T2DM and prediabetes are characterized by abnormal post-prandial suppression of glucagon, which contributes to postprandial hyperglycemia by increasing endogenous glucose production (EGP). In rodents, altered glucagon signaling changes α-cell function and mass - an effect mediated by changes in circulating AA concentrations. Are the elevated concentrations of branched-chain AA and other AA metabolites in T2DM a cause or an effect of global α-cell dysfunction? To measure glucagon secretion, as well as glucagon action, we have developed a population model of glucagon kinetics allowing us to deconvolve secretion from glucagon concentrations in a manner similar to Van Cauter's model for insulin secretion from C-peptide. This enables better characterization of α-cell function in humans. In addition to our novel methodology, we can characterize α-cell responsiveness to a graded glucose infusion, by quantifying (G50) - the change in glucose concentration necessary to suppress glucagon secretion by 50%. These experiments will determine if the glucagon secretion in response to AA differs in obese individuals with T2DM from that observed in obese individuals without T2DM.
This study is being done to better understand how amino acids alter the release of glucagon and insulin compared to glucose alone in health and disease.