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The Role of TBC1D4 in Exercise- and Insulin-induced Glucose Metabolism in Human Skeletal Muscle

NCT04170972 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 16

Last updated 2022-01-06

No results posted yet for this study

Summary

Recently a common Greenlandic nonsense p.Arg684erTer variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 was discovered. The variant has an allele frequency of 17%. Homozygous carriers of this TBC1D4 variant have impaired glucose tolerance and a 10-fold enhanced risk of developing type 2 diabetes (T2D). The investigators propose to carry out comprehensive metabolic phenotyping of adult Inuits carrying zero or two alleles of the TBC1D4 variant. The investigators hypothesise that regulation of TBC1D4 in skeletal muscle is pivotal in regulating glucose uptake during exercise, during physiological insulin stimulation, and for the ability of an acute bout of exercise to improve insulin sensitivity to regulate glucose metabolism in humans.

The overall aims in the present project are to:

1. Determine whether the TBC1D4 p.Arg684Ter variant affects the regulation of glucose uptake in skeletal muscle during exercise and during physiological insulin stimulation.
2. Determine the effect of the TBC1D4 p.Arg684Ter variant for the ability of acute exercise to insulin sensitize skeletal muscle to regulate glucose metabolism.
3. Define the metabolic pathways affected by the p.Arg684Ter variant in order to identify causal factors responsible for the diabetic phenotype of Inuit carriers.

The knowledge generated will contribute to additional explanatory clues to the increased frequency of T2D in the carriers.

Conditions

  • Exercise
  • Insulin Sensitivity
  • Skeletal Muscle

Interventions

OTHER

Acute exercise

One hour of acute one-legged knee-extensor exercise followed by 3 hours recovery and 2 hours insulin (1.5 mU/min/kg) stimulation.

Sponsors & Collaborators

  • University of Copenhagen

    lead OTHER

Study Design

Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
20 Years
Max Age
70 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2017-10-17
Primary Completion
2019-05-01
Completion
2019-09-01

Countries

  • Denmark

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04170972 on ClinicalTrials.gov