Home
Search
Study Topics
Glossary
|
|
|
|
|
|
Sponsored by: |
Department of Veterans Affairs |
---|---|
Information provided by: | Department of Veterans Affairs |
ClinicalTrials.gov Identifier: | NCT00330967 |
The Objectives of the study are to: (1)compare the inflammatory response and insulin resistance in skeletal muscles during a systemic infusion of lipid with that during a local infusion of lipid into the femoral artery. which would cause minimal or no systemic hyperlipidemia but local plasma free fatty acid (FFA) concentrations similar to those during the systemic lipid infusion, and (2) determine the inflammatory response and insulin resistance in skeletal muscle during an infusion of lipid into the femoral artery as described above after NP-KB inhibition by high dose salicylate treatment in humans.
Condition | Intervention |
---|---|
Inflammation Insulin Resistance |
Drug: 20% Intralipid Drug: Salicylate |
Study Type: | Observational |
Study Design: | Prospective |
Official Title: | Mechanisms of Insulin Resistance in Humans |
Blood samples, muscle biopsies
Estimated Enrollment: | 32 |
Study Start Date: | April 2006 |
Estimated Study Completion Date: | December 2009 |
Estimated Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
Groups/Cohorts | Assigned Interventions |
---|---|
1
healthy subjects
|
Drug: 20% Intralipid
lipid infusion
|
2
healthy subjects different from group 1
|
Drug: 20% Intralipid
lipid infusion
Drug: Salicylate
treatment with anti-inflammatory agent
|
Insulin resistance in skeletal muscle is a characteristic abnormality in obesity and the metabolic syndrome and a major factor responsible for the development of type 2 diabetes. Although the mechanisms responsible for muscle insulin resistance are largely unclear, lipid oversupply is an important factor. Among numerous potential mechanisms whereby lipid oversupply may cause muscle insulin resistance, current evidence points towards inflammation as being critical. Recent studies in animals, however, indicate that the inflammatory response in skeletal muscles may require the presence of circulating pro-inflammatory factors suggesting that the inflammation induced insulin resistance in skeletal muscles may be a secondary event. More specifically, activation of Nuclear Factor-Kappa B(NF-kB), and inflammatory master switch that drives the production of numerous pro-inflammatory cytokines in fat and liver, has been implicated in causing insulin resistance in skeletal muscles by increasing circulating pro-inflammatory cytokines. In contrast, animal studies have found that activation of NP-KB directly in skeletal muscles has no or little effect on its insulin sensitivity but does produce other abnormalities such as increased proteasome activity. The study shall therefore be undertaken to determine to what extent lipid-induced inflammation and insulin resistance in skeletal muscles requires the presence of circulating proinflammatory factors in humans.
Ages Eligible for Study: | 21 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
healthy subjects
Inclusion Criteria:
- two groups of 16 healthy subjects
Exclusion Criteria:
Contact: Donald L Gates, PhD | (602) 277-5551 ext 6918 | donald.gates2@va.gov |
United States, Arizona | |
Carl T. Hayden VA Medical Center | Recruiting |
Phoenix, Arizona, United States, 85012 | |
Contact: Donald L Gates, PhD 602-277-5551 ext 6918 donald.gates2@va.gov | |
Principal Investigator: Christian Meyer, MD |
Principal Investigator: | Christian Meyer, MD | Carl T. Hayden VA Medical Center |
Responsible Party: | Department of Veterans Affairs ( Meyer, Christian - Principal Investigator ) |
Study ID Numbers: | ENDA-029-05F |
Study First Received: | May 26, 2006 |
Last Updated: | October 30, 2008 |
ClinicalTrials.gov Identifier: | NCT00330967 |
Health Authority: | United States: Federal Government |
Fat Emulsions, Intravenous Free Fatty Acids Glucose Clamp Technique Inflammation |
Insulin Resistance Muscle, Skeletal NF-Kappa B Salicylates |
Hyperinsulinism Metabolic Diseases Salicylates Insulin Resistance |
Metabolic disorder Glucose Metabolism Disorders Insulin Inflammation |
Anti-Inflammatory Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Cyclooxygenase Inhibitors Enzyme Inhibitors Pharmacologic Actions Pathologic Processes Analgesics, Non-Narcotic |
Sensory System Agents Therapeutic Uses Anti-Inflammatory Agents, Non-Steroidal Analgesics Peripheral Nervous System Agents Antirheumatic Agents Central Nervous System Agents |