The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism

Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism and the secretion of various hormone. The effect of intranasal insulin on peripheral metabolism in humans supposedly is mediated by the vagus nerve.

The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and whether vagus nerve stimulation can mimick this effect.

Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism in the mouse model.

The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and energy metabolism. Intranasal insulin can be used in humans to deliver insulin to the brain and studies have shown that intranasal insulin might reduce food intake, lower body weight and modulate muscle glucose and adipose tissue lipid metabolism in himans. These effects are likely mediated by the vagus nerve as skeletal muscle insulin sensitization after intranasal insulin relates to parasympathetic tone activity (Heni et al. Diabetes 2014). Transcutaneous auricular vagus nerve stimulation (taVNS) activates non-invasively the sensory branches of the vagus nerve and is applied in humans as adjuvant treatment in drug-resistant epilepsy (Frangos et al. 2015). Thereby it can be used to examine whether the vagus nerve indeed mediates brain insulin signals to the periphery.

Here we aim to investigate the effects of intranasal insulin on hepatic glucose, lipid and energy metabolism. We further aim to test whether taVNS can mimick intranasal insulin effects on peripheral metabolism in humans.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 30 and ≤ 70 years
* balanced gender ratio (50: 50)
* BMI 20-25 kg/m² (normal weight subjects)
* BMI 25-35 kg/m² (obese subjects)

Exclusion Criteria:

* acute illness within the last 2 weeks before the examination
* autoimmune diseases and disorders immune- compromised (leukocytes \<5000/μl)
* renal insufficiency (creatinine\> 1.5 mg / dl)
* heart disease, condition after heart attack
* anemia (Hb \<12 g / l, controls at each examination), blood donation within 4 weeks before the examination
* participation in another study within 2 months before the examination
* wear a metal or magnetic objects on or in the body
* claustrophobia
* use of immunomodulatory drugs (cortisol, antihistamines, aspirin)
* thyroid disease
* taking glitazones and insulin therapy
* pregnancy, lactation, menstruation
* cigarette smoking, use of alcohol or drugs, psychiatric disorders
* risk for / or manifest AIDS (HIV) or hepatitis B or C
* liver disease is not attributed to the existence of a non-alcoholic steatosis
* night shift work or circumstances, which do not allow the normal day-night rhythm
* bleeding disorders or disorders in wound healing
* hypersensitivity to local anesthetics
* malignant cancer
* heart rhythm disorders
* polyneuropathy