Composition & Function of Sarcoplasmic Reticulum in Persons With the Metabolic Syndrome

Completed

Brief Summary: 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".

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Metabolic Syndrome	muscle biopsy	Muscle biopsy to determine sarcoplasmic reticulum composition and function, Oral Glucose tolerance test with insulin levels at time points to determine Insulin sensitivity, DEXA scan to determine lean muscle and fat mass
Control	muscle biopsy	Muscle biopsy to determine sarcoplasmic reticulum composition and function, Oral Glucose tolerance test with insulin levels at time points to determine Insulin sensitivity, DEXA scan to determine lean muscle and fat mass

Primary Outcome Measures

Name	Time	Method
Sarcoplasmic Reticulum Composition	Study Visit Week 4	We will take a muscle tissue sample from the subject's thigh (vastus lateralis) to quantify phosphatidylcholine to phosphatidylethanolamine ratio of the sarcoplasmic reticulum.

Secondary Outcome Measures

Name	Time	Method
Insulin Sensitivity	Study visit week 4	The homeostatic model assessment for insulin resistance (HOMA-IR) is a calculated value using fasting glucose and insulin levels. It provides a measure of insulin resistance. HOMA-IR values between 0.5 and 1.4 are considered normal and values \>2.9 indicate insulin resistance. The Matsuda Index reflects insulin sensitivity. It is calculated from glucose and insulin levels drawn fasting and during an OGTT. Matsuda Index values of 2.5 or higher are normal and indicate lack of insulin resistance or normal insulin sensitivity. Results of these measures are displayed graphically in the published paper.
Lean and Fat Body Mass	Study Visit week 4	We will perform a Duel Energy X-ray absorptiometry (DEXA) scan to approximate lean and fat body mass of study subjects.

Locations (1): Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States