title: Role of adenine nucleotides in insulin secretion from MIN6 pseudoislets.
abstract: Insulin secretion from MIN6 cells configured as cell aggregates by culture on a gelatin substrate (pseudoislets) is enhanced compared to that of MIN6 cells grown as monolayers on tissue culture plastic, indicating the importance of beta-cell-to-beta-cell proximity for insulin release. In this study we have shown that glucose induced a biphasic release of insulin from pseudoislets, whereas the amplitude and duration of the responses of equivalent monolayer cells were much reduced. Purinergic aqonists have been implicated in intercellular communication between beta-cells, so we investigated whether adenine nucleotides co-released with insulin are responsible for the enhanced secretory responses of pseudoislets. We have demonstrated that MIN6 cells express purinergic A(1) and P2Y receptors, and that adenine nucleotides increased [Ca(2+)](i) with an efficacy of agonists being ATP > ADP > AMP. However, neither suramin nor the more selective A(1) antagonist 1,3-dipropyl-8-cyclopentylxanthine reduced glucose-induced insulin secretion from pseudoislets, and stimulation of monolayer cells with a range of adenine nucleotides did not enhance glucose-induced secretion. These results suggest that enhanced secretion from MIN6 pseudoislets is not due to increased paracrine/autocrine action of adenine nucleotides.
authors.affiliation: Endocrinology and Reproduction Research Group, Biomedical Sciences, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Hauge-Evans
authors.forename: P E
authors.initials: PE
authors.lastname: Squires
authors.forename: V D
authors.initials: VD
authors.lastname: Belin
authors.forename: H
authors.initials: H
authors.lastname: Roderigo-Milne
authors.forename: R D
authors.initials: RD
authors.lastname: Ramracheya
authors.forename: S J
authors.initials: SJ
authors.lastname: Persaud
authors.forename: P M
authors.initials: PM
authors.lastname: Jones
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D019898:Autocrine Communication; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005941:Glucokinase / Q000032:analysis; D005947:Glucose / Q000494:pharmacology; D051273:Glucose Transporter Type 2; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D019899:Paracrine Communication
chemical_list: D000227:Adenine Nucleotides; D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D005941:Glucokinase; D005947:Glucose; D002118:Calcium