Signal transduction in islet hormone release: interaction of nitric oxide with basal and nutrient-induced hormone responses.
We examined the relation between the islet NO system and islet hormone secretion induced by either the non-glucose nutrient alpha-ketoisocaproic acid (KIC) or, in some experiments, glucose. KIC dose dependently stimulated insulin but inhibited glucagon secretion. In a medium devoid of any nutrient, the NO synthase (NOS)-inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) induced an increase in basal insulin release but a decrease in glucagon release. These effects were evident also in K+-depolarised islets. KIC-induced insulin release was increased by L-NAME. This increase was abolished in K+-depolarised islets. In contrast, glucose- induced insulin release was potentiated by L-NAME after K+ depolarisation. The intracellular NO donor hydroxylamine dose dependently inhibited KIC-stimulated insulin release and reversed KIC-induced suppression of glucagon release. Our data suggest that islet hormone secretion in a medium devoid of nutrients is greatly affected by the islet NO system, whereas KIC-induced secretion is little affected. Glucose-induced insulin release, however, is accompanied by increased NOS activity, the NOS-activating signal being derived from the glycolytic-pentose shunt part of glucose metabolism. The observed NO effects on islet hormone release can proceed independently of membrane-depolarisation events.
Salehi
A
A
Department of Pharmacology, University of Lund, Sweden. salehi@farm.lu.se
Parandeh
F
F
Lundquist
I
I
D000818:Animals; D002208:Caproates / Q000008:administration & dosage / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D019811:Hydroxylamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D002208:Caproates; D004791:Enzyme Inhibitors; D007328:Insulin; D020030:Nitric Oxide Donors; C001916:alpha-ketocaproic acid; D019811:Hydroxylamine; D009569:Nitric Oxide; D005934:Glucagon; D019001:Nitric Oxide Synthase; D005947:Glucose; D003981:Diazoxide; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester