The goal of this study is to understand the role of glucagon signal on glucose metabolism in individuals with and without bariatric surgery. The study is involved with measuring glucose metabolism with glucagon infusion and glucagon receptor blockade. We use an investigational drug called REMD 477. "Investigational" means that the has not yet been approved by the U.S. Food \& Drug Administration (FDA). REMD-477 is a monoclonal antibody (an antibody made by cloning a unique white blood cell) that blocks the effect of glucagon.
Participants will be screened, and if eligible will be enrolled for metabolic studies for two separate aims. In aim 1, they undergo glucose clamp study with and without glucagon infusion. In aim 2, they undergo 2-day meal studies with and without a single dose administration of investigational drug, REMD 477 using a small needle subcutaneously. During these studies glycemic profile will be evaluated using CGM (Continuous glucose monitoring). Participants will also have a blood draw for liver enzymes8 weeks after the administration of REMD 477. Participants will spend up to 3- 6 months participating in any pair study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
150
Placebo versus glucagon receptor antagonist using a human monoclonal antibody with a high level of antagonistic effect against human glucagon receptor.
The effect of increased glucagon concentrations in plasma on glucose metabolism during glucose clamp will be studied.
Texas Diabetes Institute - University Health System
San Antonio, Texas, United States
RECRUITINGUniversity of Texas San Antonio
San Antonio, Texas, United States
RECRUITINGGlycemc response to meal ingestion
Changes in glucose response to meal ingestion occurred by administration of glucagon receptor antagonist (GRA).
Time frame: 0 to 240 minutes
Endogenous glucose production (EGP) during clamp studies
Changes in EGP (measured by tracer technique) with and without glucagon infusion
Time frame: 0 to 240 minutes
Prandial glucose kinetics
Glucose flux with and without GRA administration
Time frame: Baseline to 240 minutes
Plasma GLP-1, GIP, insulin and glucagon concentrations
Changes in these outcomes following meal ingestion with and without GRA administration
Time frame: 0 to 240 minutes
Glucose clearance and insulin and glucagon concentrations during clamp studies
Outcomes with and without glucagon infusion
Time frame: 0 to 240 minutes
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