Regulation of Endogenous Glucose Production by Brain Insulin Action

• Status: Completed
• Trial end date: 2014-07-01
• Target enrollment: 0
• Participant gender: All

Summary

It is well known that the hormone insulin lowers blood glucose in part by acting directly on the liver and reducing hepatic glucose production. Animal studies have shown that the hormone insulin can act on the brain to indirectly lower glucose production by the liver. We aim to test whether this is true in humans by giving insulin intranasally. It has previously been shown that a nasal spray can deliver insulin directly to the brain without affecting circulating insulin concentration.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Health Network, Toronto
• Treatments: Insulin; Insulin Lispro; Insulin, Globin Zinc

Criteria

Inclusion Criteria:

1. Men and women, aged 18 to 60 years

2. Body mass index 20-27.

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.

Volunteers who have taken part in the study with the previously approved protocol will be eligible to participate in the amended study, if they provide their informed consent

Exclusion Criteria:

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 MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, 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: AST > 2x ULN; ALT > 2x ULN TSH > 6 mU/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