Changes in glycogen metabolism after an intravenous injection of angiotensin II were investigated in the left and right ventricles of the rat heart, as a function of location within the ventricular ...wall. Hearts were cut into 100-microns thin section, all of which were analysed for glycogen content, glucose incorporation into glycogen and 2-deoxyglucose uptake and phosphorylation after the intravenous injection of 14C-labelled sugar. In control hearts, glycogen levels were uniform across the wall in both ventricles, while the rate of sugar uptake and phosphorylation, and that of glucose incorporation into glycogen, were significantly higher in the subendocardial myocardium of the left ventricular wall. After angiotensin II administration, heart glycogen levels decreased slightly in the left, but not in the right ventricle, while 2-deoxyglucose uptake and phosphorylation, and glucose incorporation into glycogen, increased 2,5- and 5-fold, respectively. With regard to the distribution across the wall of the left ventricle after angiotensin administration, glycogen levels and glucose incorporation into glycogen were uniformly distributed, whereas sugar phosphorylation was still higher in the subendocardium.
The age-related changes in the activities of five glucose-metabolizing enzymes (hexokinase, HK; glucose-6-phosphate dehydrogenase, G6P-DH; aldolase, ALD; phosphofructokinase, PFK; and lactate ...dehydrogenase, LDH) were investigated in the walls of left and right ventricles of rats of various age-groups (1-24 months). Age-related changes were found in the activities of all of the enzymes in both ventricles during growth (with significant decreases between 2 and 6 months of age) and in the levels of PFK and LDH in the left ventricle during ageing (with a significant increase between 12 and 24 months of age). The distribution of the enzyme activities across the wall of both ventricles was quite uniform in young, adult and mature rats (the distribution of G6P-DH activity in the left ventricle wall at 2 months of age was the only notable exception) but became non-uniform in the old rats with regard to G6P-DH, PFK, LDH and probably HK in the left ventricle and G6P-DH and HK in the right ventricle. These data support the hypothesis that alterations connected with ageing do not lead to a generalized decline of cardiac metabolic capacity, and that they are also the result of specific adaptive modifications, perhaps related to alteration in the distribution of the work load and/or of nutrition across the ventricular wall.
Male Sprague-Dawley rats were treated with triiodothyronine (100 micrograms/100 g/day) for 2, 4, 7, 14 and 21 days and the biochemical and ultrastructural changes of the brown adipose tissue were ...investigated. Results showed that the tissue weight, DNA and phospholipid content increased very early (by day 2 or 4) and that triglycerides increased later. These hormonal effects are not inhibited by the beta 1-antagonist propranolol. From the morphological point of view, triiodothyronine administration induced the early proliferation and maturation of adipocyte precursors (interstitial cells and preadipocytes). It is concluded that triiodothyronine administration causes a very early hyperplasia in the brown adipose tissue similar to that observed during exposure to cold by mechanisms that may not be secondary to the involvement of norepinephrine.
The concentrations of the adenosine-generating enzyme 5'-nucleotidase (5'-N) and of the adenosine-degrading enzyme adenosine deaminase (ADA) in the rat left ventricle change as a function of the age ...of the animal. The enzyme distribution across the left ventricle wall is non-uniform in adult or old rats (in the case of 5'-N) or in all age-groups (in the case of ADA). In the oldest rats, 5'-N activity exhibited a significant increase in the mid-myocardium and in the inner myocardial layers as compared with the young adult controls.
The effects of low doses of vanadyl sulfate (0.2 mg/ml in the drinking water) on the age-related impairment of glucose homeostasis in Sprague-Dawley rats were investigated. VOSO(4) administration was ...initiated in 5-month-old animals and lasted 3 months. Thus, in 8-month-old rats, we investigated glucose metabolism in vivo and insulin secretory function in vitro. Results showed that VOSO(4) allowed the disposal of an oral glucose load at lower insulin levels than in age-matched controls. No significant changes were found in muscle glucose transporter (GLUT-4) levels or in glycogen content upon VOSO(4) treatment. Islets isolated from VOSO(4)-treated rats released less insulin than control islets, but showed a better preserved sensitivity to secretagogues, in terms of incremental release over basal release, secretory efficiency, and maintenance of the priming effect of glucose. In conclusion, chronic low-dose VOSO(4) treatment facilitates insulin action by a mechanism independent of muscle GLUT-4 levels and helps preserve the appropriate sensitivity of beta cells to stimuli, thereby preventing age-dependent functional alterations.
