Physiologic and Functional Adaptations of Insulin Sensitive Tissues

Summary

The long-term goal is to understand the mechanisms of intestinal nutrient sensing and signal relays to insulin sensitive tissues (adipose, skeletal muscle, liver) in humans. The investigators hypothesize that human tissue biopsies (from obese surgery and non-surgery subjects as well as lean controls) can be used to understand the molecular mechanisms underlying intestinal nutrient sensing and signal relay in humans. The investigator will obtain tissue specimens from patients during scheduled upper endoscopies, colonoscopies and scheduled metabolic and bariatric surgeries or liver transplantation. A blood sample (4mL) will be obtained concurrent with these procedures. From metabolic and bariatric surgery subjects blood and tissues (liver, adipose, small intestine, omentum, skeletal muscle) can be collected at the time of surgery. From liver transplantation patients, excised liver tissue will be collected. Stool can be obtained preoperatively and at various time points after surgery. Some bariatric surgery subjects will participate in a mixed-meal tolerance test at their pre-operative visit and several post-operative visits to compare the whole-body metabolic alterations following bariatric procedures.

Conditions

• Diabetes
• Insulin Resistance
• Obesity
• Bariatric Surgery Candidate
• Roux-en-y Gastric Bypass
• Liver Diseases

Interventions

OTHER

Endoscopy biopsy

Tissue samples will be collected from the jejunum, duodenum, and colon during the subject's standard of care procedure.

OTHER

Surgical biopsy

Biopsy of the liver is standard of care for diagnosing NAFLD. Biopsy of omentum, skeletal muscle and subcutaneous adipose (the latter two tissues taken at the site of trocar placement) will be collected intraoperatively at the time of Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG).

OTHER

Mixed-meal tolerance test

The mixed meal tolerance test (MMTT) shows how much insulin your body is making after drinking a liquid meal beverage that contains fats, protein and carbohydrates (sugar). Glucose, C-peptide, free fatty acids, triglycerides, incretins, pancreatic polypertide, bile aceis, and fatty acid amides can also be measured. A total of 9 tablespoons of blood is taken over a 255 minute period.

OTHER

Excised Liver Tissue Sampling

Tissue will be collected from the excised liver for research after the diseased liver has been removed as part of the standard of care procedure.

Sponsors & Collaborators

• Vanderbilt University Medical Center

  lead OTHER

Principal Investigators

• Charles Flynn, Ph.D. · Vanderbilt University Medical Center

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-02-13

Primary Completion

2028-02-29

Completion

2028-02-29

Countries

• United States

Study Locations