Influence of Central Nervous Insulin Action on Insulin Sensitivity of Peripheral Organs in Lean Versus Overweight Humans

Research in animals and first experiments in humans indicate that insulin action in the brain regulates peripheral insulin sensitivity. One major organ might be the liver. Previous studies in humans showed that the human brain is an insulin sensitive organ in lean but not in overweight/obese persons. Therefore, this study will include lean versus overweight/obese persons.

In this study, insulin action will be introduced by intranasal insulin administration in lean and overweight humans. As a control, placebo spray will be administered. To mimick the known spill over of small amounts of intranasal insulin into circulation, a small bolus of insulin will be administered over 15 minutes following placebo spray application.

Peripheral insulin sensitivity will be assessed by hyperinsulinemic-euglycemic glucose clamp and glucose uptake and endogenous glucose production will be assessed by tracer dilution technique. Autonomous nervous system activity will be addressed by heart rate variability. Involved brain areas will be addressed by fMRI before and after nasal insulin application.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance
• Intervention / Treatment: Drug: human insulin

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • University of Tuebingen, Department of Internal Medicine IV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male volunteers (lean or overweight/obese)
• HbA1c <6.0%
• Age between 18 and 40 years
• healthy as assessed by physician
• Understanding the explanations about the study and instructions

Exclusion Criteria:

• non-removable metal parts in or on the body
• Persons with reduced temperature sensation and / or increased sensitivity to warming of the body
• Cardiovascular disease can not be excluded, such as evident coronary heart disease, congestive heart failure NYHA greater than 2, history of coronary artery disease
• History of stroke
• Persons with a hearing disorder or increased sensitivity to loud noises
• People with claustrophobia
• Subjects in which less than 3 months have passed since surgery
• Simultaneous participation in other studies
• Acute disease or infection within the last 4 weeks
• Neurological and psychiatric disorders
• Subjects with hemoglobin Hb <13g / dl
• Heparin-induced thrombocytopenia people with a (HIT) in prehistory
• Allergies to any of the used solutions/devices

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: insulin nasal spray; 160 Units of human insulin as nasal spray	Drug: human insulin
PLACEBO_COMPARATOR: placebo nasal spray; Nasal spray containing placebo solution	Drug: human insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glucose infusion rate during hyperinsulinemic euglycemic glucose clamp from before to after nasal spray application in lean persons		Change from 70-90 min (before spray) to 170-210 min and to 280-300 min
Change in endogenous glucose production from before to after nasal spray application in lean persons	Will be assessed by tracer dilution technique.	Change from 70-90 min (before spray) to 170-210 min and to 280-300 min
Differences in insulin response between lean and overweight persons	Will be assessed as plasma insulin and C-peptide concentrations.	up to 210 minutes post nasal spray administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autonomous nervous system activity	Will be assessed by analysis of heart rate variability.	baseline, 70-90 min, 170-210 min and 280-300 min
Regional brain insulin sensitivity	Will be assessed on an additional study day by fMRI before and after intranasal insulin administration	30 min

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Andreas Fritsche, Prof. Dr., University Hospital Tuebingen

Publications and helpful links

General Publications

• Heni M, Wagner R, Kullmann S, Gancheva S, Roden M, Peter A, Stefan N, Preissl H, Haring HU, Fritsche A. Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men. Diabetes. 2017 Jul;66(7):1797-1806. doi: 10.2337/db16-1380. Epub 2017 Feb 7.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: March 24, 2015
• First Submitted That Met QC Criteria: June 8, 2015
• First Posted (ESTIMATE): June 11, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): January 8, 2016
• Last Update Submitted That Met QC Criteria: January 7, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Intranasal insulin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 402/2014B01