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In this review, we highlight molecular mechanisms and the functional importance of FGF21 induction in response to diverse stress conditions such as changes of nutritional status, cold exposure, and exercise. In addition, we describe recent findings regarding the role of FGF21 in the pathogenesis and treatment of diabetes associated with obesity, liver diseases, pancreatitis, muscle atrophy, atherosclerosis, cardiac hypertrophy, and diabetic nephropathy. Finally, we discuss the current understanding of the actions of FGF21 as a crucial regulator mediating beneficial metabolic effects of therapeutic agents such as metformin, glucagon\/glucagon-like peptide 1 analogues, thiazolidinedione, sirtuin 1 activators, and lipoic acid.<\/jats:p>","DOI":"10.1530\/joe-15-0160","type":"journal-article","created":{"date-parts":[[2015,6,27]],"date-time":"2015-06-27T08:03:04Z","timestamp":1435392184000},"page":"R1-R16","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":59,"title":["FGF21 as a mediator of adaptive responses to stress and metabolic benefits of anti-diabetic drugs"],"prefix":"10.1530","volume":"226","author":[{"given":"Kook 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