Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel

Manami Oya, Tetsuya Kitaguchi, Kazuki Harada, Rika Numano, Takahiro Sato, Masayasu Kojima, Takashi Tsuboi

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 languageEnglish
Pages (from-to)25-34
Number of pages10
JournalJournal of Endocrinology
Volume226
Issue number1
DOIs
Publication statusPublished - 2015

Fingerprint

KATP Channels
Ghrelin
Glucose
Diazoxide
Tolbutamide
Gastric Mucosa
Neurotransmitter Agents
Homeostasis
Adenosine Triphosphate
Hormones
Food
N-(4-pyridylcarbonylamino)-1,2,3,6-tetrahydropyridine

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

Oya, M., Kitaguchi, T., Harada, K., Numano, R., Sato, T., Kojima, M., & Tsuboi, T. (2015). Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel. Journal of Endocrinology, 226(1), 25-34. https://doi.org/10.1530/JOE-15-0090

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 journalArticle

Oya, M, Kitaguchi, T, Harada, K, Numano, R, Sato, T, Kojima, M & Tsuboi, T 2015, 'Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel', Journal of Endocrinology, vol. 226, no. 1, pp. 25-34. https://doi.org/10.1530/JOE-15-0090
Oya, Manami ; Kitaguchi, Tetsuya ; Harada, Kazuki ; Numano, Rika ; Sato, Takahiro ; Kojima, Masayasu ; Tsuboi, Takashi. / Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel. In: Journal of Endocrinology. 2015 ; Vol. 226, No. 1. pp. 25-34.
@article{5ec84002a6ac47189d0636b02761ce18,
title = "Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel",
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 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.",
keywords = "ATP-sensitive potassium channel, Calcium channel, Exocytosis, Ghrelin, Glucose, Total internal reflection fluorescence microscopy",
author = "Manami Oya and Tetsuya Kitaguchi and Kazuki Harada and Rika Numano and Takahiro Sato and Masayasu Kojima and Takashi Tsuboi",
year = "2015",
doi = "10.1530/JOE-15-0090",
language = "English",
volume = "226",
pages = "25--34",
journal = "Journal of Endocrinology",
issn = "0022-0795",
publisher = "Society for Endocrinology",
number = "1",

}

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

VL - 226

SP - 25

EP - 34

JO - Journal of Endocrinology

JF - Journal of Endocrinology

SN - 0022-0795

IS - 1

ER -