Atrial natriuretic peptide (ANP) acts via specific binding sites on cGMP system of rat pancreatic islets without affecting insulin release.
Atrial natriuretic peptide (ANP) has been shown to increase plasma insulin levels in vivo and to act on various target cells as a potent stimulator of the cGMP system. It has, therefore, been investigated whether ANP has a direct insulinotropic effect mediated by specific binding sites and by affecting the cGMP system in isolated rat pancreatic islets. Unlabelled ANP inhibited 125I-ANP binding in a concentration-related manner (Kd1 and Kd2 = 0.02 and 11.2 nM, Bmax1 and Bmax2 = 0.0147 and 0.0328 pmoles per 1 mg protein). ANP was able to augment cGMP levels in islets, but was not able to enhance insulin secretion at various glucose concentrations. Since the role of cGMP for the glucose-mediated insulin release is controversial, in addition to ANP M&B 22,948 (a cGMP phosphodiesterase inhibitor) was investigated to evaluate the possible role of cGMP for insulin release more precisely. Like ANP M&B 22,948 increased cGMP levels but did not affect insulin release. The data indicate no direct insulinotropic effect of ANP, although ANP binding sites are present on rat pancreatic islets and question the claimed role of cGMP for insulin secretion in general. Therefore, the recently observed in vivo elevation of plasma insulin levels in response to ANP is rather an indirect than a direct effect.
Verspohl
E J
EJ
Department of Pharmacology, Institute of Pharmaceutical Science, Tübingen, Federal Republic of Germany.
Ammon
H P
HP
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007457:Iodine Radioisotopes; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D011688:Purinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*
D007328:Insulin; D007457:Iodine Radioisotopes; D010726:Phosphodiesterase Inhibitors; D011506:Proteins; D011688:Purinones; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C011145:zaprinast; D006152:Cyclic GMP; D005947:Glucose