Reply to Rodgers: The hepatic glucose-mobilizing effect of glucagon is not mediated by cyclic AMP most of the time

摘要

A central dogma in glucagon biology is the acute effects of glucagon on hepatic glucose production. However, this needs to be put into a physiological context hereof to insulin levels. Dr. Rodgers argues that glucagon effect on glucose production may not be dependent on cyclic AMP "most of the time" (1). The main argument made by Dr. Rodgers appears to be a lack of "sufficient" glucagon levels in the portal vein to induce glucose production from the liver via cAMP. Some counterarguments must be considered. First, accurate measurement of glucagon is still after more than 50 years, limited (2). Not only will most glucagon assays used have an inherent specificity challenge but also the lack of and use of assay standards calibrated toward an international reference value (3) preclude comparisons of absolute glucagon concentrations. Taken together, we need new studies using more accurate glucagon immunoassays of portal levels of glucagon in humans. Finally, as previously shown, glucagon levels are two to threefold higher in samples that have not been subjected to a freeze-thaw cycle (4). Collectively, drawing conclusions merely on portal levels of glucagon may not be valid.