The Effects of Glucagon on Hepatic Metabolism

22-000113

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).

2022-10-20

2025-09-30

2025-12-31

Recruiting

Early phase I

60

Inclusion Criteria: * Willing to participate * Able to give consent Exclusion Criteria: * History of prior upper abdominal surgery e.g. gastric banding, pyloroplasty, vagotomy. * Active systemic illness or malignancy. * Symptomatic macrovascular or microvascular disease. * Contraindications to MRI (e.g. metal implants, claustrophobia). * Hematocrit \< 35% * TSH \< 0.4 or \> 5.5. * Consumption of \> 2 alcohol drinks per day or \> 14 per week or a positive AUDIT questionnaire

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'All subjects will undergo one study designed to measure the hepatic response to glucagon. There will be 3 groups non-diabetic and non-obese, obese, people with type 2 diabetes', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 60, 'type': 'ESTIMATED'}}

2024-05-29