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Interestingly, in rodent models and also in humans, the development of IR in different tissues promotes a compensatory effect in the pancreas that initially leads to hyperinsulinemia and ultimately triggers -cell failure [35, 36]

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Consistently, elevated glucose levels, impaired glucose tolerance, reduced insulin levels, decreased plasma levels of GLP-1, and downregulated mRNA expression of ileal Gcg were observed in MMI mice compared to untreated control mice (CT mice) (Supplementary Fig