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Native amylin is notoriously difficult to work with because it aggregates to form amyloid fibrils (a property exploited by the pancreatic amyloid deposits seen in T2D progression)
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Based on observational data, a 2011 report highlighted an increased risk of pancreatitis and pancreatic cancer in patients using incretin therapy (Elashoff et al., 2011), prompting a warning from the Food and Drug Administration (FDA) regarding the pancreatic safety of GLP-1 RAs (Franks et al., 2012) further heightened concerns about the potential adverse effects of GLP-1RAs on the pancreas, resulting in elevated pancreatic enzymes and AP
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The direct relationship between tryptophan levels and depressive symptoms and fatigue has been demonstrated by Trp depletion experiments, as reviewed elsewhere [76], and is also of interest in the context of long-term COVID, as recent studies have shown a significant decrease in plasma Trp levels in PASC patients [48], and alterations in kynurenine pathway metabolites have been associated with cognitive impairment in long COVID patients [27], as well as with anxiety and depressive symptoms in COVID-19 survivors 6 months post-infection [66]
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