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

NCT ID: NCT00277342

Last Updated: 2012-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2006-04-30

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.

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.

Conditions

Wildtype; Polymorphism Liver FABP

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Interventions

measurement of lipid-induced hepatic insulin resistance

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

German Institute of Human Nutrition

OTHER

Sponsor Role: lead

Principal Investigators

Martin O Weickert, MD

Role: PRINCIPAL_INVESTIGATOR

German Institute of Human Nutrition; Charité Campus Benjamin Franklin

Matthias Möhlig, MD

Role: PRINCIPAL_INVESTIGATOR

German Institute of Human Nutrition; Charité Campus Benjamin Franklin

Andreas FH Pfeiffer, MD

Role: STUDY_CHAIR

German Institute of Human Nutrition; Charité Campus Benjamin Franklin

Locations

German Institute of Human Nutrition DIfE, Dpt. of Clinical Nutrition, Potsdam-Rehbrücke

Nuthetal, , Germany

Countries

Germany

References

Weickert MO, Loeffelholz CV, Roden M, Chandramouli V, Brehm A, Nowotny P, Osterhoff MA, Isken F, Spranger J, Landau BR, Pfeiffer AF, Mohlig M. A Thr94Ala mutation in human liver fatty acid-binding protein contributes to reduced hepatic glycogenolysis and blunted elevation of plasma glucose levels in lipid-exposed subjects. Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E1078-84. doi: 10.1152/ajpendo.00337.2007. Epub 2007 Aug 14.

Reference Type: RESULT

PMID: 17698986 (View on PubMed)

Other Identifiers

MOW_MM_LFABP

Identifier Type: -

Identifier Source: org_study_id