title: Interaction between cAMP, volume‑regulated anion channels and the Na+‑HCO3‑‑cotransporter, NBCe1, in the regulation of nutrient‑ and hypotonicity‑induced insulin release from isolated rat pancreatic islets and tumoral insulin‑producing BRIN‑BD11 cells.
abstract: Soluble adenylyl cyclase (sAC) has been hypothesized to play a role in insulin secretion. The present study aimed to investigate the interaction between adenosine 3',5'‑cyclic monophosphate (cAMP), volume‑regulated anion channels (VRACs) and the electrogenic sodium bicarbonate (Na+‑HCO3‑) cotransporter, NBCe1, in the regulation of nutrient‑ and hypotonicity‑induced insulin release from rat pancreatic islets and tumoral insulin‑producing BRIN‑BD11 cells. In the islets, 5‑nitro‑2‑(3‑phenylpropylamino)benzoic acid (NPPB) and 5‑chloro‑2‑hydroxy‑3‑(thiophene‑2‑carbonyl)indole‑1‑carboxamide (tenidap) reduced glucose‑stimulated insulin release, however, only NPPB suppressed the enhancing action of cAMP analogs upon such a release. Insulin output from the BRIN‑BD11 cells was stimulated by 2‑ketoisocaproate (KIC) or extracellular hypoosmolarity. cAMP analogs and 3‑isobutyl‑1‑methylxanthine increased the insulin output recorded in the isotonic medium to a greater relative extent than that in the hypotonic medium. The secretory response to KIC or hypotonicity was inhibited by NPPB or tenidap, which both also opposed the enhancing action of cAMP analogs. Inhibitors of mitogen‑activated protein (MAP) kinase decreased insulin output in isotonic and hypotonic media. The inhibitor of sAC, 2‑hydroxyestriol, caused only a modest inhibition of insulin release, whether in the isotonic or hypotonic medium, even when tested at a concentration of 100 µM. The omission of NaHCO3 markedly decreased the secretory response to KIC or extracellular hypotonicity. The omission of Na+ suppressed the secretory response to extracellular hypotonicity. The observations of the present study do not support the hypothesis of a major role for sAC in the regulation of insulin release.
authors: Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels B‑1070, Belgium.
authors: Nurdan
authors: N
authors: Bulur
authors: Raphael
authors: R
authors: Crutzen
authors: Willy J
authors: WJ
authors: Malaisse
authors: Abdullah
authors: A
authors: Sener
authors: Renaud
authors: R
authors: Beauwens
authors: Philippe
authors: P
authors: Golstein
mesh_terms: D000818:Animals; D000838:Anions; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism*; D004964:Estriol / Q000031:analogs & derivatives / Q000494:pharmacology; D005502:Food; D005947:Glucose / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism*; D000078790:Insulin Secretion; D007473:Ion Channels / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007552:Isotonic Solutions / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009579:Nitrobenzoates / Q000494:pharmacology; D000078183:Oxindoles; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D012015:Reference Standards; D012964:Sodium / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism*
chemical_list: D000838:Anions; D007038:Hypotonic Solutions; D007211:Indoles; D007328:Insulin; D007473:Ion Channels; D007552:Isotonic Solutions; D009579:Nitrobenzoates; D000078183:Oxindoles; D010726:Phosphodiesterase Inhibitors; D047428:Protein Kinase Inhibitors; C422004:Slc4a4 protein, rat; D027982:Sodium-Bicarbonate Symporters; C008012:2-hydroxyestriol; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C062866:tenidap; D012964:Sodium; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; D004964:Estriol; D005947:Glucose