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.

LIPOLYSIS AND ADENOSINE 3′,5′-CYCLIC MONOPHOSPHATE IN ADIPOSE TISSUE OF THE NEW ZEALAND OBESE MOUSE

1973 ◽  
Vol 56 (1) ◽  
pp. 1-11 ◽  
Author(s):  
C. J. LOVELL-SMITH ◽  
J. G. T. SNEYD
Keyword(s):  
Adipose Tissue ◽  
New Zealand ◽  
Obese Mouse ◽  
Fat Cells ◽  
Obese Mice ◽  
Isolated Fat Cells ◽  
Glycerol Release ◽  
Cyclic Monophosphate ◽  
New Zealand Obese Mouse

SUMMARY Isolated fat cells from young New Zealand obese mice (NZO/Bl) showed an impaired rate of glycerol release in response to isoprenaline. Old animals showed an increased rate of glycerol release. The impaired lipolysis in young animals may be caused by failure of the adenosine 3′,5′-cyclic monophosphate level to rise normally when isolated fat cells are treated with isoprenaline. It is proposed that the impaired lipolysis in young NZO/Bl mice is important in the development of obesity.

scholarly journals Theoretical analysis of the consequences of cyclic nucleotide phosphodiesterase negative co-operativity. Amplification and positive co-operativity of cyclic AMP accumulation

1980 ◽  
Vol 192 (1) ◽  
pp. 241-246 ◽  
Author(s):  
C Erneux ◽  
J M Boeynaems ◽  
J E Dumont
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclic Nucleotide ◽  
Slight Variation ◽  
Maximal Velocity ◽  
Cyclic Nucleotide Phosphodiesterases ◽  
Accumulation Curve ◽  
Cyclic Amp Accumulation ◽  
Stimulation Of ◽  
Nucleotide Phosphodiesterases

Most tissues contain multiple forms of cyclic nucleotide phosphodiesterases (3′:5′-cyclic-nucleotide 5′ nucleotidohydrolase, EC 3.1.4.17). Consequently, in most, if not in all, tissues, substrate-velocity curves deviate from Michaelian kinetics and exhibit an apparent negative co-operativity. We have studied the possible theoretical consequences of this property on the quantitative features of cyclic AMP accumulation in response to activation of adenylate cyclase. Negative co-operativity of phosphodiesterases tends to generate a “positively co-operative” cyclic AMP accumulation curve. It amplifies the stimulation of cyclic AMP accumulation as compared with the stimulation of cyclic AMP synthesis. It enhances the sensitivity of cyclic AMP accumulation to slight variation of phosphodiesterase maximal velocity. It tends to shift the cyclic AMP accumulation curve to higher concentrations of stimulator as compared with the adenylate cyclase activation curve. This accounts for much of the data in the literature of hormonal effects on phosphodiesterase activity. It shows that the characteristics of cyclic nucleotide phosphodiesterases are as important as those of adenylate cyclase in determining the response of the system.

scholarly journals Evidence that insulin activates casein kinase 2 in rat epididymal fat-cells and that this may result in the increased phosphorylation of an acid-soluble 22 kDa protein

1991 ◽  
Vol 279 (2) ◽  
pp. 545-551 ◽  
Author(s):  
T A Diggle ◽  
C Schmitz-Peiffer ◽  
A C Borthwick ◽  
G I Welsh ◽  
R M Denton
Keyword(s):  
Adipose Tissue ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Fat Cells ◽  
Isolated Fat Cells ◽  
Peptide Substrate ◽  
Heat Stable ◽  
Epididymal Fat ◽  
Rat Adipose Tissue ◽  
Fat Pads

Casein kinase 2 activity as measured by phosphorylation of the peptide substrate Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu is increased by about 50% in extracts from insulin-treated epididymal fat-pads or isolated fat-cells after purification by Mono Q chromatography. Insulin acts to increase the Vmax. of the kinase. An acid-soluble protein with an apparent subunit molecular mass of about 22 kDa appears to be a substrate for casein kinase 2. The protein possesses a number of properties in common with the acid-soluble heat-stable 22 kDa protein which exhibits increased phosphorylation in rat adipose tissue exposed to insulin.

scholarly journals Specific antibodies and the selective inhibitor ICI 118233 demonstrate that the hormonally stimulated ‘dense-vesicle’ and peripheral-plasma-membrane cyclic AMP phosphodiesterases display distinct tissue distributions in the rat

1987 ◽  
Vol 248 (3) ◽  
pp. 897-901 ◽  
Author(s):  
N J Pyne ◽  
N Anderson ◽  
B E Lavan ◽  
G Milligan ◽  
H G Nimmo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Plasma Membrane ◽  
Cyclic Amp ◽  
Rat Liver ◽  
White Adipose Tissue ◽  
Tissue Homogenate ◽  
Phosphodiesterase Activity ◽  
Cyclic Amp Phosphodiesterase ◽  
Peripheral Plasma ◽  
Membrane Enzyme

