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Metformin directly inhibits ghrelin secretion through AMP ‐activated protein kinase in rat primary gastric cells
Author(s) -
Gag J.,
Sheppard E.,
Anini Y.
Publication year - 2013
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12021
Subject(s) - metformin , ampk , ghrelin , medicine , endocrinology , orexigenic , protein kinase a , amp activated protein kinase , secretion , activator (genetics) , chemistry , biology , kinase , hormone , diabetes mellitus , receptor , biochemistry , neuropeptide , neuropeptide y receptor
The antidiabetic drug Metformin causes weight loss in both diabetic and non‐diabetic individuals. Metformin treatment is also associated with lower circulating levels of the orexigenic hormone ghrelin. To test whether Metformin directly affects ghrelin cells, rat primary stomach cells were treated with Metformin and the levels of ghrelin secretion, proghrelin gene expression and activation of adenosine monophosphate‐activated protein kinase ( AMPK ) were examined. Metformin significantly reduced ghrelin secretion and proghrelin mRNA production and both these effects were blocked by co‐incubation with the AMPK inhibitor compound C. Furthermore, the AMPK activator 5‐amino‐1‐β‐D‐ribofuranosyl‐imidazole‐4‐carboxamide ( AICAR ) significantly inhibited ghrelin secretion. Additionally, ghrelin cells were shown to express AMPK . Finally, Metformin treatment caused a significant increase in the level of phosphorylated (active) AMPK . Our results show that Metformin directly inhibits stomach ghrelin production and secretion through AMPK . This reduction in ghrelin secretion may be one of the key components in Metformin's mechanism of weight loss.