Genetic of Skeletal Muscle Insulin Resistance

In this study, we will use euglycemic/hyperinsulinemic clamps, longitudinal skeletal muscle biopsies, and single nucleus RNA- and ATAC- sequencing to reveal cell type-specific molecular response Quantitative trait loci (rQTLs) acutely regulated by insulin signaling and glucose uptake.

Inclusion Criteria: * Males and Females Age 18-75 * Body Mass Index (BMI) \> 18 * Normal glucose tolerance as defined by: Fasting blood sugar \< 100 mg/dL 2-hour Oral Glucose Tolerance Test (OGTT) \< 140mg/dL Stable weight over the past 3 months defined as \>±5% change in body weight * Hemoglobin A1c \< 5.7 * Creatinine \< 2 * Aspartate aminotransferase/Alanine transaminase (AST/ALT) \< 75 * Blood sodium 135 to 145 mEq/L * Blood potassium 3.6 to 5.2 mmol/L\[MH1.1\] Exclusion Criteria: * Urine albumin excretion\>300mg/day * Partial thromboplastin time (PTT) \>35International normalized ratio (INR) \> 1.2 * No oral corticosteroids for 1 month * No Sodium-glucose co-transporter 2 (SGLT2) inhibitor for 3 months * No glucagon-like peptide-1 (GLP-1) receptor agonist for 6 months * Any anti-platelet or anti-coagulation medication other than as needed for Pain Management * No alcohol 4 days before the insulin clamp and biopsy procedure * No acute structural knee injuries * No Rheumatologic muscular or nervous system disease * Pregnancy, Intentions to become pregnant, or Breastfeeding * Blood Pressure \>170/110 * Temperature \> 100F * Triglycerides \> 400 by lipid panel * Hemoglobin \