Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulsatile administration of glucagon to perifused rat hepatocytes stimulates hepatocyte glucose production (HGP) more effectively than continuous administration. Having established that this effect was due to delayed relaxation of glucagon-stimulated HGP (t1/2 for decay = 3.54 +/- 0.60 min) we wished to examine the mechanism of response termination. Delayed dissociation of glucagon from its receptor was excluded by the brisk washout of [125I]glucagon from perifusion columns (t1/2 = 1.00 +/- 0.13) and the rapid decay in glucagon-stimulated cAMP released into the perifusion medium (t1/2 = 1.14 +/- 0.12). The relaxation of the HGP response to a pulse of administered cAMP was comparable to the decay in glucagon-stimulated HGP (t1/2 = 3.28 +/- 0.22). Furthermore, the phosphodiesterase inhibitor isobutyl-methylxanthine did not alter the decay of the HGP response to glucagon despite increasing the amplitude of the response (t1/2 = 3.04 +/- 0.36). These data place the rate-limiting step for HGP relaxation distal to cAMP generation and degradation. The decay of the beta-hydroxybutyrate response to a glucagon pulse was not different from the cAMP response (t1/2 = 1.14 +/- 0.23), whereas the decay of gluconeogenesis from lactate was not significantly different from HGP relaxation (t1/2 = 1.94 +/- 0.08). We conclude that rate-limiting events for HGP relaxation occur distal to the second messenger cascade; however, ketogenesis is more closely coupled to the kinetics of cAMP. These results may help to explain the absence of excessive ketosis during fasting in normal humans, who secrete glucagon episodically at 10- to 14-min intervals.
 ...
PMID:A kinetic analysis of hepatocyte responses to a glucagon pulse: mechanism and metabolic consequences of differences in response decay times. 243 20

Low-Michaelis constant cAMP phosphodiesterase (PDE; EC3.1.4.C) activity is inhibited in tissues of rats with type I ketosis-prone diabetes and is restored to normal by insulin treatment. To determine whether the oral hypoglycemic agent glyburide affected tissue cAMP PDE activity in non-insulin-dependent oral agent-treatable diabetes, cAMP PDE activity was measured in the liver and fat of animals rendered diabetic by low-dose streptozocin (STZ-DM) and treated for 3 wk with oral glyburide (360 micrograms/kg). The results were compared with PDE activity in the liver and fat of untreated STZ-DM and normal control rats. At the time of death, low-Km cAMP PDE activity [as maximum velocity (Vmax)] in STZ-DM rats was decreased to 66% of control values in the liver and to 65% in fat (P less than .001). PDE activity was restored toward normal by glyburide treatment: 91% in the liver (P less than .01) and 80% in fat (P less than .05). Calmodulin and calmodulin-like activity (PDE-activator activity) in the liver and fat was decreased in diabetes and restored toward normal after glyburide treatment (P less than .05). These data demonstrate that oral agents as well as insulin can restore the activity of cAMP PDE in the low-dose STZ-DM model, which is in some ways similar to type II diabetes.
 ...
PMID:Cyclic AMP phosphodiesterase in diabetes. Effect of glyburide. 301 8