Polyclonal-antibody preparations DV1 and PM1, raised against purified preparations of rat liver insulin-stimulated ‘dense-vesicle’ and peripheral-plasma-membrane cyclic AMP phosphodiesterases, were used to analyse rat liver homogenates by Western-blotting techniques. The antibody DV1 identified only the 63 kDa native subunit of the ‘dense-vesicle’ enzyme, and the antibody PM1 only the 52 kDa subunit of the plasma-membrane enzyme. These antibodies also detected the subunits of these two enzymes in homogenates of kidney, heart and white adipose tissue from rat. Quantitative immunoblotting demonstrated that the amount of these enzymes (by wt.) varied in these different tissues, as did the expression of these two enzymes, relative to each other, by a factor of as much as 7-fold. The ratio of the dense-vesicle enzyme to the peripheral-plasma-membrane enzyme was lowest in liver and kidney and highest in heart and white adipose tissue. ICI 118233 was shown to inhibit selectively the ‘dense-vesicle’ cyclic AMP phosphodiesterase in liver. It did this in a competitive fashion, with a Ki value of 3.5 microM. Inhibition of tissue-homogenate cyclic AMP phosphodiesterase activity by ICI 118233 was used as an index of the contribution to activity by the ‘dense-vesicle’ enzyme. By this method, a tissue distribution of the ‘dense-vesicle’ enzyme was obtained which was similar to that found by using the immunoblotting technique. The differential expression of isoenzymes of cyclic AMP phosphodiesterase activity in various tissues might reflect a functional adaptation, and may provide the basis for the different physiological actions of compounds which act as selective inhibitors.

Synthesis and vectorial export of cGMP in airway epithelium: expression of soluble and CNP-specific guanylate cyclases

1993 ◽  
Vol 265 (6) ◽  
pp. L598-L605 ◽  
Author(s):  
C. A. Geary ◽  
M. F. Goy ◽  
R. C. Boucher
Keyword(s):  
Natriuretic Peptide ◽  
Guanylate Cyclase ◽  
Cyclic Nucleotide ◽  
Soluble Guanylate Cyclase ◽  
Basolateral Membrane ◽  
Primary Cultures ◽  
Respiratory Epithelium ◽  
Maximal Velocity ◽  
Lower Efficiency ◽  
Cyclic Monophosphate

Guanosine 5'-cyclic monophosphate (cGMP) is an important modulator of fluid balance in many epithelia. We examined its metabolism in primary cultures of human airway epithelia. Sodium nitroprusside increased cGMP levels 30-fold, suggesting that the respiratory epithelium expresses a soluble guanylate cyclase; however, endogenous nitric oxide production was not detected. cGMP levels could also be increased by C-type natriuretic peptide (CNP), but not by atrial natriuretic peptide, brain natriuretic peptide, or Escherichia coli heat-stable enterotoxin, indicating expression of a CNP-specific membrane-bound guanylate cyclase. The one-half effective concentration for CNP was 40 nM and the maximal velocity was 56.7 pmol cGMP.mg protein-1.h-1. After CNP stimulation, approximately 60% of the total synthesized cGMP was preferentially exported from the polarized epithelial cells across the basolateral membrane by a probenecid-sensitive process. Isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) export revealed a similar export pattern and probenecid sensitivity, although a lower efficiency of export (27% of total cAMP was exported). Consistent with previous reports, export of neither cyclic nucleotide was saturable at the concentrations tested. We conclude that the respiratory epithelium expresses a soluble guanylate cyclase, a CNP-specific receptor, and a novel vectorial cyclic nucleotide export mechanism.

Distribution of cyclic AMP phosphodiesterase in adipose tissue from trained rats

1986 ◽  
Vol 61 (4) ◽  
pp. 1546-1551 ◽  
Author(s):  
K. A. Kenno ◽  
J. L. Durstine ◽  
R. E. Shepherd
Keyword(s):  
Cyclic Amp ◽  
Specific Activity ◽  
Particulate Fraction ◽  
Fat Cells ◽  
Isolated Fat Cells ◽  
Sprague Dawley ◽  
Enzyme Form ◽  
Cyclic Amp Phosphodiesterase ◽  
Sprague Dawley Rats ◽  
Michaelis Constants

Fat cells were isolated from sedentary and exercise trained female Sprague-Dawley rats and cyclic AMP phosphodiesterase (cyclic AMP-PDE) activities were determined from crude homogenates of the fat cells in the whole homogenate, P5, P48, and S48 fractions. Exercise training resulted in a significant increase in the mean specific activity of cyclic AMP-PDE (pmol X min-1 X mg-1) from the whole homogenate and S48 fraction at cyclic AMP concentrations of 4, 8, and 16 microM and in the P48 fraction at 8 and 16 microM cyclic AMP. Cyclic AMP-PDE kinetic plots according to Lineweaver-Burk for the calculation of Michaelis constants (Km) and maximum enzyme velocities (Vmax) were nonlinear, indicating both a low and high enzyme form. The Michaelis constants were significantly lower in trained rats than those of its control for the high Km form of cyclic AMP-PDE in the whole and soluble fractions and for the low Km form of the P5 particulate fraction. The Vmax of the high Km form of the P48 particulate fraction from trained animals was also significantly higher than that found in its control. Phosphodiesterase inhibition by methylxanthines in the various fractions was similar in both trained and sedentary animals. These changes in specific activity, Michaelis constants, and Vmax of cyclic AMP-PDE from crude homogenates of isolated fat cells from exercise trained animals may account for the decreased intracellular levels of cyclic AMP following catecholamine stimulation of isolated fat cells from trained rats.

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