No subject was involved in strenuous physical activity and had a stable body weight (±2%) for at least 3 months before the study. Volunteers were excluded if they had a Ceritinib chemical structure history of alcohol abuse (≥20

g/day); liver disease other than NASH (hepatitis B or C, autoimmune hepatitis, hemochromatosis, Wilson disease, drug-induced disease, other); type 1 diabetes; or a history of clinically significant renal, pulmonary, or heart disease (New York Heart Classification greater than grade II). The study was approved by the UTHSCSA Institutional Review Board, and informed written consent was obtained from each patient prior to participation. All studies were performed at the Frederic C. Bartter Clinical Research Unit (except liver imaging, which was performed at the UTHSCSA Research Imaging Center, and liver biopsy, which was performed at the VA Radiology Department). Baseline metabolic DNA Damage inhibitor measurements included: (1) fasting plasma glucose, A1c, lipid profile, liver function tests, insulin, free fatty acid (FFA); (2) whole body fat by dual energy x-ray absorptiometry (DXA); (3) hepatic fat content by MRS; (4) 75-g

oral glucose tolerance test to establish the diagnosis of normal glucose tolerance or diabetes according to American Diabetes Association criteria14; (5) euglycemic hyperinsulinemic clamp with 3-[3H] glucose to measure endogenous (primarily hepatic) and total body (largely muscle) insulin sensitivity15; (6) liver biopsy for histology to confirm the diagnosis of NASH and establish the stage and grade of the disease. Total body fat content was measured by DXA (Hologic Inc, Waltham, MA). For the measurement of hepatic fat content, localized 1H NMR spectra of the liver were acquired on a

Siemens TIM TRIO 3.0T MRI whole body scanner as described.13 In brief, two areas of interest were taken using an echo time/repetition time/angle of 30 milliseconds/2,000 milliseconds/90 degrees, and two liver this website areas with a volume of 30 × 30 × 30 mm were used. A liver fat content of >5.5% was considered diagnostic of NAFLD.12 Patients were admitted to the research unit at 6:30 AM after a 12-hour overnight fast, and the study was performed as reported by our group.16 In brief, upon arrival at the unit, a polyethylene catheter was inserted into an antecubital vein for infusion of all test substances. A second catheter was inserted retrogradely into an ipsilateral wrist vein on the dorsum of the hand for collection of arterialized blood sampling, and the hand was kept in a heated box at 65°C. A primed (25 μCi × [fasting glucose/100])–continuous (0.25 μCi/minute) infusion of 3-[3H] glucose (DuPont-NEN, Boston, MA) was initiated and continued until the end of the study.