The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism

Diabetes Clinical Trial

— Centrin  

Official title:

The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01479075
• Other study ID #: Centrin
• Status: Completed
• Phase: Phase 4
• Start date: August 2011
• Est. completion date: June 2014

Study information

• Verified date: June 2023
• Source: German Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Insulin Resistance

Intervention

Drug:
• intransal insulin
4x 40mU intranasal insulin
• Placebo

Device:
• taVNS

• sham stimulation

Locations

Country	Name	City	State
Germany	German Diabetic Center	Düsseldorf	Nordrhein- Westfalen

Sponsors (1)

Lead Sponsor	Collaborator
German Diabetes Center

Country where clinical trial is conducted

Germany, 

References & Publications (3)

Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6. — View Citation

Gancheva S, Koliaki C, Bierwagen A, Nowotny P, Heni M, Fritsche A, Haring HU, Szendroedi J, Roden M. Effects of intranasal insulin on hepatic fat accumulation and energy metabolism in humans. Diabetes. 2015 Jun;64(6):1966-75. doi: 10.2337/db14-0892. Epub — View Citation

Heni M, Wagner R, Kullmann S, Veit R, Mat Husin H, Linder K, Benkendorff C, Peter A, Stefan N, Haring HU, Preissl H, Fritsche A. Central insulin administration improves whole-body insulin sensitivity via hypothalamus and parasympathetic outputs in men. Diabetes. 2014 Dec;63(12):4083-8. doi: 10.2337/db14-0477. Epub 2014 Jul 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity	Assessment of insulin sensitivity with gold standard methods	6 months
Secondary	Energy metabolism	Energy metabolism is assessed from gold standard methods	6 months