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This study compares the effect of insulin given as a nasal spray with a placebo. Insulin is a chemical messenger (hormone) in the body that controls fat (triglyceride) levels in the blood by controlling the amount of fat made by the liver and gut. Recent research suggests that insulin may work through the brain. The investigators hypothesize that preferential delivery of insulin into the brain, through nasal spray of the hormone, may affect the amount of fats made by the liver and gut.
Each subject will be studied twice 4-6 weeks apart in random order in this single blinded study. In study A they will receive a single dose of insulin 40 IU through nasal spray. In study B they will receive placebo. On the day of the study subjects will drink regular liquid nutrient formula to maintain a constant fed state. A pancreatic clamp (octreotide with replacement glucose, insulin and growth hormone) will be started at 7am. From 9am a regular infusion of a stable isotope tracer will be started together with nasal spray of either insulin/placebo. Regular blood samples will be drawn to assess lipoprotein kinetics.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Insulin | Experimental | Nasal spray, insulin 40 IU, single dose |
|
| Placebo | Placebo Comparator | Nasal spray, placebo, single dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Insulin | Drug | Insulin 40 IU, nasal spray, single dose |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Triglyceride-rich lipoprotein apolipoprotein B100 production rate | Triglyceride-rich lipoprotein apolipoprotein B100 production rate will be measured following nasal spray of insulin or placebo | 10 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Triglyceride-rich lipoprotein apolipoprotein B48 production rate | Triglyceride-rich lipoprotein apolipoprotein B48 production rate will be measured following nasal spray of insulin or placebo | 10 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gary F Lewis, MD | University Health Network, Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tornto General Hospital, UHN | Toronto | Ontario | M5G 1L7 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28751575 | Derived | Xiao C, Dash S, Stahel P, Lewis GF. Effects of Intranasal Insulin on Triglyceride-Rich Lipoprotein Particle Production in Healthy Men. Arterioscler Thromb Vasc Biol. 2017 Sep;37(9):1776-1781. doi: 10.1161/ATVBAHA.117.309705. Epub 2017 Jul 27. |
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| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| Drug |
Placebo, nasal spray, single dose |
|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |