INS and Hyperglycemia: FGF21 was, however, increased by hyperglycemia under pancreatic clamp conditions (<i>P</i> < 0.05), while GLP-1 infusion under pancreatic clamp conditions did not change circulating FGF21 levels.<h4>Conclusion</h4>Increases in plasma FGF21 are <i>likely</i> driven directly by changes in plasma glucose independent of changes in insulin or GLP-1 secretion.