A Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Activity of Very Low Dose-Glucagon in Subjects With Type 1 Diabetes Mellitus

Inclusion Criteria: 1. Males or females, 18 to 55 years of age, requiring daily insulin for the management of type 1 diabetes mellitus for \>10 years 2. On a stable basal insulin regimen using CSII therapy ("stable" defined as total daily dose of insulin not changed by more than ± 20% for 2 months prior to screening) 3. Glycosylated hemoglobin (HbA1c) ≤8.0% 4. Total daily insulin requirement of ≤1 unit/kg of body weight 5. Fasting C-peptide level of \<1.0 ng/mL (\<330 pmol/L) (may be done at screening or may be taken from subject's medical record if performed within the past 12 months) 6. Body mass index (BMI) ≤25.5 kg/m2 and body weight over past 6 months within ± 5% 7. Hemoglobin, hematocrit, and platelets within normal limits; no clinically significant abnormality of white blood cells (WBC) or differential 8. Serum chemistry results within normal limits except for liver enzymes \[aspartate transaminase (AST) and alanine transaminase (ALT)\] which must be within 2.5 times upper limit of normal (ULN) and creatinine which must be \<1.6 mg/dL 9. Normal thyroid stimulating hormone 10. No history of HIV infection and negative results for hepatitis B and C 11. Negative serum pregnancy test, non-lactating, and using adequate contraception, if female and of child bearing potential (intact uterus and pre-menopausal) 12. Medications for the treatment of high blood pressure and/or dyslipidemia are allowed if regimen stable for 2 months prior to screening 13. Medically stable as determined by history and physical examination, including vital signs 14. Electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality 15. Willing and able to give written informed consent Exclusion Criteria: 1. Participation in a clinical trial with or use of an investigational agent within 30 days of Study Visit 1. 2. History of atherosclerosis including coronary artery disease, angina pectoris, myocardial infarction, cerebrovascular accident, or transient ischemic attacks 3. History or symptoms of pheochromocytoma 4. History of any malignancy within 3 years except for basal cell skin cancer 5. Active infection, drug or alcohol abuse, eating disorder, or psychiatric disorder 6. Concomitant medications: systemic or potent topical steroids or medications that may affect blood glucose, e.g., sulfonylureas, alpha-glucosidase inhibitors, biguanides, meglitinides, thiazolidinediones 7. Any condition which increases the risk of participation in the trial in the opinion of the investigator -