Abnormalities in the Effects of Insulin and Exercise on Glucose- and Lipid Metabolism in Obesity and Type 2 Diabetes

Summary

Type 2 diabetes are characterized by insulin resistance in skeletal muscle. Insulin resistance plays a major role for the increased risk of heart disease seen in type 2 diabetes. No specific treatment of insulin resistance is currently available, except from increased physical activity and weight-loss.

Insulin resistance is characterized by abnormalities in the use of glucose and fat in the muscle, and is associated with abnormal function and content of mitochondria (the power houses of our cells) as well as increased levels of fat within the muscle.

The investigators believe that abnormalities in the use of glucose and fat in muscle cells in response to insulin and exercise can explain why insulin resistance is associated with abnormal function and content of mitochondria and an increased amount of fat in skeletal muscle of patients with type 2 diabetes and individuals with obesity.

The major purpose of our project is, therefore, to investigate the effect of insulin in physiological concentrations and the effect of both acute exercise and 8 weeks of high intensity interval exercise-training on

1. insulin sensitivity, body composition, cardiorespiratory fitness and energy metabolism,
2. insulin signaling, mitochondrial dynamics and mitophagy in skeletal muscle

4\) regulators of storage of fat into lipid droplets and their interaction with mitochondria in skeletal muscle 5) acetylation and phosphorylation of enzymes (proteins) in major metabolic and signaling pathways, as well as 6) transcriptional and signalling networks regulating mitochondrial biogenesis and substrate metabolism.

The effects of insulin in physiological concentrations and a novel exercise-intervention combining biking and rowing will be studied in a comprehensive study of obese patients with type 2 diabetes compared with weight-matched obese and lean healthy controls.

The effects of insulin before and after 8 weeks HIIT on whole-body metabolism will be evaluated by measurement of maximal oxygen consumption, and well-known methods to determine insulin-stimulated glucose utilization, insulin secretion and use of glucose and fat. Skeletal muscle and fat tissue samples obtained under these conditions will be used for assessment of tissue-levels of specific sets of genes and enzymes known to be involved in insulin action, quality and size of mitochondria, and storage of fat into lipid droplets and their interaction with mitochondria.

This project is expected to provide important and novel insight into the causal relationship between insulin resistance, accumulation of fat and abnormal content and function of mitochondria in skeletal muscle in type 2 diabetes.

The investigators ultimately expect that our findings will help us to identify novel molecules or enzymatic pathways, which can be used to develop drugs that can enhance or mimic the effects of insulin and exercise, and hence be used in the prevention and treatment of type 2 diabetes and heart disease.

Conditions

• Type2 Diabetes
• Insulin Resistance

Interventions

OTHER

High intensity interval training

See under arm description.

Sponsors & Collaborators

• Department of Sports Science and Clinical Biomechanics, University of Southern Denmark

  collaborator UNKNOWN

• Odense University Hospital

  lead OTHER

Principal Investigators

• Kurt Højlund, Professor, DMSc, PhD, MD · Department of Endocrinology, Odense University Hospital

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

40 Years

Max Age

65 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-02-26

Primary Completion

2021-11-12

Completion

2021-11-12

Countries

• Denmark

Study Locations