Regulation of Insulin Secretion by the GLP-1 Receptor

• Status: Recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

AIM2: The purpose of Aim-2 of this study is to determine the role of basal GLP-1 action on the beta-cell response to insulin resistance. Healthy subjects will have fasting GLP-1 action determined with GLP-1r blockade before and after induction of experimental insulin resistance. The investigators hypothesize that fasting GLP-1 action will increase to compensate for experimental insulin resistance.

AIM3: The purpose of Aim-3 of this study is to determine the role of basal GLP-1 action on fasting glucose regulation in lean, obese, pre-diabetic and type 2 diabetic (T2DM) subjects. A cross sectional study of age-matched subjects across the spectrum of glucose tolerance will be used to test the hypothesis that fasting GLP-1 action increases as beta-cell function declines.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: David D'Alessio, M.D.; VA Office of Research and Development
• Collaborator: Durham VA Medical Center
• Treatments: Dexamethasone; Glucagon; Glucagon-Like Peptide 1

Criteria

Inclusion Criteria:

AIM2: SELECTION OF HEALTHY SUBJECTS

• Healthy adults age 20-45 years

• Body Mass Index (BMI) less than or equal to 35.0 kg/m2

• HbA1c less than or equal to 5.7% as measured at screening visit

• Ability to speak and understand English

AIM3: NON-DIABETIC SUBJECTS

• Adults age 18-65 years

• Body Mass Index (BMI) 25-40.0 kg/m2

• HbA1c less than or equal to 6.5% as measured at screening visit

• No Diabetes or use of diabetes medications such as insulin or metformin

• Ability to speak and understand English

AIM3: DIABETIC Type II SUBJECTS

• Adults age 18-65 years

• Body Mass Index (BMI) 25-40.0 kg/m2

• HbA1c less than or equal to 7.5% plus a diagnosis of Type II diabetes managed by either Metformin, Sulfonylurea, or diet and exercise

• Ability to speak and understand English

Exclusion Criteria:

AIM2:

• Uncontrolled high blood pressure

• Diabetes or use of diabetes medications such as insulin or metformin

• Evidence of active heart disease, unstable angina or heart failure

• Lung disease or COPD

• Malabsorptive GI disease, such as celiac disease, or gastric bypass

• Significant hepatic disease

• Kidney disease or renal insufficiency (eGFR < 60 mL/kg/min)

• Untreated anemia (hematocrit < 34%) as measured at screening visit

• Pregnant females

• Active substance abuse

• Chronic use of oral steroid medications such as prednisone and hydrocortisone

• Apparent sensitivity to any study peptides as determined by the skin test

• Diagnosis or h/o PTSD

• Active mental health disorders such as depression, or as a result of Traumatic Brain Injury (TBI)

AIM3: ALL SUBJECTS

• Uncontrolled high blood pressure

• Evidence of active heart disease, unstable angina or heart failure

• Lung disease or COPD

• Malabsorptive GI disease, such as celiac disease, or gastric bypass

• Significant hepatic disease

• Kidney disease or renal insufficiency (eGFR < 60 mL/kg/min)

• Untreated anemia (hematocrit < 34%) as measured at screening visit

• Pregnant females

• Active substance abuse

• Chronic use of oral steroid medications such as prednisone and hydrocortisone

• Apparent sensitivity to any study peptides as determined by the skin test

• Diagnosis or h/o PTSD

• Active mental health disorders such as depression, or as a result of Traumatic Brain Injury (TBI)