Insulin Secretion
Conditions
Brief summary
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.
Interventions
DRUGintranasal insulin
DRUGPlacebo
Sponsors
University Hospital Tuebingen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Correlation with brain insulin sensitivity | 15-30 minutes post insulin nasal spray | 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) |
| Differential effects in lean and overweight | 0-10 min during hyperglycemic clamp and 10-90 min during hyperglycemic clamp | 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. |
| Correlation with autonomous nervous system activity | 10 - 150 minutes post nasal spray | 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). |
| Peripheral insulin sensitivity | 10-90 min and 70-90 min during hyperglycemic clamp | Effect of nasal insulin versus placebo on peripheral insulin sensitivity assessed by hyperglycemic hyperinsulinemic clamp. |
Countries
Germany
Outcome results
None listed