Changes in glycogen metabolism were explored in fast and slow muscles taken from rats fed with a diet containing 1% beta-guanidine propionate (GPA), a synthetic analog that inhibits the entry of ...creatine into muscle cells competitively and causes phosphorylcreatine depletion. Feeding with the GPA-containing diet increased glycogen levels in the two types of muscles to a different extent and with different temporal patterns; it did not change significantly the rate of glycogen turnover both at rest and during exercise; it did not affect the net degradation of glycogen during exercise. Diet could affect the activity of several enzymes of sugar metabolism. These latter changes too were different in fast-twitch and in slow-twitch muscles.
The effects of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on the proliferation, protein kinase C activity (PKC), and c-fos gene expression were examined in cultures of young and ...senescent (90-95% lifespan completed) WI-38 human diploid fibroblasts. We observed that, following stimulation with medium containing 10% fetal bovine serum (FBS), the translocation of PKC from the cytosol to the particulate compartment was less efficient in senescent WI-38 cells than in young cells. However, when PMA was added to the medium, the intracellular distribution of PKC activity in old cells became nearly identical to that observed in young cells. The inducibility of c-fos mRNA by serum addition, which is a protein kinase C-dependent event, was significantly amplified in the presence of PMA. Moreover, the duration of peak c-fos expression, after stimulation by FBS and PMA, increased in senescent cells as compared to young cells. Our results reveal that the normal signal transduction pathway is altered in senescent, slowly proliferating human fibroblasts and that it can be partially restored in the presence of the tumor promoter PMA.
The changes of glycogen metabolism with the location of tissue within the ventricle wall have been explored in the rat myocardium. The hearts were cut in 100 microns thick serial sections and all ...sections were analyzed for their content in glycogen, glucose-6-phosphate, UDPG and glycogen enzymes and for glucose incorporation into glycogen and for the 2-deoxyglucose uptake after the intravenous injection of the 14C-labelled sugars. The rate of glycogen turnover was significantly higher in the subendocardial myocardium (P less than 0.01) and the levels of glucose-6-phosphate and the total (i.e. a + b) activity of glycogen phosphorylase were significantly higher in the subepicardial tissue (P less than 0.01 in both instances). No significant transmural gradient of UDPG was found and transmural changes of total (i.e. I + D) synthase activity were barely significant. These changes in glycogen metabolism may be related to regional differences in the cardiac work load and to a differentiation of the subendocardial and subepicardial heart fibers.
A dramatic increase in the plasma glucagon/insulin ratio can be induced by treating fasted rats with antilipolytic drugs (e.g., with 3,5-dimethylpyrazole, 12 mg/kg body wt). These hormone changes are ...the physiologically appropriate response to a rapid decrease in free fatty acids and glucose plasma levels. Under this experimental condition, many vacuolated lysosomes can be observed at the electron microscopic level as early as 30 min and autophagic vacuoles are detectable in the liver cells 1 hr after the administration of the drug. By 1 hr and 45 min, vacuoles often contain recognizable peroxisomes. At the biochemical level, liver proteolysis in vitro is increased significantly. Very interestingly, changes in peroxisomal (but not mitochondrial or reticulum or cytosolic) enzyme activities are detected that are preventable by the administration of glutamine (i.e., of an inhibitor of proteolysis in vivo) but not by an isocaloric amount of glycine or alanine. It is concluded that the administration of antilipolytic agents to fasted animals may provide a convenient (i.e., an inexpensive, highly reproducible and timable) physiologic model to study hormone-induced autophagy in liver cells.
