Effects of glucocorticoids on adenyl cyclase and phosphodiesterase activity in fat cell homogenates and the accumulation of cyclic AMP in intact fat cells

1972 ◽  
Vol 273 (3) ◽  
pp. 267-282 ◽  
Author(s):  
P. S. Sch�nh�fer ◽  
I. F. Skidmore ◽  
M. I. Paul ◽  
B. R. Ditzion ◽  
G. L. Pauk ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Adenyl Cyclase ◽  
Fat Cells ◽  
Phosphodiesterase Activity ◽  
Fat Cell

scholarly journals Short-term hyperthyroidism modulates adenosine receptors and catalytic activity of adenylate cyclase in adipocytes

1987 ◽  
Vol 241 (3) ◽  
pp. 765-771 ◽  
Author(s):  
P J Rapiejko ◽  
C C Malbon
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Adenosine Deaminase ◽  
Catalytic Subunit ◽  
Inhibitory Influence ◽  
Fat Cells ◽  
Adenylate Cyclase System ◽  
Fat Cell ◽  
Short Term ◽  
Receptor Number

The effects of short-term hyperthyroidism in vivo on the status of the components of the fat-cell hormone-sensitive adenylate cyclase were investigated. The number of beta-adrenergic receptors was elevated by about 25% in membranes of fat-cells isolated from hyperthyroid rats as compared with euthyroid rats, but their affinity for radioligand was unchanged. Membranes of hyperthyroid-rat fat-cells displayed less than 65% of the normal complement of receptors for [3H]cyclohexyladenosine. The affinity of the receptors for this ligand was normal. In contrast with the marked increase in the amounts of the alpha-subunits of the guanine nucleotide-binding proteins Gi (Mr 41,000) and Go (Mr 39,000) observed in the hypothyroid state [Malbon, Rapiejko & Mangano (1985) J. Biol. Chem. 260, 2558-2564], the amounts of alpha-Gi, alpha-Go as well as alpha-Gs subunits [Mr 42,000 (major) and 46,000/48,000 (minor)] were not changed by hyperthyroidism. Adenylate cyclase activity in response to forskolin, guanosine 5′-[gamma-thio]triphosphate or isoprenaline, in contrast, was decreased by 30-50% in fat-cell membranes from hyperthyroid rats. Fat-cells isolated from hyperthyroid rats accumulated cyclic AMP to less than 50% of the extent in their euthyroid counterparts in the presence of adenosine deaminase and either adrenaline or forskolin, suggesting a decrease in the amount or activity of the catalytic subunit of adenylate cyclase. In the absence of exogenous adenosine deaminase, cyclic AMP accumulation in response to adrenaline was elevated rather than decreased in fat-cells from hyperthyroid rats. The inhibitory influence of adenosine is apparently limited in the hyperthyroid state by the decreased complement of inhibitory R-site purinergic receptors in these fat-cells. Short-term hyperthyroidism modulates the fat-cell adenylate cyclase system at the receptor level (beta-receptor number increased, R-site purinergic-receptor number decreased) and the catalytic subunit of adenylate cyclase.

STUDIES ON THE MECHANISMS OF SOMATOSTATIN ACTION ON INSULIN RELEASE

1977 ◽  
Vol 85 (2) ◽  
pp. 379-388 ◽  
Author(s):  
A Claro ◽  
V. Grill ◽  
S. Efendić ◽  
R. Luft
Keyword(s):  
Cyclic Amp ◽  
Insulin Release ◽  
Competitive Inhibition ◽  
Phosphodiesterase Inhibitor ◽  
Adenyl Cyclase ◽  
Phosphodiesterase Activity ◽  
High Concentration ◽  
Isolated Islets Of Langerhans ◽  
Cyclic Amp Accumulation ◽  
Effect Of Glucose

ABSTRACT The effects of somatostatin on insulin release and cyclic AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Concentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cyclic AMP accumulation induced by 16.7 mm glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H] cyclic AMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H] cyclic AMP accumulation induced by the phosphodiesterase inhibitor, IBMX, while no inhibition was seen, again in the absence of hexose, when the [3H] cyclic AMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30 %. It is suggested that somatostatin-induced inhibition of insulin release is, at least partially, mediated by cyclic AMP, probably through an action on islet adenyl cyclase.

Cyclic AMP metabolism and lipolysis in cultured human adipocyte precursors

1980 ◽  
Vol 58 (3) ◽  
pp. 201-205 ◽  
Author(s):  
Daniel A. K. Roncari ◽  
Henry Wang ◽  
Kappu S. Desai
Keyword(s):  
Fatty Acids ◽  
Cyclic Amp ◽  
Cell Types ◽  
Phosphodiesterase Activity ◽  
Fat Cell ◽  
Triacylglycerol Lipase ◽  
Human Adipocyte ◽  
Cyclic Amp Phosphodiesterase ◽  
Early Stages ◽  
Adipocyte Precursor

