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Mechanism of Fatty Acid-Induced Impairment of Glucose-Stimulated Insulin Secretion

NCT00188773 · Status: COMPLETED · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 15

Last updated 2008-06-05

No results posted yet for this study

Summary

A prolonged elevation of plasma free fatty acids (FFA) impairs glucose stimulated insulin secretion. The concept of fatty acid impairment of glucose stimulated insulin secretion (lipotoxicity) has now been well accepted. Increased free fatty acid flux from adipose tissue to non-adipose tissue, resulting from abnormalities of fat metabolism, participates in and amplifies many of the metabolic derangements that are characteristic of insulin resistance syndrome and type 2 diabetes.

Lipotoxicity is also likely to play an important role in the progression from normal glucose tolerance to fasting hyperglycemia and conversion to frank type 2 diabetes in insulin resistant individuals. This area of research is now focused on determining the mechanisms whereby FFAs impair b-cell function. There is some evidence to suggest that lipotoxicity could be mediated through induction of reactive oxygen species (ROS). N-acetylcysteine (NAC) is a known potent antioxidant and has been used experimentally in a number of medical conditions in humans for its protective antioxidant effects. The investigators now plan to administer NAC orally to humans for 48 hours to examine the effects of antioxidant therapy in ameliorating the deleterious effects of FFAs on pancreatic beta cell function. NAC is currently approved for the treatment of acetaminophen overdose and is also used as a mucolytic agent. The investigators are now using NAC as an antioxidant to determine whether it protects the pancreatic beta cell against the toxic effects of FFAs, as outlined in the detailed study protocol. This is a proof-of-principle study and is not designed to develop n-acetylcysteine for therapeutic use.

Conditions

  • Insulin Resistance Syndrome X
  • Pancreatic Beta Cell Function

Interventions

DRUG

N-acetylcysteine, intralipid, heparin

One visit subject will receive N-acetylcysteine plus intralipid and heparin, another visit n-acetylcyksteine plus saline, another visit intralipid and heparin and another visit saline alone

Sponsors & Collaborators

  • University Health Network, Toronto

    lead OTHER

Principal Investigators

  • Gary F. Lewis, MD · University Health Network, Toronto

Study Design

Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
35 Years
Max Age
65 Years
Sex
MALE
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2004-01-31
Primary Completion
2007-08-31
Completion
2008-01-31

Countries

  • Canada

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00188773 on ClinicalTrials.gov