Effects of the new phosphodiesterase inhibitor griseolic acid on insulin release in rat pancreatic islets.
A new cyclic AMP phosphodiesterase inhibitor, griseolic acid (CAS 79030-08-3), in a dose-dependent manner increased insulin release and cyclic AMP level in rat pancreatic islets in the presence of 5.5 mmol/l glucose. Griseolic acid (0.26 mmol/l) or 3-isobutyl-1-methylxanthine (IBMX) (1 mmol/l) enhanced insulin release and cyclic AMP level both in the presence of 5.5 and 16.7 mmol/l glucose (no significant difference). In perifusion system, 45Ca++ efflux and insulin release showed a monophasic increase when the islets were exposed to 1.3 mmol/l griseolic acid or 1 mmol/l IBMX in the presence of 5.5 mmol/l glucose (no significant difference). In a cell-free system, griseolic acid had a stronger inhibitory effect on cyclic AMP phosphodiesterase activity than IBMX, has a stimulatory effect on insulin release through an increase of cyclic AMP by inhibiting phosphodiesterase in pancreatic islets, but it might not cross the plasma membrane easily.
Hashimoto
N
N
Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
Makino
H
H
Kanatsuka
A
A
Yamazaki
M
M
Yoshida
S
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002132:Calcium Radioisotopes; D007328:Insulin; C046499:griseolic acid; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000241:Adenosine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine