Skeletal Muscles, Myokines and Glucose Metabolism MYOGLU (MyoGlu)

Skeletal Muscles, Myokines and Glucose Metabolism

Normal glucose uptake and metabolism in skeletal muscles are essential to keep blood glucose within normal range and hence, insulin resistance (possibly mediated by inflammatory processes) in skeletal muscle is a major pathogenic factor in type 2 diabetes. Physical activity seems to be of essential importance in the prevention and treatment of type 2 diabetes. Myokines are proteins secreted from skeletal muscle that can execute important biological functions locally in the muscle (paracrine) or in other organs like the brain, heart and pancreas (endocrine). Evidence suggest that several interleukines and other cytokines are secreted by skeletal muscles. In the present project, the investigators will explore the relation between secreted myokines from muscle cells, insulin resistance and glucose metabolism before and after 12 weeks of exercise intervention. Subjects with normal as well as impaired glucose metabolism will be included in the study.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia; Myokine; Normoglycemia
• Intervention / Treatment: Other: Exercise

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• Age 40-65 years
• Nordic ethnicity

• Non-smoker

  1. Either (participants with impaired glucose metabolism): Body Mass Index (BMI) 27-32 kg/m2 and abnormal glucose metabolism, defined as:

     i. impaired fasting glucose (FPG ≥ 5.6 mmol/L) ii. impaired glucose tolerance (2 h PG ≥7.8 mmol/L) iii. type 2 diabetes (no medication, HbA1c ≤7.5%)

  2. Or (controls): BMI 19-25 kg/m2 and normal glucose metabolism and no first degree relatives with type 2 diabetes.

Exclusion Criteria:

1. Subjects having type 1 diabetes or medically treated type 2 diabetes.
2. Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 90 mmHg at screening
3. Significant hematological or renal disease or chronic renal impairment, GFR< 50 ml/min.
4. Significant liver disease or ALAT >3x UNL.
5. Chronic inflammatory disease in active phase or long-term use of corticosteroids last 3 months.
6. Use of anti-diabetic agents, lipid lowering drugs, antihypertensive medication, ASA or any other drug not deemed suitable by the study physician.
7. Mental condition (psychiatric or organic cerebral disease), drug or alcohol abuse rendering the subject unable to understand the nature, scope and possible consequences of the study.
8. BMI outside inclusion criteria.
9. Smoker
10. Any medical or other condition that in the judgment of the investigator would jeopardize the subject's safety or evaluation of the intervention for efficacy and safety
11. Exercising regularly (>1 times pr week)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise in normoglycaemic individuals	Other: Exercise; 12 weeks of exercise; 4 times pr week
Experimental: Exercise in hyperglycaemic individuals	Other: Exercise; 12 weeks of exercise; 4 times pr week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in gene expression changes in skeletal and adipose tissue	Baseline and after 12 weeks, and before, 0 hr and 2 hours after acute exercise
Changes from baseline in plasma/serum levels of selected proteins	Baseline and after 12 weeks, and before, 0 hr and 2 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in insulin sensitivity	Insulin sensitivity will be measured using the euglycaemic hyperinsulinaemic clamp technique.	Before and after 12 weeks of exercise
Changes in baseline from maximal oxygen uptake VO2 max		Before and after 12 weeks
Changes from baseline in muscle strength		Before and after 12 weeks
Changes from baseline in body composition	Body composition will be estimated with whole body MRI.	Before and after 12 weeks
Changes from baseline in heart frequency		Before and after 12 weeks

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: University of Oslo; Norwegian School of Sport Sciences
• Investigators: Principal Investigator: Kåre I Birkeland, MD PhD, Oslo University Hospital; Study Chair: Christian A Drevon, MD PhD, University of Oslo

Publications and helpful links

General Publications

• Moore TM, Zhou Z, Cohn W, Norheim F, Lin AJ, Kalajian N, Strumwasser AR, Cory K, Whitney K, Ho T, Ho T, Lee JL, Rucker DH, Shirihai O, van der Bliek AM, Whitelegge JP, Seldin MM, Lusis AJ, Lee S, Drevon CA, Mahata SK, Turcotte LP, Hevener AL. The impact of exercise on mitochondrial dynamics and the role of Drp1 in exercise performance and training adaptations in skeletal muscle. Mol Metab. 2019 Mar;21:51-67. doi: 10.1016/j.molmet.2018.11.012. Epub 2018 Dec 4.
• Lee S, Norheim F, Gulseth HL, Langleite TM, Aker A, Gundersen TE, Holen T, Birkeland KI, Drevon CA. Skeletal muscle phosphatidylcholine and phosphatidylethanolamine respond to exercise and influence insulin sensitivity in men. Sci Rep. 2018 Apr 25;8(1):6531. doi: 10.1038/s41598-018-24976-x. Erratum In: Sci Rep. 2018 May 15;8(1):7885.
• Sommer C, Lee S, Gulseth HL, Jensen J, Drevon CA, Birkeland KI. Soluble Leptin Receptor Predicts Insulin Sensitivity and Correlates With Upregulation of Metabolic Pathways in Men. J Clin Endocrinol Metab. 2018 Mar 1;103(3):1024-1032. doi: 10.1210/jc.2017-02126.
• Lee S, Norheim F, Langleite TM, Noreng HJ, Storas TH, Afman LA, Frost G, Bell JD, Thomas EL, Kolnes KJ, Tangen DS, Stadheim HK, Gilfillan GD, Gulseth HL, Birkeland KI, Jensen J, Drevon CA, Holen T; NutriTech Consortium. Effect of energy restriction and physical exercise intervention on phenotypic flexibility as examined by transcriptomics analyses of mRNA from adipose tissue and whole body magnetic resonance imaging. Physiol Rep. 2016 Nov;4(21):e13019. doi: 10.14814/phy2.13019.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: February 26, 2013
• First Submitted That Met QC Criteria: March 1, 2013
• First Posted (Estimate): March 4, 2013

Study Record Updates

• Last Update Posted (Estimate): March 4, 2013
• Last Update Submitted That Met QC Criteria: March 1, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Exercise; Insulin sensitivity; Skeletal muscle; Myokine
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia
• Other Study ID Numbers: 2011/882