Interleukin-1 beta effects on cyclic GMP and cyclic AMP in cultured rat islets of Langerhans-arginine-dependence and relationship to insulin secretion.
When islets were cultured with interleukin-1 beta (1 or 100 pmol/l) for 12 h in arginine-containing medium, cyclic GMP levels were increased 1.6- and 4.5-fold respectively. The arginine analogue, N-omega-nitro-L-arginine methyl ester, which blocks nitric oxide formation and partially reverses inhibition of insulin secretion by 100 pmol/l interleukin-1 beta, largely, but not completely, blocked generation of cyclic GMP. Treatment of islets with 100 pmol/l interleukin-1 beta for 12 h significantly decreased islet cyclic AMP generation in the absence of isobutylmethylxanthine (from 13.1 +/- 0.7 to 9.3 +/- 0.8 fmol/micrograms islet protein), this fall was arginine-dependent and may have resulted from an effect on a cyclic AMP phosphodiesterase, since it was masked if isobutylmethylxanthine was present. Isobutylmethylxanthine (0.4 mmol/l) reduced the inhibitory potency of interleukin-1 beta in 15 h slightly but significantly from 80.5 to 59.0%. The morpholinosydnonimine SIN-1, which is a nitric oxide donor, inhibited insulin secretion, raised islet cyclic GMP and lowered cyclic AMP; its effects were similar to those of interleukin-1 beta. However, 6-anilinoquinoline-5,8-quinone, [LY83583 (1-10 mumol/l)], inhibited insulin secretion, and significantly decreased cyclic GMP while 8-bromocyclic GMP stimulated insulin secretion. Both low- and high-dose interleukin-1 beta treatment give a large arginine-dependent and a small, yet significant, arginine-independent increase in cyclic GMP. The inhibitory effect of SIN-1 or interleukin-1 beta on insulin secretion seems to depend to a small extent on decreased islet cyclic AMP, though sustained increases in nitric oxide or depleted islet GTP may directly affect the secretory process.
Green
I C
IC
Biochemistry Laboratory, School of Biological Sciences University of Sussex, Brighton, UK.
Delaney
C A
CA
Cunningham
J M
JM
Karmiris
V
V
Southern
C
C
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D017207:Rats, Sprague-Dawley
D000634:Aminoquinolines; D000959:Antihypertensive Agents; D007328:Insulin; D007375:Interleukin-1; D005576:Colforsin; C002385:linsidomine; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D008981:Molsidomine; D000242:Cyclic AMP; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine; D019331:NG-Nitroarginine Methyl Ester