Glucose-mediated control of ghrelin release from primary cultures of gastric mucosal cells

Ichiro Sakata, Won Mee Park, Angela K. Walker, Paul K. Piper, Jen Chieh Chuang, Sherri Osborne-Lawrence, Jeffrey M. Zigman

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

The peptide hormone ghrelin is released from a distinct group of gastrointestinal cells in response to caloric restriction, whereas its levels fall after eating. The mechanisms by which ghrelin secretion is regulated remain largely unknown. Here, we have used primary cultures of mouse gastric mucosal cells to investigate ghrelin secretion, with an emphasis on the role of glucose. Ghrelin secretion from these cells upon exposure to different D-glucose concentrations, the glucose antimetabolite 2-deoxy-D-glucose, and other potential secretagogues was assessed. The expression profile of proteins involved in glucose transport, metabolism, and utilization within highly enriched pools of mouse ghrelin cells and within cultured ghrelinoma cells was also determined. Ghrelin release negatively correlated with D-glucose concentration. Insulin blocked ghrelin release, but only in a low D-glucose environment. 2-Deoxy-D-glucose prevented the inhibitory effect of high D-glucose exposure on ghrelin release. mRNAs encoding several facilitative glucose transporters, hexokinases, the ATPsensitive potassium channel subunit Kir6.2, and sulfonylurea type 1 receptor were expressed highly within ghrelin cells, although neither tolbutamide nor diazoxide exerted direct effects on ghrelin secretion. These findings suggest that direct exposure of ghrelin cells to low ambient D-glucose stimulates ghrelin release, whereas high D-glucose and glucose metabolism within ghrelin cells block ghrelin release. Also, low D-glucose sensitizes ghrelin cells to insulin. Various glucose transporters, channels, and enzymes that mediate glucose responsiveness in other cell types may contribute to the ghrelin cell machinery involved in regulating ghrelin secretion under these different glucose environments, although their exact roles in ghrelin release remain uncertain.

Original languageEnglish (US)
Pages (from-to)E1300-E1310
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume302
Issue number10
DOIs
StatePublished - May 15 2012

Keywords

  • Secretion

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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