Ceramides in Muscle During Insulin Resistance
Withdrawn before enrolling
Conditions studied: Insulin Resistance
In brief
Overnutrition and physical inactivity promote the accumulation of sphingolipids such as ceramides which block insulin signaling and anabolic metabolism. Implementation of pharmacological or genetic interventions to reduce sphingolipid levels in rodents prevents or reverses an impressive array of metabolic pathologies (e.g. insulin resistance, diabetes, steatohepatitis, hypertension, cardiomyopathy, and atherosclerosis). To elucidate the tissue-specific mechanisms through which ceramides contribute to these diseases, mice have been produced to allow for the conditional, cell-type restricted ablation of enzymes required for ceramide biosynthesis or degradation (i.e. serine palmitoyltransferase and dihydroceramide desaturases-1) or degradation (i.e. acid ceramidase). Aims of the project include the following: To use these novel mouse models to evaluate the effect of muscle-specific ceramide depletion or induction on insulin sensitivity, muscle growth, and genomic/proteomic signatures under conditions of overnutrition and inactivity. To apply a ceramide flux assay in isolated human myotubes to identify the regulatory mechanisms that influence rates of ceramide biosynthesis; and, To determine the efficacy of a new class of inhibitors of dihydroceramide desaturases-1, our preferred target in the ceramide synthesis pathway, as therapeutics that improve muscle insulin sensitivity and prevent muscle loss in rodents. Findings obtained from these studies could uncover new nutrient-sensing machinery that modulates insulin sensitivity and muscle growth. Moreover, the translational component could lead to new pharmacological approaches for improving muscle health.
Key facts
- Study ID
- NCT03731598
- Run by
- University of Utah
- People needed
- 0
- Starts
- 2018-05-01
- Expected to finish
- 2022-01-01
- Last updated by the study team
- 2022-06-22
Who can join
Age: 60 and older. Sex: any. Healthy volunteers: accepted.
You may qualify if…
- Age between 60 yrs and older
- Ability to sign informed consent
- Free-living, prior to admission
You may not qualify if…
- Cardiac abnormalities considered exclusionary by the study physician
- Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
- Globular filtration rate <65 mL/min/1.73m2 or evidence of kidney disease or failure
- Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes, hypercholesterolemia > 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal and pedal arteries)
- Risk of deep vein thrombosis including family history of thrombophilia, deep vein thrombosis, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis (platelets>400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocysteinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombin III
- Use of anticoagulant therapy (e.g., Coumadin, heparin)
- Elevated systolic pressure >150 or a diastolic blood pressure > 100
- Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
- Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
- Inability to abstain from smoking for duration of study
- A history of > 20 pack per year smoking
- HIV or hepatitis B or C
- Recent anabolic or corticosteroids use (within 3 months)
- Subjects with hemoglobin or hematocrit lower than accepted lab values
- Agitation/aggression disorder (by psychiatric history and exam)
- History of stroke with motor disability
- A recent history (<12 months) of gastrointestinal bleed
- Liver disease
- Respiratory disease (acute upper respiratory infection, history of chronic lung disease with resting oxygen saturation <97% on room air)
- Any other condition or event considered exclusionary by the PI and faculty physician
Where it is running
- University of Utah — Salt Lake City, Utah, United States
- The University of Utah — Salt Lake City, Utah, United States
Full record on ClinicalTrials.gov
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