Influence of Central Nervous Insulin Sensitivity on Insulin Secretion
- Conditions
- Insulin Secretion
- Interventions
- Drug: Placebo
- Registration Number
- NCT02870361
- Lead Sponsor
- University Hospital Tuebingen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 15
- HbA1c ≤6.0%
- normal glucose tolerance during 75g oral glucose tolerance test (OGTT)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Insulin nasal spray intranasal insulin 160 Units of human insulin as nasal spray Placebo nasal spray Placebo Nasal spray containing placebo solution
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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.
Trial Locations
- Locations (1)
University of Tuebingen, Department of Internal Medicine IV
🇩🇪Tübingen, Germany