Substrate Metabolism, Growth Hormone Signaling (GH), and Insulin Sensitivity During GH and Ketone Bodies Infusion

Not Applicable

Completed

• Conditions: Healthy
• Interventions: Drug: Somatropin; Other: Ketone bodies

• Registration Number: NCT02655263
• Lead Sponsor: University of Aarhus

Brief Summary

Background: Humans naturally produce ketone bodies under daily living conditions. The main ketone bodies are two functioning acids, beta-hydroxybutyric acid (3-OHB) and acetoacetate, and the pH-neutral, but odorous, acetone. In the fed state, level of 3-OHB is suppressed to an almost unmeasurable level while, in the fasted state, it rises to 0.1-0.5 millimoles (mM). Main regulation of ketone synthesis is the abundance of sugars and resulting adaptations in insulin secretion. Thus, ketone bodies are formed when sugar is not readily available and insulin is suppressed. This picture is, to a certain degree, seen in acute inflammatory states and, indeed, during starvation, where level of 3-OHB increases to 5-8 mM.

Hypothesis:

1. Ketone bodies changes the insulin sensitivity and substrate metabolism in human subjects

2. Ketone bodies changes the GH signaling in muscle and adipose tissue

Aim: The investigators wish to provide knowledge on changes in metabolites and shift in signaling pathways and insulin sensitivity during GH infusion and concomitant ketone bodies infusion among healthy subjects.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-01-07
• Study First Submitted QC: 2016-01-11
• Study First Posted: 2016-01-14
• Status Verified: 2017-10
• Primary Completion: 2017-10
• Study Completion: 2017-10
• Last Update Submitted: 2017-10-31
• Last Update Posted: 2017-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

Inclusion Criteria

• healthy men
• written consent
• body mass index (BMI) 18.5 - 25
• age 20-50 years

Exclusion Criteria

• any kind of disease
• regular medication

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
GH infusion	Somatropin	12 hours of fasting
GH and ketone bodies infusion	Ketone bodies	12 hours of fasting
GH and ketone bodies infusion	Somatropin	12 hours of fasting

Primary Outcome Measures

Name	Time	Method
Insulin and growth hormone signaling, expressed as CHANGE in phosphorylation of intracellular target proteins in muscle- and fat-tissue.	Muscle and fat biopsies obtained at t1= 9.00 am (60 min) and t2=12.30 am (270 min) on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days	Change in phosphorylation of target proteins using Western Blotting (WB)

Secondary Outcome Measures

Name	Time	Method
Glucose metabolism	Change in glucose metabolism using glucose tracer from t=0 min - 360 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days.	Change in glucose metabolism assessed by tracer kinetics on every study day.
Insulin and growth hormone signaling, expressed as CHANGE in messenger ribonucleic acid (mRNA) expression of target genes in muscle- and fat-tissue.	Muscle and fat biopsies obtained at t1= 9.00 am (60 min) and t2=12.30 am (270 min) on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days.	Change in mRNA expression of target genes using Polymerase Chain Reaction (PCR).
Investigation of the balance in the autonomic nervous system	Measurement of heart rate variability at t1=10.30 am(150 min) and 12.30 am (270 min) on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days.	Heart rate variability (the study of beat-to-beat fluctuations in heart rate).

Trial Locations

Locations (1)

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark