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

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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

Keywords

  • ATP-sensitive potassium channel
  • Calcium channel
  • Exocytosis
  • Ghrelin
  • Glucose
  • Total internal reflection fluorescence microscopy

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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  • 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