The Effects of Glucagon on Hepatic Metabolism in People With Type 2 Diabetes After Caloric Restriction
Adrian Vella
Summary
Caloric restriction (and RYGB) improves insulin action and lowers fasting glucose, glucagon and EGP, without changes in postprandial EGP and glucagon concentrations. Caloric restriction also improves hepatic steatosis and lowers fasting AA. These changes may represent restoration of glucagon's hepatic actions. This experiment will determine whether caloric restriction improves glucagon's actions on hepatic amino acid, carbohydrate and lipid metabolism in T2DM in comparison to a baseline experiment performed separately in people with T2DM.
Description
T2DM and prediabetes are characterized by abnormal post-prandial suppression of glucagon, which contributes to postprandial hyperglycemia by increasing EGP. Although these effects are magnified by decreased and delayed insulin secretion, they are also apparent when insulin secretion is intact5. 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? Could altered glucagon signal…
Eligibility
- Age range
- 25–65 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * We will recruit up to 20 weight-stable, subjects with type 2 diabetes * BMI ≥ 28 Kg/M2 * Diabetes is managed by diet alone or a combination of oral agents 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.
Interventions
- BehavioralCaloric Restriction
Subjects will be instructed to consume a diet of 900 kcal daily using meals derived from "Nutritional Guidelines after Bariatric Surgery". Compliance will be monitored by weekly meetings with the dietician using an electronic record of food intake
- DrugHyperglycemic clamp
Hyperglycemic clamp to measure the effect of glucagon on hepatic metabolism
Location
- Mayo Clinic in RochesterRochester, Minnesota