Role of adenine nucleotides in insulin secretion from MIN6 pseudoislets

Mol Cell Endocrinol. 2002 Jun 14;191(2):167-76. doi: 10.1016/s0303-7207(02)00051-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides / metabolism
  • Adenine Nucleotides / pharmacology
  • Adenine Nucleotides / physiology*
  • Animals
  • Autocrine Communication
  • Calcium / metabolism
  • Cell Line
  • Glucokinase / analysis
  • Glucose / pharmacology
  • Glucose Transporter Type 2
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Mice
  • Monosaccharide Transport Proteins / analysis
  • Paracrine Communication


  • Adenine Nucleotides
  • Glucose Transporter Type 2
  • Insulin
  • Monosaccharide Transport Proteins
  • Glucokinase
  • Glucose
  • Calcium