Composition & Function of Sarcoplasmic Reticulum in Persons With the Metabolic Syndrome
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 2/7/2018 |
| Start Date: | March 2014 |
| End Date: | December 2019 |
Modulating Physiologic Effects Of Phospholipid Metabolism In Obesity And Diabetes; AIM 4: Composition and Function of Sarcoplasmic Reticulum in Persons With the Metabolic Syndrome
The investigators previous research has suggested that lipid (fatty) composition in the
muscle cells of mice plays a key role in their insulin sensitivity. The purpose of this study
is to determine whether these specific fat signatures translate to humans by comparing the
muscle of healthy patients to those with pre-diabetes, or "the metabolic syndrome".
muscle cells of mice plays a key role in their insulin sensitivity. The purpose of this study
is to determine whether these specific fat signatures translate to humans by comparing the
muscle of healthy patients to those with pre-diabetes, or "the metabolic syndrome".
The Comp-SR study explores the role of lipid metabolism in key metabolic pathways in skeletal
muscle. It is a translation of previous research done in mice studying the effects and
functions of certain key enzymes involved in lipid metabolism found to be associated with
insulin resistance. These enzymes are fatty acid synthase (FAS), choline/ethanolamine
phosphotransferase 1 (CEPT1) and sarcoplasmic-endoplasmic reticulum ATPase (SERCA). Based on
the investigators research, it appears that the activity and function of these enzymes
determines the ratio of certain phospholipids in the sarcoplasmic reticulum (SR), namely
phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Furthermore, the investigators
have found that the ratio of these phospholipids correlates with the mouse's sensitivity to
insulin.
Based on the muscle biopsies of four healthy persons, it was found that human muscle contains
similar phospholipids and phospholipid ratios to mice. It is hypothesized that these
phospholipid signatures may be predictive of the metabolic status of humans as well. The
specific aims of this study are to determine if the composition and function of the
sarcoplasmic reticulum is altered in persons with the metabolic syndrome compared to lean
controls. This knowledge could provide new understanding of impediments to effective therapy,
novel biomarkers of disease progression, and innovative treatment targets for diabetes.
muscle. It is a translation of previous research done in mice studying the effects and
functions of certain key enzymes involved in lipid metabolism found to be associated with
insulin resistance. These enzymes are fatty acid synthase (FAS), choline/ethanolamine
phosphotransferase 1 (CEPT1) and sarcoplasmic-endoplasmic reticulum ATPase (SERCA). Based on
the investigators research, it appears that the activity and function of these enzymes
determines the ratio of certain phospholipids in the sarcoplasmic reticulum (SR), namely
phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Furthermore, the investigators
have found that the ratio of these phospholipids correlates with the mouse's sensitivity to
insulin.
Based on the muscle biopsies of four healthy persons, it was found that human muscle contains
similar phospholipids and phospholipid ratios to mice. It is hypothesized that these
phospholipid signatures may be predictive of the metabolic status of humans as well. The
specific aims of this study are to determine if the composition and function of the
sarcoplasmic reticulum is altered in persons with the metabolic syndrome compared to lean
controls. This knowledge could provide new understanding of impediments to effective therapy,
novel biomarkers of disease progression, and innovative treatment targets for diabetes.
Control subjects
Inclusion:
- <15 min exercise per day, <2 days per week
- Age >18 and <65
- Body Mass Index (BMI) <25
- Healthy by physical exam (patient is devoid of major acute or chronic illness)
- No significant abnormality in screening labs
Exclusion:
- Currently on any significant prescription medications other than oral contraceptives
in women
- Currently Pregnant
- Current Tobacco Use
Subjects with the Metabolic Syndrome
Inclusion:
- <15 min exercise per day, <2 days per week
- Age >18 and <65
- Body Mass Index (BMI) >30
- Meet at least three of the following Adult Treatment Panel (ATP) III criteria for the
metabolic syndrome:
- waist circumference > or = 40 inches in men, > or = 35 inches in women
- blood triglycerides > or = 150 mg/dL
- blood HDL cholesterol <40 mg/dL in men, <50 in women
- blood pressure > or = 130 mmHg systolic, or > or = 85 mmHg diastolic
- fasting blood sugar > or = 100 mg/dL
Exclusion:
- Diagnosed with Type 2 diabetes, coronary artery disease, cancer, liver, lung, or
kidney disease or any other major illness
- Currently on any significant prescription medications other than:
- oral contraceptives in women
- More than two standard medication for stage 1 hypertension in men or women (blood
pressure 140-159/90-99)
- Currently Pregnant
- Current Tobacco Use
We found this trial at
1
site
660 S Euclid Ave
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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