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Loss of SIRT4 decreases GLT-1-dependent glutamate uptake and increases sensitivity to kainic acid

150,152,153 Activation of the GLP-1R can enhance insulin secretion, reduce glucagon secretion, delay gastric emptying, 154 and suppress appetite

Mechanism involves NO system modulation (homeostatic regulationupregulating when deficient, moderating when excessive), VEGF/VEGFR2 upregulation for angiogenesis, FAK-paxillin pathway activation for cell migration (40% increase per Chang et al.), and EGR-1 transcription factor upregulation for growth factor sensitivity

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Furthermore, GPR81 modulates the expression of lactate-handling genes such as MCT1/4, indicating its feedback control over both lactate signaling and transport [204]