Abstract
Ghrelin is synthesized in X/A-like cells of the gastric mucosa, which plays an important role in the regulation of energy homeostasis. Although ghrelin secretion is known to be induced by neurotransmitters or hormones or by nutrient sensing in the ghrelin-secreting cells themselves, the mechanismof ghrelin secretion is not clearly understood. In the present study, we found that changing the extracellular glucose concentration from elevated (25 mM) to optimal (10 mM) caused an increase in the intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<inf>i</inf>) in ghrelin-secreting mouse ghrelinoma 3-1 (MGN3-1) cells (n=32, P<0.01), whereas changing the glucose concentration from elevated to lowered (5 or 1 mM) had little effect on [Ca<sup>2+</sup>]<inf>i</inf> increase. Overexpression of a closed form of an ATP-sensitive K<sup>+</sup> (K<inf>ATP</inf>) channel mutant suppressed the 10 mM glucose-induced [Ca<sup>2+</sup>]<inf>i</inf> increase (n=8, P<0.01) and exocytotic events (n=6, P<0.01).We also found that a low concentration of a K<inf>ATP</inf> channel opener, diazoxide, with 25 mM glucose induced [Ca<sup>2+</sup>]<inf>i</inf> increase (n=23, P<0.01) and ghrelin secretion (n≥3, P<0.05). In contrast, the application of a low concentration of a K<inf>ATP</inf> channel blocker, tolbutamide, significantly induced [Ca<sup>2+</sup>]<inf>i</inf> increase (nZ15, P<0.01) and ghrelin secretion (n≥3, P<0.05) under 5 mMglucose. Furthermore, the application of voltage-dependent Ca<sup>2+</sup> channel inhibitors suppressed the 10 mM glucose-induced [Ca<sup>2+</sup>]<inf>i</inf> increase (n≥26, P<0.01) and ghrelin secretion (n≥5, P<0.05). These findings suggest that K<inf>ATP</inf> and voltage-dependent Ca<sup>2+</sup> channels are involved in glucose-dependent ghrelin secretion in MGN3-1 cells.
| Original language | English |
|---|---|
| Pages (from-to) | 25-34 |
| Number of pages | 10 |
| Journal | Journal of Endocrinology |
| Volume | 226 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2015 |
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Keywords
- ATP-sensitive potassium channel
- Calcium channel
- Exocytosis
- Ghrelin
- Glucose
- Total internal reflection fluorescence microscopy
ASJC Scopus subject areas
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel. / Oya, Manami; Kitaguchi, Tetsuya; Harada, Kazuki; Numano, Rika; Sato, Takahiro; Kojima, Masayasu; Tsuboi, Takashi.
In: Journal of Endocrinology, Vol. 226, No. 1, 2015, p. 25-34.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel
AU - Oya, Manami
AU - Kitaguchi, Tetsuya
AU - Harada, Kazuki
AU - Numano, Rika
AU - Sato, Takahiro
AU - Kojima, Masayasu
AU - Tsuboi, Takashi
PY - 2015
Y1 - 2015
N2 - Ghrelin is synthesized in X/A-like cells of the gastric mucosa, which plays an important role in the regulation of energy homeostasis. Although ghrelin secretion is known to be induced by neurotransmitters or hormones or by nutrient sensing in the ghrelin-secreting cells themselves, the mechanismof ghrelin secretion is not clearly understood. In the present study, we found that changing the extracellular glucose concentration from elevated (25 mM) to optimal (10 mM) caused an increase in the intracellular Ca2+ concentration ([Ca2+]i) in ghrelin-secreting mouse ghrelinoma 3-1 (MGN3-1) cells (n=32, P<0.01), whereas changing the glucose concentration from elevated to lowered (5 or 1 mM) had little effect on [Ca2+]i increase. Overexpression of a closed form of an ATP-sensitive K+ (KATP) channel mutant suppressed the 10 mM glucose-induced [Ca2+]i increase (n=8, P<0.01) and exocytotic events (n=6, P<0.01).We also found that a low concentration of a KATP channel opener, diazoxide, with 25 mM glucose induced [Ca2+]i increase (n=23, P<0.01) and ghrelin secretion (n≥3, P<0.05). In contrast, the application of a low concentration of a KATP channel blocker, tolbutamide, significantly induced [Ca2+]i increase (nZ15, P<0.01) and ghrelin secretion (n≥3, P<0.05) under 5 mMglucose. Furthermore, the application of voltage-dependent Ca2+ channel inhibitors suppressed the 10 mM glucose-induced [Ca2+]i increase (n≥26, P<0.01) and ghrelin secretion (n≥5, P<0.05). These findings suggest that KATP and voltage-dependent Ca2+ channels are involved in glucose-dependent ghrelin secretion in MGN3-1 cells.
AB - Ghrelin is synthesized in X/A-like cells of the gastric mucosa, which plays an important role in the regulation of energy homeostasis. Although ghrelin secretion is known to be induced by neurotransmitters or hormones or by nutrient sensing in the ghrelin-secreting cells themselves, the mechanismof ghrelin secretion is not clearly understood. In the present study, we found that changing the extracellular glucose concentration from elevated (25 mM) to optimal (10 mM) caused an increase in the intracellular Ca2+ concentration ([Ca2+]i) in ghrelin-secreting mouse ghrelinoma 3-1 (MGN3-1) cells (n=32, P<0.01), whereas changing the glucose concentration from elevated to lowered (5 or 1 mM) had little effect on [Ca2+]i increase. Overexpression of a closed form of an ATP-sensitive K+ (KATP) channel mutant suppressed the 10 mM glucose-induced [Ca2+]i increase (n=8, P<0.01) and exocytotic events (n=6, P<0.01).We also found that a low concentration of a KATP channel opener, diazoxide, with 25 mM glucose induced [Ca2+]i increase (n=23, P<0.01) and ghrelin secretion (n≥3, P<0.05). In contrast, the application of a low concentration of a KATP channel blocker, tolbutamide, significantly induced [Ca2+]i increase (nZ15, P<0.01) and ghrelin secretion (n≥3, P<0.05) under 5 mMglucose. Furthermore, the application of voltage-dependent Ca2+ channel inhibitors suppressed the 10 mM glucose-induced [Ca2+]i increase (n≥26, P<0.01) and ghrelin secretion (n≥5, P<0.05). These findings suggest that KATP and voltage-dependent Ca2+ channels are involved in glucose-dependent ghrelin secretion in MGN3-1 cells.
KW - ATP-sensitive potassium channel
KW - Calcium channel
KW - Exocytosis
KW - Ghrelin
KW - Glucose
KW - Total internal reflection fluorescence microscopy
UR - http://www.scopus.com/inward/record.url?scp=84935145080&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84935145080&partnerID=8YFLogxK
U2 - 10.1530/JOE-15-0090
DO - 10.1530/JOE-15-0090
M3 - Article
C2 - 26099355
AN - SCOPUS:84935145080
VL - 226
SP - 25
EP - 34
JO - Journal of Endocrinology
JF - Journal of Endocrinology
SN - 0022-0795
IS - 1
ER -