Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to
overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell
function, or a combination of both are important, unanswered questions. NAFLD is associated
with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon
resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will
determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with
hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying
degrees of hepatic steatosis).