Regulation of Endogenous Glucose Production by Brain Insulin Action in Insulin Resistance

Inclusion Criteria: 1. Men and women, aged 18 to 60 years 2. Body mass index \>30 kg/m2 3. Hemoglobin in the normal range. 4. Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test 5. Women of reproductive age should be on contraception (oral contraceptive pill or intra-uterine device/coil) for at least 2 months prior to and after the study. Exclusion Criteria: 1. Study participant with a history of hepatitis/hepatic disease that has been active within the previous two years. 2. Any current or previous history of biliary disease (including gall stones, biliary atresia and cholecystitis) or pancreatitis. 3. Any current or previous history of endocrine disease, dyslipidemia or malignancy 4. Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr \> 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hyper/ hypotension (sitting diastolic BP \> 100 or systolic \> 180 or systolic BP\<100) or proliferative retinopathy 5. Use of immunosuppressive agents at any time during the study 6. Allergy to any study medication 7. Pregnancy or breastfeeding 8. Heavy smoker 9. Prior nasoduodenal tube insertion under fluoroscopic guidance. 10. Fasting blood glucose \> 6.0 mmol/l or known diabetes. 11. Any history of a myocardial infarction or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on electrocardiogram, unstable angina, or decompensated heart failure. 12. Any nasal pathology likely to affect absorption of insulin or insertion of nasoduodenal tube. 13. Any laboratory values: aspartate transaminase \> 2x upper limit of normal; alanine aminotransferase \> 2x upper limit of normal; thyroid-stimulating hormone \> 6 micro unit/l 14. Current addiction to alcohol or substances of abuse as determined by the investigator. 15. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation 16. Taking any regular prescription or non-prescription medications at the time of the study. Occasional use of medications such as acetoaminophen or Tylenol 1 or any use of natural health products may be permitted at the discretion of the investigator. 17. Will not donate blood three months prior to and three months post study procedures