Triacylglycerol breakdown (lipolysis) results from a series of reactions culminated by activation of "hormone-stimulated" triacylglycerol lipase, an enzyme unique to adipose tissue. We have studied various components of the lipolytic process in human omental adipocyte precursors differentiating in culture. The levels of cyclic AMP, the "second messenger" of lipolytic hormones, were about sixfold higher in fat cell precursors than those in abdominal skin fibroblasts. L-Isoproterenol resulted in significant elevation of cyclic AMP levels in both cell types. Preincubation of intact adipocyte precursors with insulin resulted in significant enhancement of "low Km" cyclic AMP phosphodiesterase activity; in contrast, this hormone had no effect on fibroblast phosphodiesterase activity, a distinctive biochemical difference despite the morphological similarities between the two cell types during the early stages of adipocyte precursor maturation. Incubation of adipocyte precursors with isoproterenol resulted in the release of fatty acids into the medium, findings indicative of "hormone-stimulated" lipase activity and, hence, the operation of the entire "lipolytic cascade"; isoproterenol-stimulated lipolysis was inhibited by insulin. Release of fatty acids from fibroblasts was not observed. Thus, "hormone-stimulated" lipolysis and insulin stimulation of cyclic AMP phosphodiesterase activity are expressed during early stages of human adipocyte precursor differentiation.

Effect of physical training on control mechanisms of lipolysis in rat fat cell ghosts

1977 ◽  
Vol 42 (6) ◽  
pp. 884-888 ◽  
Author(s):  
R. E. Shepherd ◽  
W. L. Sembrowich ◽  
H. E. Green ◽  
P. D. Gollnick
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Regulatory System ◽  
Plasma Free Fatty Acid ◽  
Female Rats ◽  
Supernatant Fraction ◽  
Protein Kinase Activity ◽  
Fat Cells ◽  
Control Mechanisms ◽  
Fat Cell

Fat cell ghosts and homogenates of fat cells were used to study the influence of training on the regulatory system for lipolysis in adipose tissue of female rats. A training effect was identified from elevated succinate dehydrogenase activities in the soleus and plantaris muscles. Neither basal nor maximal (NaF-stimulated) adenylate cyclase activities per mg protein of fat cell ghosts were altered by training. Fluoride-stimulated adenylate cyclase activity per microgram DNA was lower in the trained than untrained group. Adenylate cyclase activities in response to norepinephrine expressed either on a per mg protein or per microgram DNA basis were lower (P less than 0.05) in fat cell ghosts from trained rats. Phosphodiesterase activity was higher (P less than 0.05) in fat cell ghosts from trained rats for cyclic AMP concentrations of 1–-5.0 micrometer. The apparent Km's of phosphodiesterase were 1.19 and 2.0 micrometer of cyclic AMP for the untrained and trained groups, respectively (P less than 0.05). Protein kinase activity in the supernatant fraction of homogenates of fat cells was unchanged due to training. The overall effect of training was to blunt the system for cyclic AMP production in rat adipocytes. This may explain, at least partially, the lower plasma free fatty acid levels observed in trained compared to untrained persons during submaximal exercise.

scholarly journals An effect of insulin on adipose-tissue adenosine 3′:5′-cyclic monophosphate phosphodiesterase

1970 ◽  
Vol 120 (1) ◽  
pp. 187-193 ◽  
Author(s):  
E. G. Loten ◽  
J. G. T. Sneyd
Keyword(s):  
Adipose Tissue ◽  
Cyclic Amp ◽  
Cyclic Nucleotide ◽  
Fat Cells ◽  
Maximal Velocity ◽  
Isolated Fat Cells ◽  
Phosphodiesterase Activity ◽  
Cyclic Monophosphate ◽  
Cyclic Nucleotide Phosphodiesterases ◽  
Fat Pads

1. 3′:5′-Cyclic nucleotide phosphodiesterase activity was measured in homogenates prepared from epididymal fat-pads and isolated fat-cells incubated in the absence and presence of insulin. 2. Homogenates of insulin-treated tissues showed an increase in phosphodiesterase activity compared with controls. No effect of insulin was observed when the hormone was added directly to homogenates. 3. There was kinetic evidence for the presence of two 3′:5′-cyclic nucleotide phosphodiesterases in adipose tissue. Insulin raised the maximal velocity of the low-Km enzyme and lowered the Km of the higher-Km enzyme. 4. It is suggested that the effect of insulin on adipose tissue phosphodiesterase accounts for the ability of this hormone to lower cyclic-AMP concentration in the tissue.

On the Mechanism of Adenyl Cyclase Inhibition by Adenosine

1973 ◽  
Vol 51 (3) ◽  
pp. 190-196 ◽  
Author(s):  
S. G. McKenzie ◽  
H. P. Bär
Keyword(s):  
Cyclic Amp ◽  
Rat Brain ◽  
Inhibitory Action ◽  
Adenyl Cyclase ◽  
Physiological Significance ◽  
Fat Cells ◽  
Basal Activity ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Cells ◽  
Rat Fat Cells

Adenosine inhibited basal and fluoride- or hormone-stimulated adenyl cyclase activities from various sources. Inhibition was usually noted at 0.01 mM adenosine and was 40–75% at 1 mM. The effect appeared to be rapid and reversible, but it was not competitive with respect to ATP, as determined with enzyme from rat brain. Stimulated adenyl cyclase activities from rat fat cells and Ehrlich ascites cells were proportionately more inhibited than basal activity indicating the possibility of multiple sites for inhibitory action by adenosine. The effect of adenosine on adenyl cyclase and other enzymes of the cyclic AMP pathway may be of pharmacological or physiological significance in certain tissues.

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