Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 685, Issue 1-3, Pages 213-217Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2012.04.005
Keywords
Insulin secretion; Irsogladine; MIN6 cell; Gap junction; Connexin 36; cAMP
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Funding
- Grants-in-Aid for Scientific Research [23390185] Funding Source: KAKEN
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Insulin secretion by pancreatic islets is a multicellular process. In addition to other essential systems, gap junctions are an important component of cell-to-cell communication in pancreatic islets. It is well known that dysfunction of gap junctions causes inappropriate insulin secretion. The anti-ulcer agent, irsogladine, increases gap junctions in some cell types. To examine the effect of irsogladine on insulin secretion, we investigated insulin secretion by MIN6 cells treated with or without irsogladine. The expression of connexin 36 proteins and intracellular cAMP levels were also determined using immunoblotting and ELISA assays, respectively. Irsogladine had no effect on insulin secretion under 5.6 mM glucose conditions. However, under 16.7 mM glucose conditions, irsogladine (1.0 x 10(-5) M) induced a 1.7 +/- 0.20 fold increase in insulin secretion compared to the control (P<0.05). This effect of irsogladine on insulin secretion was inhibited by the addition of the gap junction inhibitor 18-beta-glycyrrhetinic acid. Irsogladine treatment increased the protein level of connexin 36 in the plasma membrane fraction. The intracellular cAMP level in MIN6 cells was significantly, but mildly, increased by irsogladine treatment. Furthermore, Rp-cAMP and H89 inhibited the effects of irsogladine on insulin secretion under high glucose conditions. Irsogladine increases insulin secretion under high glucose conditions. The up-regulation of gap junction channels and the increased level of intracellular cAMP induced by irsogladine treatment suggest that these phenomena are involved in irsogladine-induced increased insulin secretion. (C) 2012 Elsevier B. V. All rights reserved.
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