxillary gland in vitro

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.

mentioning

confidence: 58%

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

“…It has been proposed by Hawkins & Williamson (1972) that the decreased glucose uptake and increased lactate output in vivo could result from 1977 increased metabolism of ketone bodies, as has been found for other rat tissues (Williamson & Krebs, 1961;Randle et al, 1964;Thompson & Williamson, 1975). A decreased insulin concentration has also been suggested as a possible cause for the decreased glucose uptake in starvation (Williamson etal., 1975), but as yet the concentrations of insulin and prolactin have not been measured in starved lactating rats.…”

Section: Starvation and The Mammary Glandmentioning

confidence: 93%

Comparison of glucose metabolism in the lactating mammary gland of the rat in vivo and in vitro. Effects of starvation, prolactin or insulin deficiency

Robinson

Williamson

1977

1. Measurements of arteriovenous differences across mammary glands of normal and starved lactating rats, and lactating rats made short-term insulin-deficient with streptozotocin or prolactin-deficient with bromocryptine, showed that only in the starved animals was there a significant decrease in glucose uptake. This decrease was accompanied by release of lactate and pyruvate from the gland, in contrast with the uptake of these metabolites by glands of normal lactating rats. 2. There were no marked differences in metabolite concentrations in freeze-clamped glands in the four conditions studied, apart from a decrease in [lactate] and [pyruvate] and an increase in [glucose] in the glands of the streptozotocin-treated group. 3. Acini isolated from the glands of starved, insulin or prolactin-deficient rats had a higher production of lactate and pyruvate from glucose than did glands from normal rats; this is in agreement with the reported decrease in the proportion of active pyruvate dehydrogenase in these situations [Field & Coore (1976) Biochem. J.156, 333-337; Kankel & Reinauer (1976) Diabetologia12, 149-154]. 4. Addition of insulin did not increase the uptake of glucose by acini from normal glands, but it caused a significant increase in the utilization of glucose by acini from glands of starved rats. Insulin did not decrease the accumulation of lactate and pyruvate in any of the experiments. 5. It is concluded that isolated acini represent a suitable model for the study of mammary-gland carbohydrate metabolism in that they reflect metabolism of the gland in vivo.

“…Inhibition of glucose uptake by free fatty acids and/or ketone bodies has been noted in diaphragm (Randle et al, 1966) and in mammary (Williamson, 1973) and submaxillary (Thompson & Williamson, 1975) glands as well as in heart. In addition, indirect evidence suggests that ketone bodies may inhibit the utilization ofglucose by brain .…”

Section: Vol 158mentioning

confidence: 99%

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).