Insulin Sensitivity
Conditions
Keywords
brain insulin action, autonomic nervous system, physical activity, immune system
Brief summary
The goal of this clinical trial is to clarify the interaction of central insulin action and physical activity with the immune system. Therefore, participants will undergo bicycle spiroergometer tests. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray. In another trial (NCT06552130) lean participants already have been tested. Significant effects on circulating cytokines could be identified. In this amendment, overweight persons in which brain insulin resistance is expected will be tested.
Detailed description
This research project aims to investigate if the brain insulin action regulates the immune system via the autonomous nervous system during physical activity and investigate whether participants with overweight respond different compared to lean persons. The lean persons were already studied in another trial (NCT06552130) and this trial serves as an amendment. Insulin action in the brain will be introduced by application of insulin as nasal spray (on one day) versus carrier solution as placebo nasal spray (on another day) in a randomized, blinded fashion. Spray administration will be performed 30 minutes before a 60 min bicycle spiroergometer test at 70 % VO2max that will introduce a postprandial state. On placebo day, the known spillover of tiny amounts of nasal insulin into the systemic circulation will be mimicked by an appropriate i.v. insulin bolus. Using this approach, brain-derived regulation of the immune system including the stimulation of immune cells via cytokines, physical performance, activity of the autonomous nervous system and gene-expression of leukocytes will be examined.
Interventions
Participants will undergo a 60 min bicycle spiroergometer test and intranasal insulin spray. Intranasal insulin will be administered 30 minutes prior to the start of the physical activity.
Participants will undergo a 30 min bicycle spiroergometer test and intranasal placebo spray. To mimic insulin spill-over from nasal spray into systemic circulation, an i.v. insulin bolus of 3 mU × kg-1. will be administered over 15 minutes 30 minutes prior to the start of the physical activity on the placebo spray day. On the insulin spray day a comparable amount of saline will be infused.
Sponsors
University of Ulm
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI \> 28 kg/m2 * no known primary disease * hormonal contraception with a single-phase preparation
Exclusion criteria
* alcohol or drug abuse * At screening: Hb \< 12 g/dl for women and Hb \< 14 g/dl for men * Any (clinical) condition that would endanger participant's safety or question scientific success according to a physician's opinion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immune system activation | 120 minutes | Influence of central nervous insulin action on the activation of the immune system activation by exercise, measured by circulating cytokines and cytokines in the supernatant of stimulated peripheral blood mononuclear cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximal oxygen consumption (VO2max) | 60 minutes | Influence of central nervous insulin action on physical performance measured as VO2 peak during spiroergometry. |
| Heat rate variability | 120 minutes | Influence of central nervous insulin action on the activity of the autonomic nervous system recorded by means of heart rate variability from an electrocardiogram. |
| Corticotropic pituitary axis modulation | 120 minutes | Corticotropic pituitary axis modulation Influence of central nervous insulin action in the activity of the corticotropin pituitary axis during physical activity, measured by cortisol, dehydroepiandrosterone and adrenocorticotropic hormone |
| Leukocyte gene expression | 120 minutes | Influence of central nervous insulin action on the gene expression of leukocytes during physical activity |
| Individual anaerobic threshold | 120 minutes | Influence of central nervous insulin action on physical performance. Individual anaerobic threshold assessed by lactate measurement from venous blood sampling. |
| Catecholamines | 120 minutes | Influence of central nervous insulin action on the activity of the autonomic nervous system recorded by means of measuring catecholamine concentrations from venous blood. |
| Effects on blood coagulation parameters | 120 minutes | Influence of central nervous insulin action and/or physical activity on blood coagulation parameters assessed through global coagulation tests and single coagulation factors. |
Countries
Germany
Contacts
CONTACTMartin Heni, MD
CONTACTSabrina Wangler
PRINCIPAL_INVESTIGATORMartin Heni, MD
University of Ulm
Outcome results
None listed