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The Suppression of Toll Like Receptors by Insulin

2014-07-23 21:08:40 | BioPortfolio

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.

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 Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Conditions

Insulin Resistance

Intervention

insulin, insulin, insulin

Location

Millard Fillmore Gates Hospital
Buffalo
New York
United States
14209

Status

Recruiting

Source

Kaleida Health

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-07-23T21:08:40-0400

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Medical and Biotech [MESH] Definitions

A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.

Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. It can be caused by the presence of INSULIN ANTIBODIES or the abnormalities in insulin receptors (RECEPTOR, INSULIN) on target cell surfaces. It is often associated with OBESITY; DIABETIC KETOACIDOSIS; INFECTION; and certain rare conditions. (from Stedman, 25th ed)

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Insulin formulation containing substance which delays or retards time period of the absorption of insulin.

A preparation of insulin and zinc chloride in the form of a crystalline suspension. Typically the duration of ultralente insulin activity lasts between 18-30 hours after dosage.

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