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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
30
Intravenous graded glucose infusion using 50% dextrose will commence at 1mg/kg/min and increase to 2 (0900), 4 (1000) and 8mg/kg/min (1100) every 60 minutes
Intravenous infusion 0.003ml/kg/min infused from 0 to 240 minutes
Mayo Clinic Rochester
Rochester, Minnesota, United States
Change in Glucagon Suppression (G50) caused by amino acids vs. saline
concentration of glucose necessary to suppress glucagon by 50%
Time frame: 240 minutes of study
Glucagon suppression (G50) is greater in people with T2DM
concentration of glucose necessary to suppress glucagon by 50%
Time frame: 240 minutes of study
glucagon suppression (G50) is greater in obese compared to lean people without T2DM
concentration of glucose necessary to suppress glucagon by 50%
Time frame: 240 minutes of study
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