Enhancement in the activities of mouse epidermal glucose-6-phosphate dehydrogenase, hexokinase, phosphofructokinase, and pyruvate kinase by 12-O-tetradecanoyl-phorbol-13-acetate

The active ingredient in the tumor-promoting croton oil, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), was shown to increase the activity of mouse skin epidermal glucose-6-phosphate dehydrogenase (+84%), hexokinase (+100%), phosphofructokinase (+158%), and pyruvate kinase (+101%). This increase in activity of these key enzymes of glucose metabolism occurred 2-8 h after TPA application and was due to a net increase in the enzyme content. This increase in the activity of the glycolytic enzymes, as well as the reported TPA-induced increase in the synthesis of RNA and DNA and cell proliferation, suggest that activation of the glycolytic pathway may be involved in the carcinogenic effects of tumor promoters.     

Age-related changes in rat adipose tissue in response to fasting: protein, lactate and pyruvate levels

1. The evolution with age of the metabolic response of adipose tissue to fasting has been investigated in two groups of rats, at different ages, fed and fasted. 2. The protein tissue content increases in response to fasting in young rats but not in adult-old ones. This indicates a lower lipomobilizing response to starvation with increasing age. 3. In contrast to young rats, the adult rat lactate is not increased by fasting while pyruvate is increased. 4. As a result of lactate and pyruvate variations, NAD/NADH is also changed: after fasting it decreases in young rats, while it increases in older rats. 5. Absolute NAD level is decreased by fasting both in young and older rats. 6. These data provide experimental support for the decreased sensitivity of fat pads from older animals to stimuli affecting lipolysis.     

Stimulation of pyruvate dehydrogenase activity by insulin-dextran complex in mouse adipose tissue.

Soluble and stable insulin-dextran complex was prepared. Pyruvate dehydrogenase activity, as assayed by ¹⁴CO₂ formation from [1-¹⁴C]-pyruvate in crude mitochondria of mouse adipose tissue, was increased after incubation of fat pads with native insulin or insulin-dextran. The direct addition of insulin or insulin-dextran to mitochondria was without effect. At submaximal stimulation, insulin-dextran was 10 times less effective than native insulin but the degree of maximal stimulation and the time course of activation by insulin and insulin-dextran were similar. The results favor the concept that the activation of pyruvate dehydrogenase in fat cells does not need the entry of insulin into cells.     

Effect of mandur bhasma on lipolytic activities of liver,kidney and adipose tissue of albino rat during CCl4 induced hepatic injury

‘Mandur bhasma’, an ayurvedic preparation of iron is used in traditional medicine against hepatitis. In the present study the hepatoprotective property of this drug was tested in albino rats during CC1₄ induced hepatic injury. The effect of mandur bhasma on the activities of the lipolytic enzymes of rat liver, kidney and adipose tissue were studied during hepatitis induced by CCl₄. The activities of acid lipase, alkaline lipase, lipoprotein lipase and hormone sensitive lipase exhibited significant alterations during CCl₄ induced hepatic injury, indicating a role for these enzymes in the mobilization of fat from adipose tissue and accumulation of fat in liver and kidney. Simultaneous treatment with mandur bhasma prevented the paraffin mediated and CC1₄ mediated changes in the enzyme activities. These results suggest the hepatoprotective role of mandur bhasma during CCl₄ induced hepatic injury.     

Hepatic pyruvate dehydrogenase kinase activities during the starved-to-fed transition.

Starvation for 48 h elicited a 74% increase in hepatic pyruvate dehydrogenase (PDH) kinase activity, measured directly by 32Pi-incorporation from [gamma-32P]ATP into a synthetic peptide corresponding to the major phosphorylation site on E1. The administration of chow ad libitum to previously-starved rats suppressed hepatic PDH kinase activity by only approx. 20% within 2 h of re-feeding, and the relatively high activity of PDH kinase was associated with continued suppression of PDC complex re-activation. Whereas there was no further decline in PDH kinase activity over the next 2 h, PDC re-activation to the fed value was observed during this time interval. PDH kinase activity decreased to fed values only after 8 h.     

The regulation of adipose tissue pyruvate dehydrogenase activity of dietary fiber

In vitro studies have established that insulin enhances the oxidation of pyruvate to acetyl CoA by the stimulation of mitochondrial pyruvate dehydrogenase (PDH) activity through plasma membrane binding response (Jarett and Seals 1979; Kiechle, Jarett, Dennis and Kotagal 1980). In the present study adipose tissue PDH activity was utilized as a marker for insulin responsiveness. The metabolic response of this enzyme to exogenous insulin was employed to test the hypothesis that dietary fiber enhances tissue responsiveness to insulin using adipose tissue from male weanling Sprague Dawley rats. Eight groups of rats (n = 5 per group) were fed ad libitum various diets containing different levels of cellulose and protein as already reported elsewhere (Ogunwole, Knight, Adkins, Thomaskutty and Pointer 1985). Percent insulin stimulation of PDH from basal activity (PDS) was utilized as an index of insulin responsiveness. Compared to all fiber treated groups, both basal (PDB) and insulin stimulated (PDI) activities were significantly lower (P less than 0.05) in the fiber free groups at both low (10%) and high (20%) protein levels. At all fiber levels tested (0, 5, 15 and 30%) protein intake resulted in a significant increase in both PDB and PDI. Gradual increase in cellulose intake resulted in a biphasic increase in PDS in both protein groups at the 5% and 30% fiber levels. PDS was higher (P less than 0.05) in the 10% protein groups than the 20% protein group at all fiber levels tested. A significant interaction effect of protein and fiber was observed on PDB (P less than 0.001) and PDI (P less than 0.04) when caloric intake was held constant as a covariate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Catecholamine activation of pyruvate dehydrogenase in white adipose tissue of the rat in vivo.

Intraperitoneal injections of noradrenaline or adrenaline into rats increased the proportion of pyruvate dehydrogenase in the active state in white adipose tissue; this effect of catecholamines was also apparent in streptozotocin-diabetic rats, showing that it was not due to an increase in serum insulin concentration. The catecholamine-induced increase in pyruvate dehydrogenase of white adipose tissue in vivo was completely blocked by prior injection of either the beta-antagonist propranolol or the alpha 1-antagonist prazosin. Cervical dislocation of conscious rats increased pyruvate dehydrogenase activity of white adipose tissue, which was prevented by prior injection of propranolol. Adrenaline (30 nM) activated pyruvate dehydrogenase in white adipocytes in vitro; the maximum effect of adrenaline required activation of both alpha 1- and beta-receptors. The results show that catecholamines activate pyruvate dehydrogenase of white adipose tissue both in vivo and in vitro and that this effect is mediated by a combination of alpha 1- and beta-adrenergic receptors.     

Age-related characteristics of the effect of periodic low-calorie nutrition on lipid composition of the liver cells, small intestine, adipose tissue and blood serum in albino rats

It is studied how long-term periodical calorie-insufficient and growth-restraining nutrition promoting appreciable life prolongation in the Wistar-line albino rats influences the lipid metabolism. It is shown that diet has an essential influence on the levels of phospholipids, cholesterol, neutral lipids, fatty acids in different tissue cells. The age specificity is observed in all the studied tissue cells. The lipid composition of cells in aged rats with prolonged life is similar to that of young animals of control group.