Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults

The investigators will study 22 healthy subjects (18-35 yrs) four times as follows:

1. Saline + Octreotide + euglycemia;

2. Octreotide + hyperglycemia;

3. Octreotide + hyperglycemia + insulin clamp and

4. Octreotide + Euglycemia + insulin clamp.

The sequence of admissions will be assigned randomly. The investigators will assess function
in conduit (pulse wave velocity-PWV, augmentation index-AI and flow-mediated dilation-FMD),
resistance (post-ischemic flow velocity-PIFV) and heart and skeletal muscle microvascular
(contrast enhanced ultrasound-CEU) vessels.

This work will:

a) identify whether vascular stiffness and indices of NO action are impaired throughout the
arterial tree with hyperglycemia.

Inclusion Criteria:

- Healthy with no chronic illness

- Age 18-35

- Normal BMI (18-25)

- Normal screening labs or no clinically significant values

Exclusion Criteria:

- First degree relative with Type 2 Diabetes

- Smoking presently or in the past 6 months

- Medications that affect the vasculature

- Overweight or other indications of insulin resistance

- Elevated LDL cholesterol > 160

- Elevated BP > 140/90

- History of congestive heart failure, ischemic heart disease, severe pulmonary disease,
liver or kidney disease, bleeding disorders

- Any vascular disease such as myocardial infarction, stroke, peripheral vascular
disease

- Presence of an intracardiac or intrapulmonary shunt (we will screen for this by
auscultation during the physical exam by PI).

- Pregnant or breastfeeding.

- Known hypersensitivity to perflutren (contained in Definity)