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The key mechanistic features: Gq/11 coupling activates phospholipase C- (PLC-) PLC- cleaves PIP2 generates IP3 and diacylglycerol (DAG) IP3 triggers Ca release from endoplasmic reticulum stores The calcium spike drives immediate GH vesicle exocytosis DAG activates PKC additional downstream signaling including ERK/MAPK Hexarelin's unusually strong GH response appears to involve additional mechanisms beyond standard GHSR-1a agonism

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Conversely, fasting and ghrelin stimulation have been shown to heighten Ogt expression and O-GlcNAc modification levels in AgRP neurons within the arcuate nucleus [33]

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