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 language | English |
|---|---|
| Pages (from-to) | 302-308 |
| Number of pages | 7 |
| Journal | Pancreas |
| Volume | 37 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2008 Oct 1 |
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All Science Journal Classification (ASJC) codes
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Hepatology
- Endocrinology
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Dual effect of ATP on glucose-induced insulin secretion in HIT-T15 cells. / Lee, Dong Hyeon; Park, Kyu Sang; Kim, Dae Ran; Lee, Joong Woo; Kong, In Deok.
In: Pancreas, Vol. 37, No. 3, 01.10.2008, p. 302-308.Research output: Contribution to journal › Article
TY - JOUR
T1 - Dual effect of ATP on glucose-induced insulin secretion in HIT-T15 cells
AU - Lee, Dong Hyeon
AU - Park, Kyu Sang
AU - Kim, Dae Ran
AU - Lee, Joong Woo
AU - Kong, In Deok
PY - 2008/10/1
Y1 - 2008/10/1
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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U2 - 10.1097/MPA.0b013e318168daaa
DO - 10.1097/MPA.0b013e318168daaa
M3 - Article
C2 - 18815553
AN - SCOPUS:58149340154
VL - 37
SP - 302
EP - 308
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 3
ER -