Metformin directly inhibits ghrelin secretion through AMP‐activated protein kinase in rat primary gastric cells

Abstract

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.

Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid

“…The classical ghrelin effects work through ghrelin receptors since they are abolished in ghrelin receptor knockout mice [30]. Metformin administration causes weight loss and suppresses hepatic gluconeogenesis by activating hepatic AMPK activation, which is consistent with recent research demonstrating that inhibiting ghrelin secretion is one of the key features of metformin action [31]. These results suggest that AMPK activation is tissue-specific and ghrelin activates AMPK in the brain.…”

“…The β-amyloid (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and β-amyloid were dissolved in sterile saline and stored at −20°C before use. The infusion of β-amyloid (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) into the LV causes the accumulation of β-amyloid whereas the infusion of β-amyloid , the reverse sequence of β-amyloid (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), does not accumulate in the brain, as confirmed by immunohistochemistry using β-amyloid antibody [4,21].…”

“…The infusion of β-amyloid (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) into the LV causes the accumulation of β-amyloid whereas the infusion of β-amyloid , the reverse sequence of β-amyloid (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), does not accumulate in the brain, as confirmed by immunohistochemistry using β-amyloid antibody [4,21]. Each β-amyloid solution was infused via an osmotic pump (Alzet Osmotic Pump Company, Cupertino, CA) at the rate of 16.8 nmol/day for 3 days.…”

“…Each β-amyloid solution was infused via an osmotic pump (Alzet Osmotic Pump Company, Cupertino, CA) at the rate of 16.8 nmol/day for 3 days. The cannula was secured with dental cement and connected to 22-gauge tubing filled with one of the following: β-amyloid (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), designated AD; β-amyloid (35-25) designated Non-AD (negative control).…”

MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome

“…Treatment with metformin for 6 months or less had a limited effect on weight loss (74), whereas 12 months treatment induced a median weight loss of 3 kg (64). Decreased adipokine and ghrelin levels during metformin treatment could induce weight loss (74,76), but this hypothesis needs further testing.…”