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Insulin resistance is a central pathophysiological component of type 2 diabetes and is associated with a high risk of cardiovascular disease. The tissue in which it manifests are mainly muscle, liver, and adipose tissue. Since the transport of glucose to the brain is independent of insulin, this organ has traditionally not been studied in this regard. In animal experiments, however, knockout of the insulin receptor in the brain leads to obesity and peripheral insulin resistance. This finding of insulin action in the brain could also be confirmed in human studies.
The investigators intend to investigate whether central nervous insulin action affects insulin secretion in humans. For this purpose, nasal insulin and placebo are administered 15 minutes before a hyperglycemic hyperinsulinemic clamps, which stimulate insulin secretion. Insulin sensitivity of the brain is measured by a an established protocol with functional magnetic resonance imaging before and after nasal insulin administration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Insulin nasal spray | Active Comparator | 160 Units of human insulin as nasal spray |
|
| Placebo nasal spray | Placebo Comparator | Nasal spray containing placebo solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| intranasal insulin | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin secretion assessed as serum C-peptide levels during a hyperglycemic clamp | 0-10 min during hyperglycemic clamp and 10-90 min during hyperglycemic clamp |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation with brain insulin sensitivity | Correlation of regional brain insulin sensitivity with the change of pancreatic insulin secretion due to central action of insulin. Changes in regional cerebral blood flow from before to after intranasal insulin administration will be assessed by functional magnetresonance imaging (fMRI) | 15-30 minutes post insulin nasal spray |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Martin Heni, MD | University Hospital Tuebingen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Tuebingen, Department of Internal Medicine IV | Tübingen | 72076 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31689708 | Derived | Heni M, Wagner R, Willmann C, Jaghutriz BA, Vosseler A, Kubler C, Hund V, Scheffler K, Peter A, Haring HU, Preissl H, Kullmann S, Fritsche A. Insulin Action in the Hypothalamus Increases Second-Phase Insulin Secretion in Humans. Neuroendocrinology. 2020;110(11-12):929-937. doi: 10.1159/000504551. Epub 2019 Nov 5. |
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|
| Differential effects in lean and overweight | Differences in the effect of nasal insulin versus placebo on C-peptide levels during a hyperglycemic clamp between lean and overweight men will be assessed. | 0-10 min during hyperglycemic clamp and 10-90 min during hyperglycemic clamp |
| Correlation with autonomous nervous system activity | Correlation of the change in pancreatic insulin secretion by central insulin action with the simultaneous change of the autonomous nervous system (measured by heart rate variability). | 10 - 150 minutes post nasal spray |
| Peripheral insulin sensitivity | Effect of nasal insulin versus placebo on peripheral insulin sensitivity assessed by hyperglycemic hyperinsulinemic clamp. | 10-90 min and 70-90 min during hyperglycemic clamp |