Influence of Central Nervous Insulin Sensitivity on Insulin Secretion

Study Overview
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Brief Summary
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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.

Official Title
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Einfluss Der zentralnervösen Insulinsensitivität Auf Die Insulinsekretion

Conditions
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Insulin Secretion

Intervention / Treatment
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* Drug: intranasal insulin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HbA1c ≤6.0% normal glucose tolerance during 75g oral glucose tolerance test (OGTT) Exclusion Criteria: Not removable metal parts in or on the body manifest cardiovascular disease claustrophobia recent surgery (less than 3 months) Simultaneous participation in other studies Acute disease or infection within the last 4 weeks neurological and psychiatric disorders treatment with centrally acting drugs hemoglobin Hb <13g / dl Hypersensitivity to any of the substances used

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin nasal spray<br>160 Units of human insulin as nasal spray | Drug: intranasal insulin<br> <br> |
| Placebo Comparator: Placebo nasal spray<br>Nasal spray containing placebo solution | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 |