TY - JOUR
T1 - Lowering oxidative stress in ghrelin cells stimulates ghrelin secretion
AU - Mani, Bharath K.
AU - Osborne-Lawrence, Sherri
AU - Metzger, Nathan
AU - Zigman, Jeffrey M.
N1 - Publisher Copyright:
Copyright © 2020 the American Physiological Society
PY - 2020/8
Y1 - 2020/8
N2 - Ghrelin is a predominantly stomach-derived peptide hormone with many actions including regulation of food intake, body weight, and blood glucose. Plasma ghrelin levels are robustly regulated by feeding status, with its levels increasing upon caloric restriction and decreasing after food intake. At least some of this regulation might be due to direct responsiveness of ghrelin cells to changes in circulating nutrients, including glucose. Indeed, oral and parental glucose administration to humans and mice lower plasma ghrelin. Also, dissociated mouse gastric mucosal cell preparations, which contain ghrelin cells, decrease ghrelin secretion when cultured in high ambient glucose. Here, we used primary cultures of mouse gastric mucosal cells in combination with an array of pharmacological tools to examine the potential role of changed intracellular oxidative stress in glucose-restricted ghrelin secretion. The antioxidants resveratrol, SRT1720, and curcumin all markedly increased ghrelin secretion. Furthermore, three different selective activators of Nuclear factor erythroid-derived-2-like 2 (Nrf2), a master regulator of the antioxidative cellular response to oxidative stress, increased ghrelin secretion. These antioxidant compounds blocked the inhibitory effects of glucose on ghrelin secretion. Therefore, we conclude that lowering oxidative stress within ghrelin cells stimulates ghrelin secretion and blocks the direct effects of glucose on ghrelin cells to inhibit ghrelin secretion.
AB - Ghrelin is a predominantly stomach-derived peptide hormone with many actions including regulation of food intake, body weight, and blood glucose. Plasma ghrelin levels are robustly regulated by feeding status, with its levels increasing upon caloric restriction and decreasing after food intake. At least some of this regulation might be due to direct responsiveness of ghrelin cells to changes in circulating nutrients, including glucose. Indeed, oral and parental glucose administration to humans and mice lower plasma ghrelin. Also, dissociated mouse gastric mucosal cell preparations, which contain ghrelin cells, decrease ghrelin secretion when cultured in high ambient glucose. Here, we used primary cultures of mouse gastric mucosal cells in combination with an array of pharmacological tools to examine the potential role of changed intracellular oxidative stress in glucose-restricted ghrelin secretion. The antioxidants resveratrol, SRT1720, and curcumin all markedly increased ghrelin secretion. Furthermore, three different selective activators of Nuclear factor erythroid-derived-2-like 2 (Nrf2), a master regulator of the antioxidative cellular response to oxidative stress, increased ghrelin secretion. These antioxidant compounds blocked the inhibitory effects of glucose on ghrelin secretion. Therefore, we conclude that lowering oxidative stress within ghrelin cells stimulates ghrelin secretion and blocks the direct effects of glucose on ghrelin cells to inhibit ghrelin secretion.
KW - Antioxidants
KW - Ghrelin
KW - Glucose
KW - Oxidative stress
KW - Primary culture
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U2 - 10.1152/AJPENDO.00119.2020
DO - 10.1152/AJPENDO.00119.2020
M3 - Article
C2 - 32543942
AN - SCOPUS:85088488528
SN - 0193-1849
VL - 319
SP - E330-E337
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 2
ER -