Impact of Dopamine Infusion on Insulin Secretion in Healthy Subjects

Rationale Role of dopamine infusion on pancreatic beta cell function in health and disease
remain undetermined in humans. Increasingly, hyperglycemia in the critical care arena bodes
poorly on health outcomes.

This study for the first time investigates the role of dopamine infusion in health and has
the potential to guide larger studies on impact of dopamine use in critical illness.

Study Design This project will be a prospective, single-center trial to determine the effect
of dopamine in healthy subjects using the hyperglycemic clamp.

Study Procedures:

After signing informed consent subjects will undergo screening at the clinical research
center after an overnight fast. At this visit, a complete history and physical exam
including vital signs, height, weight, BMI, waist circumference will be obtained. Cardiac
conditions will be screened using an EKG. Baseline labs will be drawn at this visit,
including CBC, chemistry, liver function tests, hemoglobin AIC, thyroid function tests,
lipids and cortisol. Females will have a urine beta HCG.

Subjects that meet study criteria will return within 30 days of screening to the clinical
research after an overnight fast. One large bore (20 gauge) venous cannula will be inserted
in the antecubital fossa for infusion of dopamine and dextrose 20% intravenous solution.
Another cannula will be inserted in the contralateral arm for frequent blood sampling.

Insulin sensitivity will be determined using the gold standard hyperglycemic clamp as
previously described (DeFronzo, 1979).13 Each subject will act as their own control and
receive placebo infusion followed by dopamine infusions.

Subjects will have their blood pressure, heart rate, and glucose monitored every 10 minutes.
Each subject will receive a priming dose of dextrose 20% to increase their glucose
concentration by 125 mg/dl in the first 15 minutes. Then they will receive variable rates of
dextrose 20% infusion to maintain glucose level at 180-220 mg/dl. C-peptide, insulin,
glucagon and catecholamine levels will be drawn at 30 min and 60 min to determine baseline
levels prior to dopamine infusion. Then, dopamine (200mg/250ml) will be titrated up to 5
mcg/kg/min with care not to increase blood pressure greater than 160 systolic. C-peptide,
insulin level, glucagon, plasma catecholamines will be measured at 90 min and 120 min,
150min, 180min, 210min, 240min. At 120min, 180 min and 240 min glucagon and cortisol levels
will also be measured. The total amount of blood withdrawn for entire study will be less
than 100 ml. After all blood samples are drawn, dextrose and dopamine infusion will be
down-titrated and stopped. The subject will be given lunch and glucose level will be
checked. Venous cannulas will then be removed and subject will be sent home.

Inclusion Criteria:

1. Healthy subjects

2. Age 18-35 years

3. Hemoglobin >12 g/dl

4. Euthyroid or on a stable dose of synthroid

5. Normal EKG, hemoglobin AIC, kidney and liver function

Exclusion Criteria:

1. Prior history of dopamine infusion

2. Past medical history of diabetes, hypertension, myocardial infarction, vaso-occlusive
disease or arrhythmias

3. Chronic steroid therapy, oral contraceptive pills, monoamine oxidase inhibitors
(MAO-I), anticonvulsants (phenytoin)

4. Pregnant women because dopamine is pregnancy category C

5. Clinical signs of polycystic ovarian syndrome

6. Past medical history of Cushing's disease or pheochromocytoma

7. Sulfa drug allergy

8. Use of any medications or illness determined by the investigators that may affect
insulin secretion or insulin sensitivity.