Adrenergic System in Islet Transplantation

Inclusion Criteria: GROUP 1 1. Male and female subjects age 21 to 65 years of age. 2. Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol. 3. Clinical history compatible with type 1 diabetes with onset of disease at \< 40 years of age and insulin-dependent for \> 10 years at the time of islet transplantation \> 6 months before study. 4. Stable islet graft function defined by C-peptide \> 0.5 ng/ml and insulin-independent or insulin-dependent with daily insulin requirement \< 0.2 units/kg•d to maintain HbA1c \< 7.0%. 5. Use of standard immunosuppression consisting of tacrolimus with or without sirolimus or mycophenolic acid. Substitutions of tacrolimus with cyclosporine, and of sirolimus or mycophenolic acid with azathioprine are permissible if stable for over 3 months. Prednisone is allowable if no more than 5 mg daily. Exclusion Criteria: GROUP 1 1. BMI ≥ 30 kg/m2. 2. Insulin requirement of ≥ 0.2 units/kg•day. 3. HbA1c ≥ 7.0%. 4. Uncontrolled hypertension: systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg. 5. History of cardiovascular disease, including coronary artery, cerebrovascular or peripheral vascular disease, or current use of β-blocker therapy. 6. Bronchial asthma. 7. Abnormal kidney function: Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73 m2. 8. Abnormal liver function: persistent elevation of liver function tests \> 1.5 times the upper limit of normal. 9. Untreated hypothyroidism, Addison's disease, or Celiac disease. 10. Anemia: baseline hemoglobin concentration \< 11 g/dl in women and \< 12 g/dl in men. 11. Presence of a seizure disorder not related to prior severe hypoglycemia. 12. Use of glucocorticoids greater than 5 mg of prednisone daily, or an equivalent physiologic dose of hydrocortisone. 13. For female participants of child-bearing potential: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of study participation. Oral contraceptives, intra-uterine devices, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable. 14. Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment. 15. Use of any investigational agents within 4 weeks of enrollment. 16. Any medical condition that, in the opinion of the PI, will interfere with the safe completion of the study Inclusion Criteria GROUP 2 1. Male and female subjects age 21 to 65 years of age. 2. Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol. 3. Clinical history compatible with type 1 diabetes with onset of disease at \< 40 years of age and insulin-dependent for \> 10 years at the time of islet transplantation \> 6 months before study. 4. Stable islet graft function defined by C-peptide \> 0.5 ng/ml and insulin-independent or insulin-dependent with daily insulin requirement \< 0.2 units/kg•d to maintain HbA1c \< 7.0%. 5. Use of standard immunosuppression consisting of tacrolimus with or without sirolimus or mycophenolic acid. Substitutions of tacrolimus with cyclosporine, and of sirolimus or mycophenolic acid with azathioprine are permissible if stable for over 3 months. Prednisone is allowable if no more than 5 mg daily. Exclusion Criteria: GROUP 2 1. BMI ≥ 30 kg/m2. 2. Insulin requirement of ≥ 0.2 units/kg•day. 3. HbA1c ≥ 7.0%. 4. Uncontrolled hypertension: systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg. 5. Active cardiovascular disease, including coronary artery, cerebrovascular or peripheral vascular disease. 6. Abnormal kidney function: eGFR \< 60 ml/min/1.73 m2. 7. Abnormal liver function: persistent elevation of liver function tests \> 1.5 times the upper limit of normal. 8. Untreated hypothyroidism, Addison's disease, or Celiac disease. 9. Anemia: baseline hemoglobin concentration \< 11 g/dl in women and \< 12 g/dl in men. 10. Presence of a seizure disorder not related to prior severe hypoglycemia. 11. Use of glucocorticoids greater than 5 mg of prednisone daily, or an equivalent physiologic dose of hydrocortisone. 12. For female participants of child-bearing potential: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of study participation. Oral contraceptives, intra-uterine devices, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable. 13. Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment. 14. Use of any investigational agents within 4 weeks of enrollment. 15. Any medical condition that, in the opinion of the PI, will interfere with the safe completion of the study Inclusion Criteria GROUP 3 Patients who meet all of the following criteria are eligible for participation in Group 3 of this study: 1. Male and female subjects age 21 to 65 years of age. 2. Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol. 3. Clinical history compatible with total pancreatectomy and autologous islet transplantation \> 6 months before study. 4. Stable islet graft function defined by C-peptide \> 0.5 ng/ml and insulin-independent or insulin-dependent with daily insulin requirement \< 0.2 units/kg•d to maintain HbA1c \< 7.0%. Exclusion Criteria: GROUP 3 1. BMI ≥ 30 kg/m2. 2. Insulin requirement of ≥ 0.2 units/kg•day. 3. HbA1c ≥ 7.0%. 4. Uncontrolled hypertension: systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg. 5. Active cardiovascular disease, including coronary artery, cerebrovascular or peripheral vascular disease. 6. Abnormal kidney function: eGFR \< 60 ml/min/1.73 m2. 7. Abnormal liver function: persistent elevation of liver function tests \> 1.5 times the upper limit of normal. 8. Anemia: baseline hemoglobin concentration \< 11 g/dl in women and \< 12 g/dl in men. 9. Presence of a seizure disorder not related to prior severe hypoglycemia. 10. Use of glucocorticoids greater than 5 mg of prednisone daily, or an equivalent physiologic dose of hydrocortisone. 11. For female participants of child-bearing potential: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of study participation. Oral contraceptives, intra-uterine devices, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable. 12. Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment. 13. Use of any investigational agents within 4 weeks of enrollment. 14. Any medical condition that, in the opinion of the PI, will interfere with the safe completion of the study