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Concurrently, high glucose suppressed the tumor suppressor TIF1, further amplifying Smad-mediated transcription and elevating the expression of pro-oncogenic genes, including the epithelialmesenchymal transition markers N-cadherin and vimentin, thereby collectively fostering CRC progression

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A suggested mechanism involves prolonged GIPR agonism causing receptor degradation, reducing sustained GIP signalling and, when combined with GLP-1R agonism, causing increased weight loss ( The GLP-1R has itself several LoF variants including R380C, shown by two independent groups to have normal surface expression but reduced affinity for Exenatide (Wootten et al., 2016

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