Mechanisms of Insulin Resistance in Humans

Inflammation Clinical Trial

Official title:

Mechanisms of Insulin Resistance in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00330967
• Other study ID #: ENDA-029-05F
• Status: Completed
• Phase: N/A
• First received: May 26, 2006
• Last updated: March 17, 2015
• Start date: April 2006
• Est. completion date: August 2014

Study information

• Verified date: March 2015
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: August 2014
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

• two groups of 16 healthy subjects

Exclusion Criteria:

• diabetes or impaired glucose tolerance

• peripheral vascular disease

• pulmonary disease

• clinically significant hepatic or renal disease

• triglycerides >200mg/dl

• anemia

• abnormal PT, PTT or INR

• pregnancy or lactation

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Inflammation
• Insulin Resistance

Intervention

Drug:
• 20% Intralipid
lipid infusion

Locations

Country	Name	City	State
United States	Phoenix VA Health Care System Carl T. Hayden VA Medical Center, Phoenix, AZ	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Signaling With Lipid Infusion	IRS-1 expression in response to femoral lipid infusion in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blot bands, normalized to a housekeeping protein, GAPDH, in control and treated groups.	4 h	No
Primary	Phos-p38 MAPK Expression With Femoral Lipid and Insulin Infusions	Phosphorylation of p38 MAPK in response to femoral lipid and insulin infusions. phospho-p38 MAPK expression in response to femoral lipid infusion in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.	4 h	No
Primary	p38 MAPK Expression With Femoral Lipid and Insulin Infusions	p38 MAPK expression in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.	4 h	No
Primary	Phospho-ERK MAPK Expression With Femoral Lipid and Insulin Infusions	Phosphorylation of ERK MAPK in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.	4 h	No
Primary	ERK MAPK Expression With Femoral Lipid and Insulin Infusions	ERK MAPK expression in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.	4 h	No
Primary	Phospho-JNK MAPK Expression With Femoral Lipid and Insulin Infusions	Phosphorylation of JNK MAPK in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.	4 h	No
Primary	JNK MAPK Expression With Femoral Lipid and Insulin Infusions	JNK MAPK expression in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.	4 h	No