Regulation of Endogenous Glucose Production by Central KATP Channels

In this study, the investigators will study healthy participants and participants with Type 2
diabetes through a procedure called a "pancreatic clamp" study, in which hormones such as
insulin and glucose are infused through an IV to carefully control blood sugar levels.

All participants will be screened prior to study enrollment. Eligible participants will have
2 study visits (one study with diazoxide +/- nicotinic acid and one study with placebo) that
will include overnight admissions for participants with Type 2 diabetes. Healthy participants
will not have to stay for an overnight admission.

Inclusion Criteria:

For healthy participants:

- Age: 21-65 y.o.

- BMI under 30

- Negative drug screen

- Normal A1C and fasting glucose

- No family history of diabetes among first degree relatives (eg. Mother, father)

For T2D participants:

- Age: 21-65 y.o.

- BMI under 35

- A1c 8.0-12.0%

- Negative drug screen

- Not suffering from a previously diagnosed proliferative retinopathy, significant
diabetic renal disease or symptomatic neuropathy (including cardiovascular and
gastrointestinal autonomic dysfunction).

Exclusion Criteria:

- Age: Under 21 or over 65 y.o.

- BMI: >35 for T2D and >30 for ND

- Hypertension

- Severe polydipsia and polyuria

- Urine microalbumin: >300 mg/g of creatinine (in subjects with T2D)

- Uncontrolled hyperlipidemia

- Clinically significant liver dysfunction

- Clinically significant kidney dysfunction

- Anemia

- Leukocytosis or leukopenia

- Thrombocytopenia or thrombocytosis

- Coagulopathy

- Positive urine drug screen

- Urinalysis: Clinically significant abnormalities

- Clinically significant electrolyte abnormalities

- Smoking >7 cig/day

- Alcohol: Men >14 drinks/wk or > 4drinks/day, Women > 7 drinks/wk or > 3 drinks/day

- History of chronic liver disease, active hepatitis infection, HIV/AIDS, chronic kidney
disease (stage 3 or greater), active cancer, cardiovascular disease or other heart
disease, systemic rheumatologic conditions, seizures, bleeding disorders, muscle
disease

- Surgeries that involve removal of endocrine glands except for thyroidectomy

- Pregnant women

- Subject enrolled in another study less than one month prior to the anticipated start
date of the proposed study

- Family history: family history of premature cardiac death

- Allergies to medication administered during study

- Uncontrolled psychiatric disorders

- Any condition which in the opinion of the PI makes the subject ill suited for
participation in the study