Inclusion Criteria:
* Type 1 diabetes mellitus for more than 5 years complicated by the following situations that persist despite intensive insulin management efforts:
* At least one episode of severe hypoglycemia in the past 3 years defined as an event with symptoms compatible with hypoglycemia in which the subject required the assistance of another person, and which was associated with either a blood glucose level \<50 mg/dL (2.8 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration
* Reduced awareness of hypoglycemia, defined by the absence of adequate autonomic symptoms at capillary glucose levels of \<54 mg/dL (3 mmol/l) as reported by the subject
Exclusion Criteria:
* Co-existing cardiac disease: myocardial infarction within the past 6 months, angiographic evidence of non-correctable coronary artery disease, ischemia on functional cardiac exam, heart failure
* Active alcohol or substance abuse, including cigarette smoking (must be abstinent for six months)
* Psychiatric disorder: schizophrenia, bipolar disorder, or major depression that is unstable on medication
* History of non-adherence to prescribed regimens
* Active infection including hepatitis C, hepatitis B, HIV
* TB by history, current infection, or under treatment for suspected TB
* History of malignancies except squamous or basal skin cancer
* Family history of MEN2 or MCT
* Stroke within the past 6 months
* BMI \>27 kg/m2
* C-peptide response to glucagon stimulation, any C-peptide \>0.3 ng/mL
* Inability to provide informed consent
* Age less than 18 or greater than 75 years
* Creatinine clearance \<80 mL/min/1.73 m2 by 24-hour urine collection
* Serum creatinine consistently \>1.5 mg/dL
* Macroalbuminuria \>300 mg/24h
* Baseline Hb \<12 gm/dL in women, \<13 gm/dL in men
* Baseline liver function tests outside normal range
* Untreated proliferative retinopathy
* Positive pregnancy test, intent for pregnancy, male's intent to procreate, unwilling to use effective contraception, breast feeding
* Previous transplant or PRA reactivity \>80%
* Insulin requirement \>0.7 IU/kg/day
* HbA1c \>12%
* Hyperlipidemia (fasting cholesterol \>130 mg/dL or fasting triglycerides \>200 mg/dL
* Medical condition requiring chronic use of steroids
* Use of Coumadin or other antiplatelet or anticoagulant therapy, or PT-INR \>1.5
* Factor V deficiency
* Smoking tobacco
* Addison's disease
* Allergy to radiographic contrast material
* Symptomatic cholecystolithiasis
* Acute or chronic pancreatitis
* Symptomatic peptic ulcer disease
* Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with medication absorption
* Treatment with antidiabetic medication other than insulin within 4 weeks of enrollment
* Use of any study medication within 4 weeks of enrollment
* Received live attenuated vaccine(s) within 2 months of enrollment
* Any medical condition that, in the opinion of the investigator, might interfere with safe participation