Dual effect of ATP on glucose-induced insulin secretion in HIT-T15 cells

Dong Hyeon Lee, Kyusang Park, Dae Ran Kim, Joong Woo Lee, Indeok Kong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

OBJECTIVES:: The study investigated the dual effect of purinergic nucleotides on the secretion of insulin from pancreatic β cells. METHODS:: The level of insulin secretion in HIT-T15 cells of static incubation was measured using a radioimmunoassay. RESULTS:: The adenine nucleotides reduced the level of glucose-induced insulin secretion in a concentration-dependent manner, and the relative potency order (IC50; μM) was BzATP (6.9) > ATP (20.4) ≥ α, β-methylene ATP (23.3) ≥ 2-methylthio-ATP (24.9). Suramin and PPADS (200 μM), which are blockers of the purinergic receptors, had a little influence on the activity of ATP. However, the inhibitory effect of ATP was reversed by preincubation with oxidized ATP (200 μM), which is a P2X7 antagonist. The level of insulin secretion in these preincubated cells exposed to the purinergic nucleotides increased in the following order: ATP > α, β-methylene ATP ≥ 2-methylthio-ATP. A pretreatment with foskolin and PDBu (100 nM) potentiated the increasing effect of ATP on insulin secretion. The Western blotting showed the expression of P2X7 and P2Y11 receptors. CONCLUSIONS:: Purinergic stimulation has inhibitory activity on glucose-dependent insulin secretion through the activation of the P2X7 receptor, whereas it has enhancing effect through the activation of the P2Y11 receptor in HIT-T15 cells.

Original languageEnglish
Pages (from-to)302-308
Number of pages7
JournalPancreas
Volume37
Issue number3
DOIs
Publication statusPublished - 2008 Oct 1

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Adenosine Triphosphate
Insulin
Glucose
Purinergic P2X7 Receptors
Nucleotides
Purinergic Receptors
Suramin
Adenine Nucleotides
Inhibitory Concentration 50
Radioimmunoassay
Western Blotting
2-methylthio-ATP

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Lee, Dong Hyeon ; Park, Kyusang ; Kim, Dae Ran ; Lee, Joong Woo ; Kong, Indeok. / Dual effect of ATP on glucose-induced insulin secretion in HIT-T15 cells. In: Pancreas. 2008 ; Vol. 37, No. 3. pp. 302-308.
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Dual effect of ATP on glucose-induced insulin secretion in HIT-T15 cells. / Lee, Dong Hyeon; Park, Kyusang; Kim, Dae Ran; Lee, Joong Woo; Kong, Indeok.

In: Pancreas, Vol. 37, No. 3, 01.10.2008, p. 302-308.

Research output: Contribution to journalArticle

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N2 - OBJECTIVES:: The study investigated the dual effect of purinergic nucleotides on the secretion of insulin from pancreatic β cells. METHODS:: The level of insulin secretion in HIT-T15 cells of static incubation was measured using a radioimmunoassay. RESULTS:: The adenine nucleotides reduced the level of glucose-induced insulin secretion in a concentration-dependent manner, and the relative potency order (IC50; μM) was BzATP (6.9) > ATP (20.4) ≥ α, β-methylene ATP (23.3) ≥ 2-methylthio-ATP (24.9). Suramin and PPADS (200 μM), which are blockers of the purinergic receptors, had a little influence on the activity of ATP. However, the inhibitory effect of ATP was reversed by preincubation with oxidized ATP (200 μM), which is a P2X7 antagonist. The level of insulin secretion in these preincubated cells exposed to the purinergic nucleotides increased in the following order: ATP > α, β-methylene ATP ≥ 2-methylthio-ATP. A pretreatment with foskolin and PDBu (100 nM) potentiated the increasing effect of ATP on insulin secretion. The Western blotting showed the expression of P2X7 and P2Y11 receptors. CONCLUSIONS:: Purinergic stimulation has inhibitory activity on glucose-dependent insulin secretion through the activation of the P2X7 receptor, whereas it has enhancing effect through the activation of the P2Y11 receptor in HIT-T15 cells.

AB - OBJECTIVES:: The study investigated the dual effect of purinergic nucleotides on the secretion of insulin from pancreatic β cells. METHODS:: The level of insulin secretion in HIT-T15 cells of static incubation was measured using a radioimmunoassay. RESULTS:: The adenine nucleotides reduced the level of glucose-induced insulin secretion in a concentration-dependent manner, and the relative potency order (IC50; μM) was BzATP (6.9) > ATP (20.4) ≥ α, β-methylene ATP (23.3) ≥ 2-methylthio-ATP (24.9). Suramin and PPADS (200 μM), which are blockers of the purinergic receptors, had a little influence on the activity of ATP. However, the inhibitory effect of ATP was reversed by preincubation with oxidized ATP (200 μM), which is a P2X7 antagonist. The level of insulin secretion in these preincubated cells exposed to the purinergic nucleotides increased in the following order: ATP > α, β-methylene ATP ≥ 2-methylthio-ATP. A pretreatment with foskolin and PDBu (100 nM) potentiated the increasing effect of ATP on insulin secretion. The Western blotting showed the expression of P2X7 and P2Y11 receptors. CONCLUSIONS:: Purinergic stimulation has inhibitory activity on glucose-dependent insulin secretion through the activation of the P2X7 receptor, whereas it has enhancing effect through the activation of the P2Y11 receptor in HIT-T15 cells.

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