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

Sponsor

German Institute of Human Nutrition (Other)

Overall Status

Completed

CT.gov ID

NCT00277342

Collaborator

(none)

Enrollment

Location

Duration (Months)

6.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Wildtype Polymorphism Liver FABP	Procedure: measurement of lipid-induced hepatic insulin resistance	N/A

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 Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Single

Primary Purpose:

Diagnostic

Study Start Date :

Jan 1, 2006

Study Completion Date :

Apr 1, 2006

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

changes in peripheral plasma glucose and lipid responses []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	German Institute of Human Nutrition DIfE, Dpt. of Clinical Nutrition, Potsdam-Rehbrücke	Nuthetal		Germany	14558

Sponsors and Collaborators

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