The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism
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.
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