Interplay Between Interleukin-6 and Glucagon in the Regulation of Human Amino Acid and Protein Homeostasis

N/ACompletedNCT06721910

University Hospital, Basel, Switzerland26 enrolled

Overview

The goal of this proof-of-concept study is to learn if interleukin-6 changes the effect of glucagon in healthy volunteers. The main question it aims to answer is: Does IL-6 influence how effectively glucagon lowers the concentration of amino acids in blood? Researchers will compare the infusion of normal saline and a blocker of the receptor for interleukin-6 to see if blocking interluekin-6 changes how effectively glucagon lowers the concentration of amino acids in blood. Participants will be asked to * receive either an infusion of normal saline or the interleukin-6 receptor blocker * participate in a study visit three weeks later at which they will receive infusions of hormones and amino acids to mimic the concentrations of the hormones insulin and glucagon during fasting or fed conditions * labelled glucose, glycerol and amino acids will also be infused continuously to track the fate of these molecules * during the hormone infusions blood samples will be taken repeatedly

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Healthy Glucagon Resistance Amino Acid Change

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria: * Age 18 to 50 years * BMI 18.5 - 25 kg/m2 * Stable body weight in the past 6 months before study initiation * Women should be anovulatory on non-cyclic hormone replacement or hormonal contraception Exclusion criteria: * Previous medical history for any chronic condition in the last three months, active disease or abnormal physical examination as verified by a qualified physician * Body weight unstable in the past 6 months * Use of tobacco/nicotine * Alcohol consumption \>30g/day * Participation in an investigational drug trial within the past two months * Current intake of any drugs (prescribed, over the counter or recreational) * Known allergy to tocilizumab * Pregnant or lactating women, * Inability or unwillingness to provide informed consent

Outcomes

Primary Outcomes

Change in maximum glucagon-induced reduction in total plasma amino acid concentrations

Time frame: At visit 2 during high glucagon phase (80-120 minutes)

Secondary Outcomes

AUC of total amino acids

Time frame: At visit 2 during high glucagon phase (80-120 minutes)

rate of phenylalanine oxidation

Time frame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)

urea concentrations

Time frame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)

rate of gluconeogenesis from amino acids

Time frame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)

fractional synthesis rate of plasma proteins

Time frame: At visit 2 (60, 180, 300 minutes)

Amino acid uptake by PBMCs ex vivo

Time frame: At visit 1 and visit 2 (-120 minutes)

Change in fractional synthesis rate of lipoproteins

Time frame: At visit 2 (60, 180, 300 minutes)

Cytokine plasma concentrations (IL-6, IL-1RA, TNF-alpha, IL-8, IL-10, CRP)

Time frame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)

Plasma concentrations of insulin, c-peptide, glucagon, GH, IGF-1, cortisol, catecholamines, fT4, fT3, FGF21, follistatin, AGPTL4, ketones

Time frame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)

Energy expenditure kcal/24 hours

Time frame: At visit 2 (40, 160, 280 minutes)

Respiratory exchange rate

Time frame: At visit 2 (40, 160, 280 minutes)

Oxygen consumption (VO2 ml/minutes)

Time frame: At visit 2 (40, 160, 280 minutes)

Carbondioxid production (VCO2 ml/minutes)

Time frame: At visit 2 (40, 160, 280 minutes)

Body composition (lean body mass kg)

Time frame: At visit 1 and 2 (-120 minutes)

Body composition (fat bodymass kg)

Time frame: At visit 1 and 2 (-120 minutes)

Blood pressure systolic

Time frame: At visit 2 (-120 minutes)

Blood pressure diastolic

Time frame: At visit 2 (-120 minutes)

Heart rate

Time frame: At visit 2 (-120minutes)

Interplay Between Interleukin-6 and Glucagon in the Regulation of Human Amino Acid and Protein Homeostasis

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes