Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin secreting cell Line BRIN-BD11

M Ahmad, Yasser Abdel-Wahab, R Tate, Peter Flatt, NJ Pyne, BL Furman

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Abstract

1 The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN-BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT-PCR. 2 Calmodulin activated cyclic AMP or cyclic GMP PDE. activity in pellet and was 3 fold (P=0.002) more potent in activating cyclic nucleotide hydrolysis in pellet compared with supernatant fractions. 3 The PDE1/PDE5 inhibitor zaprinast inhibited both cyclic AMP and cyclic GMP PDE activity in both pellet and supernatant fractions of cell homogenates by a maximum of around 25% (IC50 1-5 mu M), while rolipram (PDE4 selective) inhibited only cyclic AMP hydrolysis. 4 The PDE3-selective inhibitors Org 9935 (0.02-10 mu M) and siguazodan (0.1-10 mu M) inhibited cyclic AMP PDE activity in the: pellet but not the supernatant fractions of cell homogenates, with a maximum inhibition of about 30%. IGF-1 (2-7.5 ng ml(-1)) potently augmented this PDE activity. 5 RT-PCR using specific primers for PDE3B, but nor for PDE3A, amplified, From BRIN-BD11 cell total RNA, a 351 base pair product that was >97% homologous with rat adipose tissue PDE3B. 6 IBMX, Org 9935, siguazodan and rolipram (1-50 mu M), but not zaprinast, each augmented glucose-induced insulin secretion in the presence of 16.7 mM but not 1 mM glucose. 7 These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the pool of cyclic AMP relevant to the modulation of glucose-induced insulin secretion.
LanguageEnglish
Pages1228-1234
JournalBritish Journal of Pharmacology
Volume129
Issue number6
Publication statusPublished - Mar 2000

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Cyclic Nucleotides
Phosphoric Diester Hydrolases
Insulin-Secreting Cells
Cyclic AMP
Insulin
Cell Line
Rolipram
Cyclic GMP
Calmodulin
Insulin-Like Growth Factor I
Glucose
Hydrolysis
Phosphodiesterase 3 Inhibitors
Phosphodiesterase 5 Inhibitors
1-Methyl-3-isobutylxanthine
Polymerase Chain Reaction
Insulin-Like Growth Factor II
Phosphodiesterase Inhibitors
Base Pairing
Isoenzymes

Cite this

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title = "Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin secreting cell Line BRIN-BD11",
abstract = "1 The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN-BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT-PCR. 2 Calmodulin activated cyclic AMP or cyclic GMP PDE. activity in pellet and was 3 fold (P=0.002) more potent in activating cyclic nucleotide hydrolysis in pellet compared with supernatant fractions. 3 The PDE1/PDE5 inhibitor zaprinast inhibited both cyclic AMP and cyclic GMP PDE activity in both pellet and supernatant fractions of cell homogenates by a maximum of around 25{\%} (IC50 1-5 mu M), while rolipram (PDE4 selective) inhibited only cyclic AMP hydrolysis. 4 The PDE3-selective inhibitors Org 9935 (0.02-10 mu M) and siguazodan (0.1-10 mu M) inhibited cyclic AMP PDE activity in the: pellet but not the supernatant fractions of cell homogenates, with a maximum inhibition of about 30{\%}. IGF-1 (2-7.5 ng ml(-1)) potently augmented this PDE activity. 5 RT-PCR using specific primers for PDE3B, but nor for PDE3A, amplified, From BRIN-BD11 cell total RNA, a 351 base pair product that was >97{\%} homologous with rat adipose tissue PDE3B. 6 IBMX, Org 9935, siguazodan and rolipram (1-50 mu M), but not zaprinast, each augmented glucose-induced insulin secretion in the presence of 16.7 mM but not 1 mM glucose. 7 These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the pool of cyclic AMP relevant to the modulation of glucose-induced insulin secretion.",
author = "M Ahmad and Yasser Abdel-Wahab and R Tate and Peter Flatt and NJ Pyne and BL Furman",
year = "2000",
month = "3",
language = "English",
volume = "129",
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journal = "British Journal of Pharmacology",
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TY - JOUR

T1 - Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin secreting cell Line BRIN-BD11

AU - Ahmad, M

AU - Abdel-Wahab, Yasser

AU - Tate, R

AU - Flatt, Peter

AU - Pyne, NJ

AU - Furman, BL

PY - 2000/3

Y1 - 2000/3

N2 - 1 The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN-BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT-PCR. 2 Calmodulin activated cyclic AMP or cyclic GMP PDE. activity in pellet and was 3 fold (P=0.002) more potent in activating cyclic nucleotide hydrolysis in pellet compared with supernatant fractions. 3 The PDE1/PDE5 inhibitor zaprinast inhibited both cyclic AMP and cyclic GMP PDE activity in both pellet and supernatant fractions of cell homogenates by a maximum of around 25% (IC50 1-5 mu M), while rolipram (PDE4 selective) inhibited only cyclic AMP hydrolysis. 4 The PDE3-selective inhibitors Org 9935 (0.02-10 mu M) and siguazodan (0.1-10 mu M) inhibited cyclic AMP PDE activity in the: pellet but not the supernatant fractions of cell homogenates, with a maximum inhibition of about 30%. IGF-1 (2-7.5 ng ml(-1)) potently augmented this PDE activity. 5 RT-PCR using specific primers for PDE3B, but nor for PDE3A, amplified, From BRIN-BD11 cell total RNA, a 351 base pair product that was >97% homologous with rat adipose tissue PDE3B. 6 IBMX, Org 9935, siguazodan and rolipram (1-50 mu M), but not zaprinast, each augmented glucose-induced insulin secretion in the presence of 16.7 mM but not 1 mM glucose. 7 These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the pool of cyclic AMP relevant to the modulation of glucose-induced insulin secretion.

AB - 1 The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN-BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT-PCR. 2 Calmodulin activated cyclic AMP or cyclic GMP PDE. activity in pellet and was 3 fold (P=0.002) more potent in activating cyclic nucleotide hydrolysis in pellet compared with supernatant fractions. 3 The PDE1/PDE5 inhibitor zaprinast inhibited both cyclic AMP and cyclic GMP PDE activity in both pellet and supernatant fractions of cell homogenates by a maximum of around 25% (IC50 1-5 mu M), while rolipram (PDE4 selective) inhibited only cyclic AMP hydrolysis. 4 The PDE3-selective inhibitors Org 9935 (0.02-10 mu M) and siguazodan (0.1-10 mu M) inhibited cyclic AMP PDE activity in the: pellet but not the supernatant fractions of cell homogenates, with a maximum inhibition of about 30%. IGF-1 (2-7.5 ng ml(-1)) potently augmented this PDE activity. 5 RT-PCR using specific primers for PDE3B, but nor for PDE3A, amplified, From BRIN-BD11 cell total RNA, a 351 base pair product that was >97% homologous with rat adipose tissue PDE3B. 6 IBMX, Org 9935, siguazodan and rolipram (1-50 mu M), but not zaprinast, each augmented glucose-induced insulin secretion in the presence of 16.7 mM but not 1 mM glucose. 7 These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the pool of cyclic AMP relevant to the modulation of glucose-induced insulin secretion.

M3 - Article

VL - 129

SP - 1228

EP - 1234

JO - British Journal of Pharmacology

T2 - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

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ER -