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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Somatropin; Other: Ketone bodies

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; 12 hours of fasting
Experimental: GH infusion; 12 hours of fasting	Drug: Somatropin; Somatropin infusion (Genotropin®)
Experimental: GH and ketone bodies infusion; 12 hours of fasting	Drug: Somatropin; Somatropin infusion (Genotropin®); Other: Ketone bodies; ketone bodies infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin and growth hormone signaling, expressed as CHANGE in phosphorylation of intracellular target proteins in muscle- and fat-tissue.	Change in phosphorylation of target proteins using Western Blotting (WB)	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose metabolism	Change in glucose metabolism assessed by tracer kinetics on every study day.	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.
Insulin and growth hormone signaling, expressed as CHANGE in messenger ribonucleic acid (mRNA) expression of target genes in muscle- and fat-tissue.	Change in mRNA expression of target genes using Polymerase Chain Reaction (PCR).	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.
Investigation of the balance in the autonomic nervous system	Heart rate variability (the study of beat-to-beat fluctuations in heart rate).	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.

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Jens Otto L. Jørgensen, Professor, Aarhus University / Aarhus University Hospital; Study Director: Jens Otto L. Jørgensen, Professor, Aarhus University / Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: January 7, 2016
• First Submitted That Met QC Criteria: January 11, 2016
• First Posted (Estimate): January 14, 2016

Study Record Updates

• Last Update Posted (Actual): November 1, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: Ketone8000