Potential Association of a Common L-FABP Polymorphism With Lipid-Induced Hepatic Insulin Resistance
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Purpose
click on markers to display additional informationThe 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.
status: completed conditions: Wildtype ; Polymorphism Liver FABP interventions: measurement of lipid-induced hepatic insulin resistance phase: N/A study type: Interventional study design: Diagnostic, Randomized, Single Blind, Placebo Control, Single Group Assignment -
Further study details (as provided by German Institute of Human Nutrition)
primary outcome measures:
secondary outcome measures:
- changes in peripheral plasma glucose and lipid responses
enrollment: 18
study start date: January 2006
study completion date: April 2006
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.
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Eligibility
ages eligible for study: 18 Years to 70 Years genders eligible for study: Both Criteria
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Contacts and locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00277342
Locations
Germany - German Institute of Human Nutrition DIfE, Dpt. of Clinical Nutrition, Potsdam-Rehbrücke
facility: Nuthetal, Germany, 14558
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Sponsors and collaborators
German Institute of Human Nutrition
investigators: Martin O Weickert, MD, Principal Investigator, German Institute of Human Nutrition; Charité Campus Benjamin Franklin
Matthias Möhlig, MD, Principal Investigator, German Institute of Human Nutrition; Charité Campus Benjamin Franklin
Andreas FH Pfeiffer, MD, Study Chair, German Institute of Human Nutrition; Charité Campus Benjamin Franklin
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More information
German Institute of Human Nutrition
Publication list: Department of Endocrinology, Diabetes and Nutrition, Charité-University-Medicine Berlin
Publications of results
first received: January 12, 2006 last updated: August 6, 2008 ClinicalTrials.gov Identifier: NCT00277342 health authority: Germany: Ethics Commission
Information obtained from ClinicalTrials.gov on September 25, 2009 Link to the current ClinicalTrials.gov record.
