DPP4 Inhibition & Beta Cell Function
Condition: Healthy
Intervention: Active Comparator: Sitagliptin; Placebo Comparator - No Sitagliptin
Intervention description: Subjects will receive sitagliptin prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).; Subjects will receive Placebo (instead of sitagliptin) prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).
Intervention MeSH terms: Sitagliptin Phosphate
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Enrollment: 40.0
Sex: All
Minimum age: 35 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: insulin secretion; GLP-1; alpha cell; paracrine effect; Glucagon-Like Peptide 1

Summary:

      This study is being done to determine the role of a hormone, glucagon-like peptide 1 (GLP-1),
      on insulin secretion and to study how GLP-1 works in in diabetic individuals as compared to
      non-diabetic individuals, under fasting conditions.

      GLP-1 is a naturally occurring hormone made in the intestines. It is released into the
      circulating blood after eating and helps to control the blood glucose levels by increasing
      insulin secretion by cells in the pancreas. However, the exact method by which GLP-1 causes
      insulin secretion and how GLP-1 activity is changed in diabetic persons remain unclear. This
      research is being done to address these questions and better understand the function of
      GLP-1.

      In this research, the investigators will use a synthetic form of Exendin-9 to determine the
      effects of GLP-1 on insulin secretion in diabetic and non-diabetic persons. Exendin-9 acts as
      a blocker of GLP-1 action, allowing us to study the specific effects of the GLP-1 hormone.
      Exendin-9 is an investigational compound, which means it is still being tested in research
      studies and is not approved by the U.S. Food and Drug Administration (FDA).

      In this study, the investigators will also use the drug Sitagliptin, which is an FDA-approved
      drug for the treatment of type 2 diabetes mellitus. In this study, use of Sitagliptin is
      considered investigational since it is not being used for treatment of diabetes but is
      instead being used to understand how GLP-1 works and to better understand how medications
      like Sitagliptin work in patients with type 2 diabetes mellitus.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diabetic cohort: adults age 35-70 years with Type 2 diabetes managed by an oral
             medication or diet and exercise

          -  Non-diabetic cohort: healthy adults age 35-70 years

          -  Male or female

          -  Ability to speak and understand English

          -  Diabetic cohort: HbA1c ≤ 8.0%

          -  Non-diabetic cohort: HbA1c ≤ 6.2%

        Exclusion Criteria:

          -  Rheumatoid arthritis

          -  Inflammatory bowel disease

          -  Unstable angina or uncompensated heart failure

          -  Pulmonary disorders, including COPD and asthma

          -  Malabsorptive GI disease, such as celiac disease, or gastric bypass

          -  Significant hepatic disease

          -  Renal insufficiency (eGFR < 60 mL/kg/min)

          -  Anemia (hematocrit < 34%) as measured at screening visit

          -  Uncontrolled hypertension

          -  Pregnant females

          -  Consumption of daily medications that alter glucose metabolism of GI function
             (glucocorticoids, psychotropics, narcotics, metoclopramide)

          -  Consumption or injection of insulin

          -  Apparent sensitivity to any of the study peptides as determined by the skin test