NCT00330967

Mechanisms of Insulin Resistance in Humans

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 25 (actual)
• Sponsor: US Department of Veterans Affairs · Federal
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Accepted

Summary

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 NF-KB inhibition by high dose salicylate treatment in humans.

Detailed description

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 NF-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.

Conditions

• Inflammation
• Insulin Resistance

Interventions

Type	Name	Description
DRUG	20% Intralipid	lipid infusion

Timeline

• Start date: 2006-04-01
• Primary completion: 2012-01-01
• Completion: 2014-08-01
• First posted: 2006-05-29
• Last updated: 2015-04-03
• Results posted: 2015-03-17

Locations

1 site across 1 country: United States