Potential Association of a Common L-FABP Polymorphism With Lipid-induced Hepatic Insulin Resistance

May 3, 2012 updated by: German Institute of Human Nutrition
The investigators hypothesise that a common A277G polymorphism of the liver fatty acid binding protein (L-FABP) gene, which leads to an amino acid exchange, may be associated with alterations of lipid-induced hepatic insulin resistance. In the present study the investigators will investigate potential differences in lipid-induced hepatic insulin resistance, and in the relation between glycogenolysis and gluconeogenesis, in healthy subjects with the A277G polymorphism vs. subjects carrying the wildtype.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Liver fatty acid binding protein (L-FABP) is an abundant cytosolic lipid-binding protein that regulates lipid transport and metabolism. Only one common non-synonymous polymorphism (A227G) leading to an amino-acid exchange in the exonic region of the L-FABP gene has been previously identified. Experimental elevations of free fatty acids (FFAs) have been shown to impair insulin mediated suppression of endogenous glucose production (EGP). Deletion of the L-FABP gene shows no obvious phenotype in mice receiving a low fat chow diet, but leads to decreased hepatic triglyceride accumulation in the prolonged fasted state, which exposes mice to an increased fatty acid flux to the liver. The function of the L-FABP gene may be altered by polymorphisms in coding regions of the gene, probably leading to modifications in hepatic triglyceride accumulation and hepatic insulin resistance.We hypothesize that carriers of the A277G SNP, when compared to matched wild-type subjects, may show altered responses of hepatic glucose production upon exposure to increased peripheral fatty acid concentrations, as achieved by lipid / heparin infusions. Because it is known that free fatty acids potently increase insulin secretion, we use somatostatin clamps in our experiments, followed by replacement of postabsorptive insulin and glucagon concentrations.

Study Type

Interventional

Enrollment

18

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Nuthetal, Germany, 14558
        • German Institute of Human Nutrition DIfE, Dpt. of Clinical Nutrition, Potsdam-Rehbrücke

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • healthy subjects with normal glucose tolerance (NGT)

Exclusion Criteria:

  • any severe cardiac, liver, or kidney diseases
  • pregnant or lactating women, menstrual irregularities
  • cortisone, antidiabetic drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure
lipid-induced hepatic insulin resistance(WT vs.SNP L-FABP)
changes in the relation GNG to GL

Secondary Outcome Measures

Outcome Measure
changes in peripheral plasma glucose and lipid responses

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German Institute of Human Nutrition

Investigators

  • Principal Investigator: Martin O Weickert, MD, German Institute of Human Nutrition; Charité Campus Benjamin Franklin
  • Principal Investigator: Matthias Möhlig, MD, German Institute of Human Nutrition; Charité Campus Benjamin Franklin
  • Study Chair: Andreas FH Pfeiffer, MD, German Institute of Human Nutrition; Charité Campus Benjamin Franklin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Study Completion

April 1, 2006

Study Registration Dates

First Submitted

January 12, 2006

First Submitted That Met QC Criteria

January 12, 2006

First Posted (Estimate)

January 16, 2006

Study Record Updates

Last Update Posted (Estimate)

May 4, 2012

Last Update Submitted That Met QC Criteria

May 3, 2012

Last Verified

August 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MOW_MM_LFABP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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