The Suppression of Toll Like Receptors by Insulin

Not Applicable

Completed

• Conditions: Insulin Resistance
• Interventions: Drug: insulin infusion; Drug: Dextrose infusion; Drug: Saline Infusion

• Registration Number: NCT01151605
• Lead Sponsor: University at Buffalo

Brief Summary

This study will help us understand the possible beneficial effects of insulin in inflammation. Inflamamtion is considered to be the cause of atherosclerosis and heart disease.

Detailed Description

Obesity and type 2 diabetes are major health problems in the United States and the world. Both conditions are characterized by increased inflammation and oxidative stress and are associated with increased risk of cardiovascular disease.

Our previous work shows that insulin exerts a prompt and powerful anti-inflammatory effect, on circulating blood cells and in plasma in healthy subjects and in critically ill patients.

Toll like receptors (TLRs) recognize bacterial and viral products like endotoxin and viruses and are major determinants of the inflammatory response against foreign pathogens. In view of the recent data showing that TLRs recognize a range of molecules and proteins that are not of pathogenic source like saturated lipids and that TLRs are involved in the pathogenesis of atherosclerosis which leads to cardiovascular disease and insulin resistance which leads to type 2 diabetes (DM) we hypothesized that insulin infusion suppresses TLRs expression.

Our preliminary data show that insulin infusion for 4 hours reduces the levels of many TLRs and thus might protect from inflammation induced conditions We therefore propose to investigate, in more detail, the effect of infusing different doses of insulin on TLRs mRNA and protein levels and its activity in obese and DM subjects over a longer infusion period and a larger number of subjects in circulating white blood cells and in fat tissue. Also we will be comparing the baseline levels of TLRs and TLRs related proteins as well as their modulation by insulin between normal, obese and DM subjects.

Study Timeline

• Study Start: 2008-09
• Study First Submitted: 2010-06-25
• Study First Submitted QC: 2010-06-25
• Study First Posted: 2010-06-28
• Primary Completion: 2013-09
• Study Completion: 2013-12
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-01
• Last Update Posted: 2024-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
obese subjects	Dextrose infusion	obese (BMI \>30Kg/m2) subjects infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr
Normal weight subjects	Dextrose infusion	Normal weight subjects infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr
obese type 2 diabetes subjects	Saline Infusion	obese (BMI \>30Kg/m2) subjects with type 2 diabetes infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr
obese type 2 diabetes subjects	insulin infusion	obese (BMI \>30Kg/m2) subjects with type 2 diabetes infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr
obese subjects	insulin infusion	obese (BMI \>30Kg/m2) subjects infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr
obese subjects	Saline Infusion	obese (BMI \>30Kg/m2) subjects infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr
Normal weight subjects	insulin infusion	Normal weight subjects infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr
Normal weight subjects	Saline Infusion	Normal weight subjects infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr
obese type 2 diabetes subjects	Dextrose infusion	obese (BMI \>30Kg/m2) subjects with type 2 diabetes infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr

Primary Outcome Measures

Name	Time	Method
The Suppression of Toll Like receptors by Insulin	24 hours	Expression of TLR2, TLR4, TLR7 and TLR9 mRNA in mononuclear cells and adipose tissue

Secondary Outcome Measures

Name	Time	Method
TLR expression	0 hours	Basal TLR expression in obese and type 2 diabetic subjects as compared to lean subjects

Trial Locations

Locations (1)

Millard Fillmore Gates Hospital; 🇺🇸 Buffalo, New York, United States